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Th1133 details

Primary information
ID 1615
ThPP ID Th1133
Therapeutic Peptide/Protein Name Aflibercept
Sequence SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLI view full sequnce in fasta
Functional Classification Ib
Molecular Weight 115000
Chemical Formula C4318H6788N1164O1304S32
Isoelectric Point N.A.
Hydrophobicity N.A.
Melting Point (℃) N.A.
Half Life Intravitreal half life - 7.13 days
Description Aflibercept is a vascular endothelial growth factor (VEGF) inhibitor. It is a recombinant dimeric fusion glycoprotein that comprises (VEGF) binding portions from the extracellular domains of human VEGF receptors 1 and 2, this is fused to the Fc portion of human IgG1. It contains approximately 15% glycosylation to give a total molecular weight of 115 kDa (protein part = 96.9 kDa). It has 5 putative N-glycosylation sites on each polypeptide chain and the attached carbohydrates exhibit some degree of chain heterogeneity, including heterogeneity in terminal sialic acid residues, except at the site associated with the Fc domain, which is unsialylated.
Indication/Disease The opthalmic agent is used for the treatment of neovascular (wet) age-related mascular degeneration (AMD) and macular edema following central retinal vein occulsion (CRVO). The systemic injection, known as ziv-aflibercept, in combination with 5-fluorouracil, leucovorin, irinotecan-(FOLFIRI), is for the treatment of metastatic colorectal cancer that is resistant to or progressed following treatment with oxaliplatin.
Pharmacodynamics Compared to other anti-VEGF drugs like bevacizumab and ranibizumab, aflibercept has a higher binding affinity to VEGF-A (Kd = 0.5 pM).
Mechanism of Action Ablibercept is a recombinant fusion protein that acts as a decoy receptor for the ligands, vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PIGF). It prevents these ligands to binding to endothelial receptors, VEGFR-1 and VEGFR-2, to suppress neovascularization and decrease vascular permeability. This ultimately will slow vision loss or the progression of metastatic colorectal cancer.
Toxicity For all intravitreal VEGF inhibitors, there is increased risk of stroke and myocardial infarction. An increase in intraocular pressure may also occur. When used intravenously, most common adverse reactions were leukopenia, diarrhea, neutropenia, proteinuria, AST increased, stomatitis, fatigue, thrombocytopenia, ALT increased, hypertension, weight decreased, decreased appetite, epistaxis, abdominal pain, dysphonia, serum creatinine increased, and headache.
Metabolism Because aflibercept is a protein, it is expected to be broken down via proteolysis into smaller peptides and amino acids. The cytochrome P450 enzyme system is not involved in the metabolism of aflibercept.
Absorption In patients with wet AMD and CRVO, the mean peak plasma concentration (Cmax) was 0.02 mcg/mL and 0.05 mcg/mL respectively. These concentrations were reached in 1 to 3 days. Aflibercept did not accumulate when administered as repeated doses intravitreally every 4 weeks.
Volume of Distribution After Intravenous infusion of aflibercept, the volume of distribution is 6 L.
Clearance When cancer patients were given 2-9 mg/kg every 2 or 3 week; 1 hour IV infusion of aflibercept the typical estimated clearances were as follows:CL of free aflibercept (CLf) = 0.88 L/day;CL of bound aflibercept (CLf) = 0.19 L/day;Patients clear free aflibercept faster if they had low albumin or high alkaline phosphatase levels.
Categories Antineoplastic Agents and Ophthalmics
Patents Number US7306799
Date of Issue 26/03/09
Date of Expiry 24/05/24
Drug Interaction N.A.
Target Vascular endothelial growth factor A,Placenta growth factor,Vascular endothelial growth factor B
Information of corresponding available drug in the market
Brand Name Eylea
Company Regeneron Pharmaceuticals
Brand Discription EYLEA (aflibercept) is a recombinant fusion protein consisting of portions of human VEGF receptors 1 and 2 extracellular domains fused to the Fc portion of human IgG1 formulated as an iso-osmotic solution for intravitreal administration. Aflibercept is a dimeric glycoprotein with a protein molecular weight of 97 kilodaltons (kDa) and contains glycosylation, constituting an additional 15% of the total molecular mass, resulting in a total molecular weight of 115 kDa. Aflibercept is produced in recombinant Chinese hamster ovary (CHO) cells.
Prescribed for Neovascular (Wet) Age-Related Macular Degeneration (AMD), Macular Edema Following Central Retinal Vein Occlusion (CRVO)
Chemical Name N.A.
Formulation EYLEA is supplied as a preservative-free, sterile, aqueous solution in a single-use, glass vial designed to deliver 0.05 mL (50 microliters) of EYLEA (40 mg/mL in 10 mM sodium phosphate, 40 mM sodium chloride, 0.03% polysorbate 20, and 5% sucrose, pH 6.2).
Physcial Appearance EYLEA is a sterile, clear, and colorless to pale yellow solution.
Route of Administration Intravitreal Injection
Recommended Dosage The recommended dose for EYLEA is 2 mg (0.05 mL or 50 microliters) administered by intravitreal injection every 4 weeks (monthly) for the first 12 weeks (3 months), followed by 2 mg (0.05 mL) via intravitreal injection once every 8 weeks (2 months).
Contraindication ocular or periocular infections, active intraocular inflammation, Hypersensitivity
Side Effects Endophthalmitis and retinal detachments, Increased intraocular pressure, Thromboembolic events
Useful Link http://www.rxlist.com/eylea-drug.htm http://www.eylea.com/international/?p=/eylea-home/index.php http://www.drugs.com/eylea.html
PubMed ID 25646034, 25634529, 25632361, 25627086, 23673444, 23560774
3-D Structure Th1133 (View) or (Download)

