DB00928AcitidineDNMT inhibitornucleoside analogDNMT1FDA approved use for treatment of myelodysplastic syndrome (MDS)FDA approvedIt incorporates into RNA and traps DNMT1 enzyme resulting in loss of DNA methylatiion in nascent strand NAMGC8DNMT inhibitor Antisense oligodeoxynucleotidesDNMT1MGC8 in combination with interferon alpha-2beta for treatment of metatstatic renal carcinoma(RCC). Clinical trials for treatment of MDS and acute myeloid leukemia (AML)Phase I trial for MDS and AMLIt is directed to bind to 3' untranslated region of DNMT1 and induces demethylation of DNA and reexpression of hypermethylated genes as p16. NA1-BET 151BET protein inhibitor Dimethylisoxazole templateBET family proteinsPreclinical studies showed anticancer activity in multiple AMLClinical trials for AMLNA 529122221-BET 762BET protein inhibitor 1,4-Benzodiazepine skeleton basedBET family proteinsPreclinical studies showed inhibition of myeloma progression.Clinical trials for myelomaNA 730873-DeazaneplanocinHMT inhibitorNAHMT (Selective inhibitor of EZH2 enzyme)NANANA 76285486A-366HMT inhibitorNAHMT (selective inhibitor of G9a)NANANA 167551Anacardic acidHATS inhibitor (p300(KAT3B) and pCAF (KAT2B) inhibitorsnatural compoundHATS (p300 , IC50 7 uM and pCAF, IC50-5uM)NANANA 25150857BIX-01294HMT inhibitorHMT (selective inhibitor of G9a mediated H3K9me2)selective inhibitor of G9a-mediated H3K9me2 (IC50 OF 1.7)NAIts inhibitory effect is due to protein protein interaction alteration by occupying histone binding pocket of HMTs rathe rthan competition with SAM 1285941C646HAT inhibitor (p300)pyrazoloneHATSNANAIt is competitive p300 inhibitor versus acetyl CoA thus it binds to p300 in the active sites thus excluding acetyl-CoA. 3246390CambinolSirtuin inhibitor (SIRT1, SIRT2 inhibitor)Hydroxynapthaldehyde derivativesSirtuinsCambinol was reported to inhibit tumor growth in Burkitts's lymphoma xenograft models by inducing apoptosis through acetylation of p53 and BCL6NAThe C pocket of sirtuin is the proposed binding site for cambinol 161591ChaetocinHMT inhibitorepidithiodiketopiperazine (natural product)SU (VAR)3-9 CLASS OF KMTsIn vitro studies showed anticancer activities in case of primary myeloma and human tumor cell lines.NANA 969516Curcumin HAT inhibitor (p300)natural compoundHATSIt used as either alone or in combination with other agents is effective against colorectal, pancreatic, breast, prostrate cancer as well as multiple myeloma and head and neck carcinoma.35 clinical trials at various phases are going with curcumin in form of nanoparticles, capsules and solutions.NA DB01262DecitabineDNMT inhibitornucleoside analogDNMT1FDA approved use for treatment of myelodysplastic syndrome (MDS)FDA approvedIt incorporates into DNA and traps DNMT1 enzyme resulting in loss of DNA methylatiion in nascent strand 99681Dihydro-5-azacytidine (DHAC)DNMT inhibitornucleoside analogDNMT1NANANA 72199293EI1HMT inhibitornon-SAM derived catalytic inhibitorsNANANA DB03823Epigallocatechin-3-gallateDNMT inhibitornon nucleoside inhibitorDNMT1It shows cytotoxic effecct in human cancer cell linesNAIt inhibits DNMT1 activity in human cancer cell lines by binding and blocking DNMT1 57345410EPZ-5676HMT inhibitornucleoside analogueHMT (DOT1L)It inhibits DOT1L mediated H3K79 methylation and suppresses leukemogenic genes. Its in clinical trials for heamtological cancers including acute leukemia with rearrangement of MLL gene.Phase 1 clinical trials for haematological malignancies including acute leukemia with rearrangement of MLLNA 66558664EPZ6438 (E7438)HMT inhibitornon-SAM derived catalytic inhibitors (Pyridone derivatives )HMT (Selective inhibitor of EZH2 enzyme)Clinical trials for targeting EZH2 in lymphoma as well as solid tumors with increased HK27me3 levelsclinical trials targeting EZH2 in lymphoma as well as solid tumors with increased levels of H3K27me3NA NAEtinostatHDAC inhibitor benzamide derivativeHDAC 1, 2, 3, 9 (Class I and II)Clinical trials for hematological cancers and solid tumorsClinical trials alone or in