Primary information
ID 1616
ThPP ID Th1133
Therapeutic Peptide/Protein Name Aflibercept
Sequence SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLI view full sequnce in fasta
Functional Classification Ib
Molecular Weight 115000
Chemical Formula C4318H6788N1164O1304S32
Isoelectric Point N.A.
Hydrophobicity N.A.
Melting Point (℃) N.A.
Half Life Intravitreal half life - 7.13 days
Description Aflibercept is a vascular endothelial growth factor (VEGF) inhibitor. It is a recombinant dimeric fusion glycoprotein that comprises (VEGF) binding portions from the extracellular domains of human VEGF receptors 1 and 2, this is fused to the Fc portion of human IgG1. It contains approximately 15% glycosylation to give a total molecular weight of 115 kDa (protein part = 96.9 kDa). It has 5 putative N-glycosylation sites on each polypeptide chain and the attached carbohydrates exhibit some degree of chain heterogeneity, including heterogeneity in terminal sialic acid residues, except at the site associated with the Fc domain, which is unsialylated
Indication/Disease The opthalmic agent is used for the treatment of neovascular (wet) age-related mascular degeneration (AMD) and macular edema following central retinal vein occulsion (CRVO). The systemic injection, known as ziv-aflibercept, in combination with 5-fluorouracil, leucovorin, irinotecan-(FOLFIRI), is for the treatment of metastatic colorectal cancer that is resistant to or progressed following treatment with oxaliplatin.
Pharmacodynamics Compared to other anti-VEGF drugs like bevacizumab and ranibizumab, aflibercept has a higher binding affinity to VEGF-A (Kd = 0.5 pM).
Mechanism of Action Ablibercept is a recombinant fusion protein that acts as a decoy receptor for the ligands, vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PIGF). It prevents these ligands to binding to endothelial receptors, VEGFR-1 and VEGFR-2, to suppress neovascularization and decrease vascular permeability. This ultimately will slow vision loss or the progression of metastatic colorectal cancer.
Toxicity For all intravitreal VEGF inhibitors, there is increased risk of stroke and myocardial infarction. An increase in intraocular pressure may also occur. When used intravenously, most common adverse reactions were leukopenia, diarrhea, neutropenia, proteinuria, AST increased, stomatitis, fatigue, thrombocytopenia, ALT increased, hypertension, weight decreased, decreased appetite, epistaxis, abdominal pain, dysphonia, serum creatinine increased, and headache.
Metabolism Because aflibercept is a protein, it is expected to be broken down via proteolysis into smaller peptides and amino acids. The cytochrome P450 enzyme system is not involved in the metabolism of aflibercept.
Absorption In patients with wet AMD and CRVO, the mean peak plasma concentration (Cmax) was 0.02 mcg/mL and 0.05 mcg/mL respectively. These concentrations were reached in 1 to 3 days. Aflibercept did not accumulate when administered as repeated doses intravitreally every 4 weeks.
Volume of Distribution After Intravenous infusion of aflibercept, the volume of distribution is 6 L.
Clearance When cancer patients were given 2-9 mg/kg every 2 or 3 week; 1 hour IV infusion of aflibercept the typical estimated clearances were as follows:CL of free aflibercept (CLf) = 0.88 L/day;CL of bound aflibercept (CLf) = 0.19 L/day;Patients clear free aflibercept faster if they had low albumin or high alkaline phosphatase levels.
Categories Antineoplastic Agents and Ophthalmics
Patents Number US7531173
Date of Issue 13/05/13
Date of Expiry 03/02/30
Drug Interaction N.A.
Target N.A.
Information of corresponding available drug in the market
Brand Name Zaltrap
Company Sanofi and Regeneron Pharmaceuticals, Inc.
Brand Discription Ziv-aflibercept is a recombinant fusion protein consisting of Vascular Endothelial Growth Factor (VEGF)-binding portions from the extracellular domains of human VEGF Receptors 1 and 2 fused to the Fc portion of the human IgG1. Ziv-aflibercept is produced by recombinant DNA technology in a Chinese hamster ovary (CHO) K-1 mammalian expression system. Ziv-aflibercept is a dimeric glycoprotein with a protein molecular weight of 97 kilodaltons (kDa) and contains glycosylation, constituting an additional 15% of the total molecular mass, resulting in a total molecular weight of 115 kDa.
Prescribed for metastatic colorectal cancer (mCRC) that is resistant to or has progressed following an oxaliplatin-containing regimen
Chemical Name N.A.
Formulation ZALTRAP is supplied in single-use vials of 100 mg per 4 ml and 200 mg per 8 ml formulated as 25 mg/mL ziv-aflibercept in polysorbate 20 (0.1%), sodium chloride (100 mM), sodium citrate (5 mM), sodium phosphate (5 mM), and sucrose (20%), in Water for Injection USP, at a pH of 6.2.
Physcial Appearance ZALTRAP is a sterile, clear, colorless to pale yellow, non-pyrogenic, preservative-free, solution for administration by Intravenous infusion.
Route of Administration Intravenous infusion
Recommended Dosage 4 mg per kg as an intravenous (IV) infusion over 1 hour every two weeks.
Contraindication N.A.
Side Effects Hemorrhage, Gastrointestinal, Compromised Wound Healing, Fistula Formation, Hypertension, Arterial Thromboembolic Events, Proteinuria, Neutropenia and Neutropenic Complications, Diarrhea and Dehydration, Reversible Posterior Leukoencephalopathy Syndrome
Useful Link http://www.rxlist.com/zaltrap-drug.htm http://www.zaltrap.com/ http://en.wikipedia.org/wiki/Aflibercept
PubMed ID 25646034, 25634529, 25632361, 25627086, 23673444, 23560774
3-D Structure Th1133 (View) or (Download)

Primary information
ID 1617
ThPP ID Th1133
Therapeutic Peptide/Protein Name Aflibercept
Sequence SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLI view full sequnce in fasta
Functional Classification Ib
Molecular Weight 115000
Chemical Formula C4318H6788N1164O1304S32
Isoelectric Point N.A.
Hydrophobicity N.A.
Melting Point (℃) N.A.
Half Life Intravitreal half life - 7.13 days
Description Aflibercept is a vascular endothelial growth factor (VEGF) inhibitor. It is a recombinant dimeric fusion glycoprotein that comprises (VEGF) binding portions from the extracellular domains of human VEGF receptors 1 and 2, this is fused to the Fc portion of human IgG1. It contains approximately 15% glycosylation to give a total molecular weight of 115 kDa (protein part = 96.9 kDa). It has 5 putative N-glycosylation sites on each polypeptide chain and the attached carbohydrates exhibit some degree of chain heterogeneity, including heterogeneity in terminal sialic acid residues, except at the site associated with the Fc domain, which is unsialylated
Indication/Disease The opthalmic agent is used for the treatment of neovascular (wet) age-related mascular degeneration (AMD) and macular edema following central retinal vein occulsion (CRVO). The systemic injection, known as ziv-aflibercept, in combination with 5-fluorouracil, leucovorin, irinotecan-(FOLFIRI), is for the treatment of metastatic colorectal cancer that is resistant to or progressed following treatment with oxaliplatin.
Pharmacodynamics Compared to other anti-VEGF drugs like bevacizumab and ranibizumab, aflibercept has a higher binding affinity to VEGF-A (Kd = 0.5 pM).
Mechanism of Action Ablibercept is a recombinant fusion protein that acts as a decoy receptor for the ligands, vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PIGF). It prevents these ligands to binding to endothelial receptors, VEGFR-1 and VEGFR-2, to suppress neovascularization and decrease vascular permeability. This ultimately will slow vision loss or the progression of metastatic colorectal cancer.
Toxicity For all intravitreal VEGF inhibitors, there is increased risk of stroke and myocardial infarction. An increase in intraocular pressure may also occur. When used intravenously, most common adverse reactions were leukopenia, diarrhea, neutropenia, proteinuria, AST increased, stomatitis, fatigue, thrombocytopenia, ALT increased, hypertension, weight decreased, decreased appetite, epistaxis, abdominal pain, dysphonia, serum creatinine increased, and headache.
Metabolism Because aflibercept is a protein, it is expected to be broken down via proteolysis into smaller peptides and amino acids. The cytochrome P450 enzyme system is not involved in the metabolism of aflibercept.
Absorption In patients with wet AMD and CRVO, the mean peak plasma concentration (Cmax) was 0.02 mcg/mL and 0.05 mcg/mL respectively. These concentrations were reached in 1 to 3 days. Aflibercept did not accumulate when administered as repeated doses intravitreally every 4 weeks.
Volume of Distribution After Intravenous infusion of aflibercept, the volume of distribution is 6 L.
Clearance When cancer patients were given 2-9 mg/kg every 2 or 3 week; 1 hour IV infusion of aflibercept the typical estimated clearances were as follows:CL of free aflibercept (CLf) = 0.88 L/day;CL of bound aflibercept (CLf) = 0.19 L/day;Patients clear free aflibercept faster if they had low albumin or high alkaline phosphatase levels.
Categories Antineoplastic Agents and Ophthalmics
Patents Number US7374758
Date of Issue 21/05/12
Date of Expiry 24/05/24
Drug Interaction N.A.
Target N.A.
Information of corresponding available drug in the market
Brand Name N.A.
Company N.A.
Brand Discription N.A.
Prescribed for N.A.
Chemical Name N.A.
Formulation N.A.
Physcial Appearance N.A.
Route of Administration N.A.
Recommended Dosage N.A.
Contraindication N.A.
Side Effects N.A.
Useful Link N.A.
PubMed ID 25646034, 25634529, 25632361, 25627086, 23673444, 23560774
3-D Structure Th1133 (View) or (Download)

Primary information
ID 1618
ThPP ID Th1133
Therapeutic Peptide/Protein Name Aflibercept
Sequence SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLI view full sequnce in fasta
Functional Classification Ib
Molecular Weight 115000
Chemical Formula C4318H6788N1164O1304S32
Isoelectric Point N.A.
Hydrophobicity N.A.
Melting Point (℃) N.A.
Half Life Intravitreal half life - 7.13 days
Description Aflibercept is a vascular endothelial growth factor (VEGF) inhibitor. It is a recombinant dimeric fusion glycoprotein that comprises (VEGF) binding portions from the extracellular domains of human VEGF receptors 1 and 2, this is fused to the Fc portion of human IgG1. It contains approximately 15% glycosylation to give a total molecular weight of 115 kDa (protein part = 96.9 kDa). It has 5 putative N-glycosylation sites on each polypeptide chain and the attached carbohydrates exhibit some degree of chain heterogeneity, including heterogeneity in terminal sialic acid residues, except at the site associated with the Fc domain, which is unsialylated
Indication/Disease The opthalmic agent is used for the treatment of neovascular (wet) age-related mascular degeneration (AMD) and macular edema following central retinal vein occulsion (CRVO). The systemic injection, known as ziv-aflibercept, in combination with 5-fluorouracil, leucovorin, irinotecan-(FOLFIRI), is for the treatment of metastatic colorectal cancer that is resistant to or progressed following treatment with oxaliplatin.
Pharmacodynamics Compared to other anti-VEGF drugs like bevacizumab and ranibizumab, aflibercept has a higher binding affinity to VEGF-A (Kd = 0.5 pM).
Mechanism of Action Ablibercept is a recombinant fusion protein that acts as a decoy receptor for the ligands, vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PIGF). It prevents these ligands to binding to endothelial receptors, VEGFR-1 and VEGFR-2, to suppress neovascularization and decrease vascular permeability. This ultimately will slow vision loss or the progression of metastatic colorectal cancer.
Toxicity For all intravitreal VEGF inhibitors, there is increased risk of stroke and myocardial infarction. An increase in intraocular pressure may also occur. When used intravenously, most common adverse reactions were leukopenia, diarrhea, neutropenia, proteinuria, AST increased, stomatitis, fatigue, thrombocytopenia, ALT increased, hypertension, weight decreased, decreased appetite, epistaxis, abdominal pain, dysphonia, serum creatinine increased, and headache.
Metabolism Because aflibercept is a protein, it is expected to be broken down via proteolysis into smaller peptides and amino acids. The cytochrome P450 enzyme system is not involved in the metabolism of aflibercept.
Absorption In patients with wet AMD and CRVO, the mean peak plasma concentration (Cmax) was 0.02 mcg/mL and 0.05 mcg/mL respectively. These concentrations were reached in 1 to 3 days. Aflibercept did not accumulate when administered as repeated doses intravitreally every 4 weeks.
Volume of Distribution After Intravenous infusion of aflibercept, the volume of distribution is 6 L.
Clearance When cancer patients were given 2-9 mg/kg every 2 or 3 week; 1 hour IV infusion of aflibercept the typical estimated clearances were as follows:CL of free aflibercept (CLf) = 0.88 L/day;CL of bound aflibercept (CLf) = 0.19 L/day;Patients clear free aflibercept faster if they had low albumin or high alkaline phosphatase levels.
Categories Antineoplastic Agents and Ophthalmics
Patents Number US7608261
Date of Issue 28/10/13
Date of Expiry 15/06/31
Drug Interaction N.A.
Target N.A.
Information of corresponding available drug in the market
Brand Name N.A.
Company N.A.
Brand Discription N.A.
Prescribed for N.A.
Chemical Name N.A.
Formulation N.A.
Physcial Appearance N.A.
Route of Administration N.A.
Recommended Dosage N.A.
Contraindication N.A.
Side Effects N.A.
Useful Link N.A.
PubMed ID 25646034, 25634529, 25632361, 25627086, 23673444, 23560774
3-D Structure Th1133 (View) or (Download)