combination with other antitumor agents for treatment of hematologoical cancers such as leukemia and melanoma as well as solid tumors including colorectal cancers It either chelates Zn ion of catalytic site of enzyme or binds key amino acid present in the active site 47751FazarabineDNMT inhibitornucleoside analogNANANANA 5281560GarcinolHATS inhibitor (p300(KAT3B) and pCAF (KAT2B) inhibitorspolyisoprenylated benzophenoneHATSIt inhibits DSB repair and enhances senescence in radiosensitized A549 lung and HeLa cervical carcinoma cells. It even blocks proliferation of MCF-7 breast cancer cells in vitro.NANA 5275521GGA (Geranylgeranoic acid)HDM inhibitorHDM (LSD1)In vitro studies showed anticancer properties. It leads to differentiation of neuroblastoma cells through upregulation of H3K4me2NANA 56963315GSK-J1HDM inhibitorHDM (JmjC demthylase inhibitor)It shows reduction in cancer cell proliferation in vitro and in human xenograft modelsNAIt acts by competitively binding 2-oxogluturate repositioning the metal cofactor of the active site inhibiting demethylase reaction. DB01275HydralazineDNMT inhibitornon nucleoside inhibitorNAUsed in combination with standard chemotherapuetics in patients with advanced solid tumorsPhase II trialsIt inhibits DNA methylationby directly binding to catalytic site of DNMT1 NAIsothiazoloneHATS inhibitor (p300(KAT3B) and pCAF (KAT2B) inhibitorsNAHATSInhibits strongly cell proliferation in human colon and ovarian cancerNANA NAJQ1 (thieno-triazolo-1,4-diazepine)BET protein inhibitor Diazepine skeleton basedBET family proteinsAnticancer activity shown in xenograft models of NUT midline carcinoma, and leukemic activity shown in vitro and in vivo studiesNANA 45029394Lys-CoAHATS inhibitor (p300(KAT3B) and pCAF (KAT2B) inhibitorsBisubstrate analoguesHATSNANANA 9865515MocetinostatHDAC inhibitor benzamide derivativeHDAC 1, 2 (Class I and II)It induces apoptosis in maliganat cells and detabilises microtubule formation in mitosis enhancing its cancer cytotoxicity. It was shown to inhibit autopahgy in chronic lymphocytic leukemia (CLL)Phase 1 and Phase2 trials for hematological malignancies and solid tumorsNA DB02701Nicotinamide and NAD analogues Sirtuin inhibitorNicotinamideSirtuinsNicotinamide mediated inhibition of SIRT1 showed anticancer activity in B-cell CLL and in prostrate cancerNA NAD inhibits SIRT activity by binding to enzyme pocket and NAD-analogues compete with NAD+ for NAD+ binding domain inhibiting enzyme activity NANU9056 (1,2-bis (isothiazol-5yl) disulfane)HATS inhibitor (KAT5 (Tip60) inhibitorNAHATSInhibits cell prolifeartion and induces apoptosis via caspase 3 and caspase 9 in different prostrate cancer cell linesNAIt inhibits cell proliferation and even induces apoptosis in cancer cell lines. NAORY-1001HDM inhibitortranylcypromine-based inhibitorHDM (LSD1)It was shown to induce reduction of tumor growth in vivo and in vitroReady to enter in Phase1 clinical trials for MLL treatmentNA 6918837PanobinostatHDAC inhibitor hydroxamic acidHDACS (Class I and II)Clinical trials for treatment of CTCL, non-Hodgkin's and Hodgkin's lymphoma.Phase I trials for treatment of CTCL and refractory Hodgkin's or non-Hodgkin's lymphoma.The hydroxamic group of molecule binds to Zn ion of cataltyic site. DB05103PivanexHDAC inhibitorshort chain fatty acid analogueHDACS (Class I and II)Clinical trials for treatment of leukemia and lymphomaNAIt acts by destroying the catalytic activity of HDAC enzymes by interacting with Zn+2and hydrophobic pocket of enzymes. NAPolyamine conjugatesHATS inhibitorsynthetic derivatives of acetyl CoAHATSNANANA DB00721ProcaineDNMT inhibitornon nucleoside inhibitor (derivative of 4-amino benzoic acid)DNMT1Used in combination with valproic acid for treatment of advanced solid tumorsPhase I trial It inhibits DNA methylationby directly binding to catalytic site of DNMT1 6400741Psammaplin ADNMT and HDAC inhibitornon nucleoside inhibitorDNMTas well HDACsIt shows strong cytotoxic effect in different human tumor cells lines and A549 lung xenograft modelsNA It inhibits both DNMT1 and HDACs DB02709ResveratrolSirtuin activator (SIRT1 activator)polyphenolSirtuinsIt shows anticancer properties by use of xenograft modelsNAIt prevents cancer through the activation of SIRT1 and the consequent downregulation of proteins associated with cancer progression. 