Primary information
ID 1619
ThPP ID Th1133
Therapeutic Peptide/Protein Name Aflibercept
Sequence SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLI view full sequnce in fasta
Functional Classification Ib
Molecular Weight 115000
Chemical Formula C4318H6788N1164O1304S32
Isoelectric Point N.A.
Hydrophobicity N.A.
Melting Point (℃) N.A.
Half Life Intravitreal half life - 7.13 days
Description Aflibercept is a vascular endothelial growth factor (VEGF) inhibitor. It is a recombinant dimeric fusion glycoprotein that comprises (VEGF) binding portions from the extracellular domains of human VEGF receptors 1 and 2, this is fused to the Fc portion of human IgG1. It contains approximately 15% glycosylation to give a total molecular weight of 115 kDa (protein part = 96.9 kDa). It has 5 putative N-glycosylation sites on each polypeptide chain and the attached carbohydrates exhibit some degree of chain heterogeneity, including heterogeneity in terminal sialic acid residues, except at the site associated with the Fc domain, which is unsialylated
Indication/Disease The opthalmic agent is used for the treatment of neovascular (wet) age-related mascular degeneration (AMD) and macular edema following central retinal vein occulsion (CRVO). The systemic injection, known as ziv-aflibercept, in combination with 5-fluorouracil, leucovorin, irinotecan-(FOLFIRI), is for the treatment of metastatic colorectal cancer that is resistant to or progressed following treatment with oxaliplatin.
Pharmacodynamics Compared to other anti-VEGF drugs like bevacizumab and ranibizumab, aflibercept has a higher binding affinity to VEGF-A (Kd = 0.5 pM).
Mechanism of Action Ablibercept is a recombinant fusion protein that acts as a decoy receptor for the ligands, vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PIGF). It prevents these ligands to binding to endothelial receptors, VEGFR-1 and VEGFR-2, to suppress neovascularization and decrease vascular permeability. This ultimately will slow vision loss or the progression of metastatic colorectal cancer.
Toxicity For all intravitreal VEGF inhibitors, there is increased risk of stroke and myocardial infarction. An increase in intraocular pressure may also occur. When used intravenously, most common adverse reactions were leukopenia, diarrhea, neutropenia, proteinuria, AST increased, stomatitis, fatigue, thrombocytopenia, ALT increased, hypertension, weight decreased, decreased appetite, epistaxis, abdominal pain, dysphonia, serum creatinine increased, and headache.
Metabolism Because aflibercept is a protein, it is expected to be broken down via proteolysis into smaller peptides and amino acids. The cytochrome P450 enzyme system is not involved in the metabolism of aflibercept.
Absorption In patients with wet AMD and CRVO, the mean peak plasma concentration (Cmax) was 0.02 mcg/mL and 0.05 mcg/mL respectively. These concentrations were reached in 1 to 3 days. Aflibercept did not accumulate when administered as repeated doses intravitreally every 4 weeks.
Volume of Distribution After Intravenous infusion of aflibercept, the volume of distribution is 6 L.
Clearance When cancer patients were given 2-9 mg/kg every 2 or 3 week; 1 hour IV infusion of aflibercept the typical estimated clearances were as follows:CL of free aflibercept (CLf) = 0.88 L/day;CL of bound aflibercept (CLf) = 0.19 L/day;Patients clear free aflibercept faster if they had low albumin or high alkaline phosphatase levels.
Categories Antineoplastic Agents and Ophthalmics
Patents Number US7070959
Date of Issue 05/07/10
Date of Expiry 24/05/24
Drug Interaction N.A.
Target N.A.
Information of corresponding available drug in the market
Brand Name N.A.
Company N.A.
Brand Discription N.A.
Prescribed for N.A.
Chemical Name N.A.
Formulation N.A.
Physcial Appearance N.A.
Route of Administration N.A.
Recommended Dosage N.A.
Contraindication N.A.
Side Effects N.A.
Useful Link N.A.
PubMed ID 25646034, 25634529, 25632361, 25627086, 23673444, 23560774
3-D Structure Th1133 (View) or (Download)

Primary information
ID 1620
ThPP ID Th1133
Therapeutic Peptide/Protein Name Aflibercept
Sequence SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLI view full sequnce in fasta
Functional Classification Ib
Molecular Weight 115000
Chemical Formula C4318H6788N1164O1304S32
Isoelectric Point N.A.
Hydrophobicity N.A.
Melting Point (℃) N.A.
Half Life Intravitreal half life - 7.13 days
Description Aflibercept is a vascular endothelial growth factor (VEGF) inhibitor. It is a recombinant dimeric fusion glycoprotein that comprises (VEGF) binding portions from the extracellular domains of human VEGF receptors 1 and 2, this is fused to the Fc portion of human IgG1. It contains approximately 15% glycosylation to give a total molecular weight of 115 kDa (protein part = 96.9 kDa). It has 5 putative N-glycosylation sites on each polypeptide chain and the attached carbohydrates exhibit some degree of chain heterogeneity, including heterogeneity in terminal sialic acid residues, except at the site associated with the Fc domain, which is unsialylated
Indication/Disease The opthalmic agent is used for the treatment of neovascular (wet) age-related mascular degeneration (AMD) and macular edema following central retinal vein occulsion (CRVO). The systemic injection, known as ziv-aflibercept, in combination with 5-fluorouracil, leucovorin, irinotecan-(FOLFIRI), is for the treatment of metastatic colorectal cancer that is resistant to or progressed following treatment with oxaliplatin.
Pharmacodynamics Compared to other anti-VEGF drugs like bevacizumab and ranibizumab, aflibercept has a higher binding affinity to VEGF-A (Kd = 0.5 pM).
Mechanism of Action Ablibercept is a recombinant fusion protein that acts as a decoy receptor for the ligands, vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PIGF). It prevents these ligands to binding to endothelial receptors, VEGFR-1 and VEGFR-2, to suppress neovascularization and decrease vascular permeability. This ultimately will slow vision loss or the progression of metastatic colorectal cancer.
Toxicity For all intravitreal VEGF inhibitors, there is increased risk of stroke and myocardial infarction. An increase in intraocular pressure may also occur. When used intravenously, most common adverse reactions were leukopenia, diarrhea, neutropenia, proteinuria, AST increased, stomatitis, fatigue, thrombocytopenia, ALT increased, hypertension, weight decreased, decreased appetite, epistaxis, abdominal pain, dysphonia, serum creatinine increased, and headache.
Metabolism Because aflibercept is a protein, it is expected to be broken down via proteolysis into smaller peptides and amino acids. The cytochrome P450 enzyme system is not involved in the metabolism of aflibercept.
Absorption In patients with wet AMD and CRVO, the mean peak plasma concentration (Cmax) was 0.02 mcg/mL and 0.05 mcg/mL respectively. These concentrations were reached in 1 to 3 days. Aflibercept did not accumulate when administered as repeated doses intravitreally every 4 weeks.
Volume of Distribution After Intravenous infusion of aflibercept, the volume of distribution is 6 L.
Clearance When cancer patients were given 2-9 mg/kg every 2 or 3 week; 1 hour IV infusion of aflibercept the typical estimated clearances were as follows:CL of free aflibercept (CLf) = 0.88 L/day;CL of bound aflibercept (CLf) = 0.19 L/day;Patients clear free aflibercept faster if they had low albumin or high alkaline phosphatase levels.
Categories Antineoplastic Agents and Ophthalmics
Patents Number US7374757
Date of Issue 21/05/12
Date of Expiry 24/05/24
Drug Interaction N.A.
Target N.A.
Information of corresponding available drug in the market
Brand Name N.A.
Company N.A.
Brand Discription N.A.
Prescribed for N.A.
Chemical Name N.A.
Formulation N.A.
Physcial Appearance N.A.
Route of Administration N.A.
Recommended Dosage N.A.
Contraindication N.A.
Side Effects N.A.
Useful Link N.A.
PubMed ID 25646034, 25634529, 25632361, 25627086, 23673444, 23560774
3-D Structure Th1133 (View) or (Download)

OSDDlinux

Raghava's Group

IMTECH

CSIR

CRDD
CPPSITE 2.0

Primary information
ID	1615
ThPP ID	Th1133
Therapeutic Peptide/Protein Name	Aflibercept
Sequence	SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLI view full sequnce in fasta
Functional Classification	Ib
Molecular Weight	115000
Chemical Formula	C4318H6788N1164O1304S32
Isoelectric Point	N.A.
Hydrophobicity	N.A.
Melting Point (℃)	N.A.
Half Life	Intravitreal half life - 7.13 days
Description	Aflibercept is a vascular endothelial growth factor (VEGF) inhibitor. It is a recombinant dimeric fusion glycoprotein that comprises (VEGF) binding portions from the extracellular domains of human VEGF receptors 1 and 2, this is fused to the Fc portion of human IgG1. It contains approximately 15% glycosylation to give a total molecular weight of 115 kDa (protein part = 96.9 kDa). It has 5 putative N-glycosylation sites on each polypeptide chain and the attached carbohydrates exhibit some degree of chain heterogeneity, including heterogeneity in terminal sialic acid residues, except at the site associated with the Fc domain, which is unsialylated.
Indication/Disease	The opthalmic agent is used for the treatment of neovascular (wet) age-related mascular degeneration (AMD) and macular edema following central retinal vein occulsion (CRVO). The systemic injection, known as ziv-aflibercept, in combination with 5-fluorouracil, leucovorin, irinotecan-(FOLFIRI), is for the treatment of metastatic colorectal cancer that is resistant to or progressed following treatment with oxaliplatin.
Pharmacodynamics	Compared to other anti-VEGF drugs like bevacizumab and ranibizumab, aflibercept has a higher binding affinity to VEGF-A (Kd = 0.5 pM).
Mechanism of Action	Ablibercept is a recombinant fusion protein that acts as a decoy receptor for the ligands, vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PIGF). It prevents these ligands to binding to endothelial receptors, VEGFR-1 and VEGFR-2, to suppress neovascularization and decrease vascular permeability. This ultimately will slow vision loss or the progression of metastatic colorectal cancer.
Toxicity	For all intravitreal VEGF inhibitors, there is increased risk of stroke and myocardial infarction. An increase in intraocular pressure may also occur. When used intravenously, most common adverse reactions were leukopenia, diarrhea, neutropenia, proteinuria, AST increased, stomatitis, fatigue, thrombocytopenia, ALT increased, hypertension, weight decreased, decreased appetite, epistaxis, abdominal pain, dysphonia, serum creatinine increased, and headache.
Metabolism	Because aflibercept is a protein, it is expected to be broken down via proteolysis into smaller peptides and amino acids. The cytochrome P450 enzyme system is not involved in the metabolism of aflibercept.
Absorption	In patients with wet AMD and CRVO, the mean peak plasma concentration (Cmax) was 0.02 mcg/mL and 0.05 mcg/mL respectively. These concentrations were reached in 1 to 3 days. Aflibercept did not accumulate when administered as repeated doses intravitreally every 4 weeks.
Volume of Distribution	After Intravenous infusion of aflibercept, the volume of distribution is 6 L.
Clearance	When cancer patients were given 2-9 mg/kg every 2 or 3 week; 1 hour IV infusion of aflibercept the typical estimated clearances were as follows:CL of free aflibercept (CLf) = 0.88 L/day;CL of bound aflibercept (CLf) = 0.19 L/day;Patients clear free aflibercept faster if they had low albumin or high alkaline phosphatase levels.
Categories	Antineoplastic Agents and Ophthalmics
Patents Number	US7306799
Date of Issue	26/03/09
Date of Expiry	24/05/24
Drug Interaction	N.A.
Target	Vascular endothelial growth factor A,Placenta growth factor,Vascular endothelial growth factor B
Information of corresponding available drug in the market
Brand Name	Eylea
Company	Regeneron Pharmaceuticals
Brand Discription	EYLEA (aflibercept) is a recombinant fusion protein consisting of portions of human VEGF receptors 1 and 2 extracellular domains fused to the Fc portion of human IgG1 formulated as an iso-osmotic solution for intravitreal administration. Aflibercept is a dimeric glycoprotein with a protein molecular weight of 97 kilodaltons (kDa) and contains glycosylation, constituting an additional 15% of the total molecular mass, resulting in a total molecular weight of 115 kDa. Aflibercept is produced in recombinant Chinese hamster ovary (CHO) cells.
Prescribed for	Neovascular (Wet) Age-Related Macular Degeneration (AMD), Macular Edema Following Central Retinal Vein Occlusion (CRVO)
Chemical Name	N.A.
Formulation	EYLEA is supplied as a preservative-free, sterile, aqueous solution in a single-use, glass vial designed to deliver 0.05 mL (50 microliters) of EYLEA (40 mg/mL in 10 mM sodium phosphate, 40 mM sodium chloride, 0.03% polysorbate 20, and 5% sucrose, pH 6.2).
Physcial Appearance	EYLEA is a sterile, clear, and colorless to pale yellow solution.
Route of Administration	Intravitreal Injection
Recommended Dosage	The recommended dose for EYLEA is 2 mg (0.05 mL or 50 microliters) administered by intravitreal injection every 4 weeks (monthly) for the first 12 weeks (3 months), followed by 2 mg (0.05 mL) via intravitreal injection once every 8 weeks (2 months).
Contraindication	ocular or periocular infections, active intraocular inflammation, Hypersensitivity
Side Effects	Endophthalmitis and retinal detachments, Increased intraocular pressure, Thromboembolic events
Useful Link	http://www.rxlist.com/eylea-drug.htm http://www.eylea.com/international/?p=/eylea-home/index.php http://www.drugs.com/eylea.html
PubMed ID	25646034, 25634529, 25632361, 25627086, 23673444, 23560774
3-D Structure	Th1133 (View) or (Download)