702558RG108DNMT inhibitornon nucleoside inhibitor (derivative of propionic acid)DNMT1In vitro studies exhibit its anticancer activity against human prostate cancerNANA 5352062RomidepsinHDAC inhibitor cyclic peptideHDAC 1, 2, 4, 6 (Class I and II)FDA approved use for treatment of CTCL and in clinical trials for treatment of solid tumor in combination with chemotherapeutic drugsFDA approved for treatment of CTCLIt is prodrug which gets converted in cell environment into a form which interacts with Zn ion of catalytic pocket of HDACs. DB01752SAH (S-adenosyl-L-homocysteine)HMT inhibitoranalogue of SAM (S-adenosyl methionine)NANANA 5113032SelisistatSirtuin inhibitor (SIRT1, SIRT2, SIRT3 inhibitor)IndoleSirtuinsCombination treatment with EX-527 and HDACi was found to induce apoptosis in AML cells.NANA 65482SinefunginHMT inhibitorstructural analogue of SAM and SAHHMTs It demonstrates limited effect against HMTs.NANA 5222465Sodium butyrateHDAC inhibitorshort chain fatty acidHDACS (Class I and II)Induced colon cancer growth arrest and inhibition of prostrate , endometrial and cervical carcinomasFailed clinical trials It acts by destroying the catalytic activity of HDAC enzymes by interacting with Zn+2and hydrophobic pocket of enzymes. NASRT1460Sirtuin activator (SIRT1 activator)NASirtuinsNANA It is unrelated to resveratol but activates SIRT1 1000 fold more than resveratol DB04786SuraminSirtuin inhibitor (SIRT1, SIRT2 inhibitor)SuraminSirtuinsAntitumor effects of suramin in combination with cytotoxic agents were observed in xenograft models of prostrate lung and breast cancer cells.Clinical trials for treatment of various cancer typesIt inhibits SIRT activity by binding to active sites of enzyme DB00752tranylcypromine HDM inhibitorNAInhibit colony formation of human mixed lineage leukemia (MLL) AF9 cells.Clinical trials It inhibits LSD by forming adducts with FAD cofactor in the AOL domain 444732Trichostatin AHDAC inhibitorhydroxamic acidHDACS (Class I and II)Is used in combination with cisplastin to obtain strong antitumor efficacy.It induces cell cycle arrest and death by increasing p21 transcription and reducing cyclinB1, Plk1 and survivins. TSA induces upregulation of tumor suppressor miRNAs and downregulation of oncomirs reducing clonogenicity of cancer cells NA It inhibits HDAC by using its phenyl group to pack inhibitor at the active site pocket while hydroxamic acid interacts and chelates zinc ion. 44251522UNC0224HMT inhibitorderivatives of chaetocin HMT(G9a and SET7 and SET9)Inhibits G9a-like protein (GLP) with an IC50 of 15nm and high selectivity against SET7/9 and SET8NANA 46224516UNC0638HMT inhibitorderivatives of chaetocinHMT(G9a and GLP)Inhibits G9a-like protein with IC-50 of 15nm and GLP with IC50 19nmNANA NAUNCO631HMT inhibitorderivatives of chaetocin NANANANA DB00313ValproateHDAC inhibitorshort chain fatty acidHDACS (Class I and II)In AML patients arrests cell proliferation, increased apoptosis and differentiation. It has been used in combination with ATRA for AML treatmentClinical trials for treatment of leukemiaNA DB02546Vorinostat (SAHA)HDAC Inhibitorhydroxamic acidHDACS (Class I and II)FDA approved for treatment of cutaneous T cell lymphoma. Clinical trials for treatment of hematological cancers.FDA approved (first epi-drug) for treatment of CTCLThe hydroxamic group of molecule binds to Zn ion of cataltyic site. 7302y-butyrolactoneHATS inhibitor (Gcn5 (KAT2A) inhibitorNAHATSNANANA DB03068ZebularineDNMT inhibitornucleoside analogDNMT1Preclinical studies for treament of breast cancer and heaptocellular carcinomaNAIt incorporates into DNA and traps DNMT1 enzyme resulting in loss of DNA methylatiion in nascent strand and reactivation of silenced genes.