Primary information
ID	1616
ThPP ID	Th1133
Therapeutic Peptide/Protein Name	Aflibercept
Sequence	SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLI view full sequnce in fasta
Functional Classification	Ib
Molecular Weight	115000
Chemical Formula	C4318H6788N1164O1304S32
Isoelectric Point	N.A.
Hydrophobicity	N.A.
Melting Point (℃)	N.A.
Half Life	Intravitreal half life - 7.13 days
Description	Aflibercept is a vascular endothelial growth factor (VEGF) inhibitor. It is a recombinant dimeric fusion glycoprotein that comprises (VEGF) binding portions from the extracellular domains of human VEGF receptors 1 and 2, this is fused to the Fc portion of human IgG1. It contains approximately 15% glycosylation to give a total molecular weight of 115 kDa (protein part = 96.9 kDa). It has 5 putative N-glycosylation sites on each polypeptide chain and the attached carbohydrates exhibit some degree of chain heterogeneity, including heterogeneity in terminal sialic acid residues, except at the site associated with the Fc domain, which is unsialylated
Indication/Disease	The opthalmic agent is used for the treatment of neovascular (wet) age-related mascular degeneration (AMD) and macular edema following central retinal vein occulsion (CRVO). The systemic injection, known as ziv-aflibercept, in combination with 5-fluorouracil, leucovorin, irinotecan-(FOLFIRI), is for the treatment of metastatic colorectal cancer that is resistant to or progressed following treatment with oxaliplatin.
Pharmacodynamics	Compared to other anti-VEGF drugs like bevacizumab and ranibizumab, aflibercept has a higher binding affinity to VEGF-A (Kd = 0.5 pM).
Mechanism of Action	Ablibercept is a recombinant fusion protein that acts as a decoy receptor for the ligands, vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PIGF). It prevents these ligands to binding to endothelial receptors, VEGFR-1 and VEGFR-2, to suppress neovascularization and decrease vascular permeability. This ultimately will slow vision loss or the progression of metastatic colorectal cancer.
Toxicity	For all intravitreal VEGF inhibitors, there is increased risk of stroke and myocardial infarction. An increase in intraocular pressure may also occur. When used intravenously, most common adverse reactions were leukopenia, diarrhea, neutropenia, proteinuria, AST increased, stomatitis, fatigue, thrombocytopenia, ALT increased, hypertension, weight decreased, decreased appetite, epistaxis, abdominal pain, dysphonia, serum creatinine increased, and headache.
Metabolism	Because aflibercept is a protein, it is expected to be broken down via proteolysis into smaller peptides and amino acids. The cytochrome P450 enzyme system is not involved in the metabolism of aflibercept.
Absorption	In patients with wet AMD and CRVO, the mean peak plasma concentration (Cmax) was 0.02 mcg/mL and 0.05 mcg/mL respectively. These concentrations were reached in 1 to 3 days. Aflibercept did not accumulate when administered as repeated doses intravitreally every 4 weeks.
Volume of Distribution	After Intravenous infusion of aflibercept, the volume of distribution is 6 L.
Clearance	When cancer patients were given 2-9 mg/kg every 2 or 3 week; 1 hour IV infusion of aflibercept the typical estimated clearances were as follows:CL of free aflibercept (CLf) = 0.88 L/day;CL of bound aflibercept (CLf) = 0.19 L/day;Patients clear free aflibercept faster if they had low albumin or high alkaline phosphatase levels.
Categories	Antineoplastic Agents and Ophthalmics
Patents Number	US7531173
Date of Issue	13/05/13
Date of Expiry	03/02/30
Drug Interaction	N.A.
Target	N.A.
Information of corresponding available drug in the market
Brand Name	Zaltrap
Company	Sanofi and Regeneron Pharmaceuticals, Inc.
Brand Discription	Ziv-aflibercept is a recombinant fusion protein consisting of Vascular Endothelial Growth Factor (VEGF)-binding portions from the extracellular domains of human VEGF Receptors 1 and 2 fused to the Fc portion of the human IgG1. Ziv-aflibercept is produced by recombinant DNA technology in a Chinese hamster ovary (CHO) K-1 mammalian expression system. Ziv-aflibercept is a dimeric glycoprotein with a protein molecular weight of 97 kilodaltons (kDa) and contains glycosylation, constituting an additional 15% of the total molecular mass, resulting in a total molecular weight of 115 kDa.
Prescribed for	metastatic colorectal cancer (mCRC) that is resistant to or has progressed following an oxaliplatin-containing regimen
Chemical Name	N.A.
Formulation	ZALTRAP is supplied in single-use vials of 100 mg per 4 ml and 200 mg per 8 ml formulated as 25 mg/mL ziv-aflibercept in polysorbate 20 (0.1%), sodium chloride (100 mM), sodium citrate (5 mM), sodium phosphate (5 mM), and sucrose (20%), in Water for Injection USP, at a pH of 6.2.
Physcial Appearance	ZALTRAP is a sterile, clear, colorless to pale yellow, non-pyrogenic, preservative-free, solution for administration by Intravenous infusion.
Route of Administration	Intravenous infusion
Recommended Dosage	4 mg per kg as an intravenous (IV) infusion over 1 hour every two weeks.
Contraindication	N.A.
Side Effects	Hemorrhage, Gastrointestinal, Compromised Wound Healing, Fistula Formation, Hypertension, Arterial Thromboembolic Events, Proteinuria, Neutropenia and Neutropenic Complications, Diarrhea and Dehydration, Reversible Posterior Leukoencephalopathy Syndrome
Useful Link	http://www.rxlist.com/zaltrap-drug.htm http://www.zaltrap.com/ http://en.wikipedia.org/wiki/Aflibercept
PubMed ID	25646034, 25634529, 25632361, 25627086, 23673444, 23560774
3-D Structure	Th1133 (View) or (Download)

Primary information
ID	1617
ThPP ID	Th1133
Therapeutic Peptide/Protein Name	Aflibercept
Sequence	SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLI view full sequnce in fasta
Functional Classification	Ib
Molecular Weight	115000
Chemical Formula	C4318H6788N1164O1304S32
Isoelectric Point	N.A.
Hydrophobicity	N.A.
Melting Point (℃)	N.A.
Half Life	Intravitreal half life - 7.13 days
Description	Aflibercept is a vascular endothelial growth factor (VEGF) inhibitor. It is a recombinant dimeric fusion glycoprotein that comprises (VEGF) binding portions from the extracellular domains of human VEGF receptors 1 and 2, this is fused to the Fc portion of human IgG1. It contains approximately 15% glycosylation to give a total molecular weight of 115 kDa (protein part = 96.9 kDa). It has 5 putative N-glycosylation sites on each polypeptide chain and the attached carbohydrates exhibit some degree of chain heterogeneity, including heterogeneity in terminal sialic acid residues, except at the site associated with the Fc domain, which is unsialylated
Indication/Disease	The opthalmic agent is used for the treatment of neovascular (wet) age-related mascular degeneration (AMD) and macular edema following central retinal vein occulsion (CRVO). The systemic injection, known as ziv-aflibercept, in combination with 5-fluorouracil, leucovorin, irinotecan-(FOLFIRI), is for the treatment of metastatic colorectal cancer that is resistant to or progressed following treatment with oxaliplatin.
Pharmacodynamics	Compared to other anti-VEGF drugs like bevacizumab and ranibizumab, aflibercept has a higher binding affinity to VEGF-A (Kd = 0.5 pM).
Mechanism of Action	Ablibercept is a recombinant fusion protein that acts as a decoy receptor for the ligands, vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PIGF). It prevents these ligands to binding to endothelial receptors, VEGFR-1 and VEGFR-2, to suppress neovascularization and decrease vascular permeability. This ultimately will slow vision loss or the progression of metastatic colorectal cancer.
Toxicity	For all intravitreal VEGF inhibitors, there is increased risk of stroke and myocardial infarction. An increase in intraocular pressure may also occur. When used intravenously, most common adverse reactions were leukopenia, diarrhea, neutropenia, proteinuria, AST increased, stomatitis, fatigue, thrombocytopenia, ALT increased, hypertension, weight decreased, decreased appetite, epistaxis, abdominal pain, dysphonia, serum creatinine increased, and headache.
Metabolism	Because aflibercept is a protein, it is expected to be broken down via proteolysis into smaller peptides and amino acids. The cytochrome P450 enzyme system is not involved in the metabolism of aflibercept.
Absorption	In patients with wet AMD and CRVO, the mean peak plasma concentration (Cmax) was 0.02 mcg/mL and 0.05 mcg/mL respectively. These concentrations were reached in 1 to 3 days. Aflibercept did not accumulate when administered as repeated doses intravitreally every 4 weeks.
Volume of Distribution	After Intravenous infusion of aflibercept, the volume of distribution is 6 L.
Clearance	When cancer patients were given 2-9 mg/kg every 2 or 3 week; 1 hour IV infusion of aflibercept the typical estimated clearances were as follows:CL of free aflibercept (CLf) = 0.88 L/day;CL of bound aflibercept (CLf) = 0.19 L/day;Patients clear free aflibercept faster if they had low albumin or high alkaline phosphatase levels.
Categories	Antineoplastic Agents and Ophthalmics
Patents Number	US7374758
Date of Issue	21/05/12
Date of Expiry	24/05/24
Drug Interaction	N.A.
Target	N.A.
Information of corresponding available drug in the market
Brand Name	N.A.
Company	N.A.
Brand Discription	N.A.
Prescribed for	N.A.
Chemical Name	N.A.
Formulation	N.A.
Physcial Appearance	N.A.
Route of Administration	N.A.
Recommended Dosage	N.A.
Contraindication	N.A.
Side Effects	N.A.
Useful Link	N.A.
PubMed ID	25646034, 25634529, 25632361, 25627086, 23673444, 23560774
3-D Structure	Th1133 (View) or (Download)

Primary information
ID	1618
ThPP ID	Th1133
Therapeutic Peptide/Protein Name	Aflibercept
Sequence	SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLI view full sequnce in fasta
Functional Classification	Ib
Molecular Weight	115000
Chemical Formula	C4318H6788N1164O1304S32
Isoelectric Point	N.A.
Hydrophobicity	N.A.
Melting Point (℃)	N.A.
Half Life	Intravitreal half life - 7.13 days
Description	Aflibercept is a vascular endothelial growth factor (VEGF) inhibitor. It is a recombinant dimeric fusion glycoprotein that comprises (VEGF) binding portions from the extracellular domains of human VEGF receptors 1 and 2, this is fused to the Fc portion of human IgG1. It contains approximately 15% glycosylation to give a total molecular weight of 115 kDa (protein part = 96.9 kDa). It has 5 putative N-glycosylation sites on each polypeptide chain and the attached carbohydrates exhibit some degree of chain heterogeneity, including heterogeneity in terminal sialic acid residues, except at the site associated with the Fc domain, which is unsialylated
Indication/Disease	The opthalmic agent is used for the treatment of neovascular (wet) age-related mascular degeneration (AMD) and macular edema following central retinal vein occulsion (CRVO). The systemic injection, known as ziv-aflibercept, in combination with 5-fluorouracil, leucovorin, irinotecan-(FOLFIRI), is for the treatment of metastatic colorectal cancer that is resistant to or progressed following treatment with oxaliplatin.
Pharmacodynamics	Compared to other anti-VEGF drugs like bevacizumab and ranibizumab, aflibercept has a higher binding affinity to VEGF-A (Kd = 0.5 pM).
Mechanism of Action	Ablibercept is a recombinant fusion protein that acts as a decoy receptor for the ligands, vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PIGF). It prevents these ligands to binding to endothelial receptors, VEGFR-1 and VEGFR-2, to suppress neovascularization and decrease vascular permeability. This ultimately will slow vision loss or the progression of metastatic colorectal cancer.
Toxicity	For all intravitreal VEGF inhibitors, there is increased risk of stroke and myocardial infarction. An increase in intraocular pressure may also occur. When used intravenously, most common adverse reactions were leukopenia, diarrhea, neutropenia, proteinuria, AST increased, stomatitis, fatigue, thrombocytopenia, ALT increased, hypertension, weight decreased, decreased appetite, epistaxis, abdominal pain, dysphonia, serum creatinine increased, and headache.
Metabolism	Because aflibercept is a protein, it is expected to be broken down via proteolysis into smaller peptides and amino acids. The cytochrome P450 enzyme system is not involved in the metabolism of aflibercept.
Absorption	In patients with wet AMD and CRVO, the mean peak plasma concentration (Cmax) was 0.02 mcg/mL and 0.05 mcg/mL respectively. These concentrations were reached in 1 to 3 days. Aflibercept did not accumulate when administered as repeated doses intravitreally every 4 weeks.
Volume of Distribution	After Intravenous infusion of aflibercept, the volume of distribution is 6 L.
Clearance	When cancer patients were given 2-9 mg/kg every 2 or 3 week; 1 hour IV infusion of aflibercept the typical estimated clearances were as follows:CL of free aflibercept (CLf) = 0.88 L/day;CL of bound aflibercept (CLf) = 0.19 L/day;Patients clear free aflibercept faster if they had low albumin or high alkaline phosphatase levels.
Categories	Antineoplastic Agents and Ophthalmics
Patents Number	US7608261
Date of Issue	28/10/13
Date of Expiry	15/06/31
Drug Interaction	N.A.
Target	N.A.
Information of corresponding available drug in the market
Brand Name	N.A.
Company	N.A.
Brand Discription	N.A.
Prescribed for	N.A.
Chemical Name	N.A.
Formulation	N.A.
Physcial Appearance	N.A.
Route of Administration	N.A.
Recommended Dosage	N.A.
Contraindication	N.A.
Side Effects	N.A.
Useful Link	N.A.
PubMed ID	25646034, 25634529, 25632361, 25627086, 23673444, 23560774
3-D Structure	Th1133 (View) or (Download)

Primary information
ID	1619
ThPP ID	Th1133
Therapeutic Peptide/Protein Name	Aflibercept
Sequence	SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLI view full sequnce in fasta
Functional Classification	Ib
Molecular Weight	115000
Chemical Formula	C4318H6788N1164O1304S32
Isoelectric Point	N.A.
Hydrophobicity	N.A.
Melting Point (℃)	N.A.
Half Life	Intravitreal half life - 7.13 days
Description	Aflibercept is a vascular endothelial growth factor (VEGF) inhibitor. It is a recombinant dimeric fusion glycoprotein that comprises (VEGF) binding portions from the extracellular domains of human VEGF receptors 1 and 2, this is fused to the Fc portion of human IgG1. It contains approximately 15% glycosylation to give a total molecular weight of 115 kDa (protein part = 96.9 kDa). It has 5 putative N-glycosylation sites on each polypeptide chain and the attached carbohydrates exhibit some degree of chain heterogeneity, including heterogeneity in terminal sialic acid residues, except at the site associated with the Fc domain, which is unsialylated
Indication/Disease	The opthalmic agent is used for the treatment of neovascular (wet) age-related mascular degeneration (AMD) and macular edema following central retinal vein occulsion (CRVO). The systemic injection, known as ziv-aflibercept, in combination with 5-fluorouracil, leucovorin, irinotecan-(FOLFIRI), is for the treatment of metastatic colorectal cancer that is resistant to or progressed following treatment with oxaliplatin.
Pharmacodynamics	Compared to other anti-VEGF drugs like bevacizumab and ranibizumab, aflibercept has a higher binding affinity to VEGF-A (Kd = 0.5 pM).
Mechanism of Action	Ablibercept is a recombinant fusion protein that acts as a decoy receptor for the ligands, vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PIGF). It prevents these ligands to binding to endothelial receptors, VEGFR-1 and VEGFR-2, to suppress neovascularization and decrease vascular permeability. This ultimately will slow vision loss or the progression of metastatic colorectal cancer.
Toxicity	For all intravitreal VEGF inhibitors, there is increased risk of stroke and myocardial infarction. An increase in intraocular pressure may also occur. When used intravenously, most common adverse reactions were leukopenia, diarrhea, neutropenia, proteinuria, AST increased, stomatitis, fatigue, thrombocytopenia, ALT increased, hypertension, weight decreased, decreased appetite, epistaxis, abdominal pain, dysphonia, serum creatinine increased, and headache.
Metabolism	Because aflibercept is a protein, it is expected to be broken down via proteolysis into smaller peptides and amino acids. The cytochrome P450 enzyme system is not involved in the metabolism of aflibercept.
Absorption	In patients with wet AMD and CRVO, the mean peak plasma concentration (Cmax) was 0.02 mcg/mL and 0.05 mcg/mL respectively. These concentrations were reached in 1 to 3 days. Aflibercept did not accumulate when administered as repeated doses intravitreally every 4 weeks.
Volume of Distribution	After Intravenous infusion of aflibercept, the volume of distribution is 6 L.
Clearance	When cancer patients were given 2-9 mg/kg every 2 or 3 week; 1 hour IV infusion of aflibercept the typical estimated clearances were as follows:CL of free aflibercept (CLf) = 0.88 L/day;CL of bound aflibercept (CLf) = 0.19 L/day;Patients clear free aflibercept faster if they had low albumin or high alkaline phosphatase levels.
Categories	Antineoplastic Agents and Ophthalmics
Patents Number	US7070959
Date of Issue	05/07/10
Date of Expiry	24/05/24
Drug Interaction	N.A.
Target	N.A.
Information of corresponding available drug in the market
Brand Name	N.A.
Company	N.A.
Brand Discription	N.A.
Prescribed for	N.A.
Chemical Name	N.A.
Formulation	N.A.
Physcial Appearance	N.A.
Route of Administration	N.A.
Recommended Dosage	N.A.
Contraindication	N.A.
Side Effects	N.A.
Useful Link	N.A.
PubMed ID	25646034, 25634529, 25632361, 25627086, 23673444, 23560774
3-D Structure	Th1133 (View) or (Download)

Primary information
ID	1620
ThPP ID	Th1133
Therapeutic Peptide/Protein Name	Aflibercept
Sequence	SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLI view full sequnce in fasta
Functional Classification	Ib
Molecular Weight	115000
Chemical Formula	C4318H6788N1164O1304S32
Isoelectric Point	N.A.
Hydrophobicity	N.A.
Melting Point (℃)	N.A.
Half Life	Intravitreal half life - 7.13 days
Description	Aflibercept is a vascular endothelial growth factor (VEGF) inhibitor. It is a recombinant dimeric fusion glycoprotein that comprises (VEGF) binding portions from the extracellular domains of human VEGF receptors 1 and 2, this is fused to the Fc portion of human IgG1. It contains approximately 15% glycosylation to give a total molecular weight of 115 kDa (protein part = 96.9 kDa). It has 5 putative N-glycosylation sites on each polypeptide chain and the attached carbohydrates exhibit some degree of chain heterogeneity, including heterogeneity in terminal sialic acid residues, except at the site associated with the Fc domain, which is unsialylated
Indication/Disease	The opthalmic agent is used for the treatment of neovascular (wet) age-related mascular degeneration (AMD) and macular edema following central retinal vein occulsion (CRVO). The systemic injection, known as ziv-aflibercept, in combination with 5-fluorouracil, leucovorin, irinotecan-(FOLFIRI), is for the treatment of metastatic colorectal cancer that is resistant to or progressed following treatment with oxaliplatin.
Pharmacodynamics	Compared to other anti-VEGF drugs like bevacizumab and ranibizumab, aflibercept has a higher binding affinity to VEGF-A (Kd = 0.5 pM).
Mechanism of Action	Ablibercept is a recombinant fusion protein that acts as a decoy receptor for the ligands, vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PIGF). It prevents these ligands to binding to endothelial receptors, VEGFR-1 and VEGFR-2, to suppress neovascularization and decrease vascular permeability. This ultimately will slow vision loss or the progression of metastatic colorectal cancer.
Toxicity	For all intravitreal VEGF inhibitors, there is increased risk of stroke and myocardial infarction. An increase in intraocular pressure may also occur. When used intravenously, most common adverse reactions were leukopenia, diarrhea, neutropenia, proteinuria, AST increased, stomatitis, fatigue, thrombocytopenia, ALT increased, hypertension, weight decreased, decreased appetite, epistaxis, abdominal pain, dysphonia, serum creatinine increased, and headache.
Metabolism	Because aflibercept is a protein, it is expected to be broken down via proteolysis into smaller peptides and amino acids. The cytochrome P450 enzyme system is not involved in the metabolism of aflibercept.
Absorption	In patients with wet AMD and CRVO, the mean peak plasma concentration (Cmax) was 0.02 mcg/mL and 0.05 mcg/mL respectively. These concentrations were reached in 1 to 3 days. Aflibercept did not accumulate when administered as repeated doses intravitreally every 4 weeks.
Volume of Distribution	After Intravenous infusion of aflibercept, the volume of distribution is 6 L.
Clearance	When cancer patients were given 2-9 mg/kg every 2 or 3 week; 1 hour IV infusion of aflibercept the typical estimated clearances were as follows:CL of free aflibercept (CLf) = 0.88 L/day;CL of bound aflibercept (CLf) = 0.19 L/day;Patients clear free aflibercept faster if they had low albumin or high alkaline phosphatase levels.
Categories	Antineoplastic Agents and Ophthalmics
Patents Number	US7374757
Date of Issue	21/05/12
Date of Expiry	24/05/24
Drug Interaction	N.A.
Target	N.A.
Information of corresponding available drug in the market
Brand Name	N.A.
Company	N.A.
Brand Discription	N.A.
Prescribed for	N.A.
Chemical Name	N.A.
Formulation	N.A.
Physcial Appearance	N.A.
Route of Administration	N.A.
Recommended Dosage	N.A.
Contraindication	N.A.
Side Effects	N.A.
Useful Link	N.A.
PubMed ID	25646034, 25634529, 25632361, 25627086, 23673444, 23560774
3-D Structure	Th1133 (View) or (Download)

Updated version of this database is available at ThpDB2

Detailed description page of THPdb