Lead Optimization
Lead identification/optimization is the one of the most important steps in drug development. The chemical structure of the
lead compound is used as a starting point for chemical modifications in order to improve potency, selectivity, or
pharmacokinetic parameters. Once a molecule is identified, the next step is to check its ADMET (Adsorption, Distribution,
Metabolism, Excretion and Toxicity) properties. If the molecule has no toxicity and no mutagenicity either, it has potential
for use as lead molecule. Further optimization gives better quality of lead molecules. These may subsequently be developed as
drug(s)
Links to databases of drug molecules and small chemical molecules are given below:
Web Servers/Databases/Mirror Sites Link:
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| Drug Molecules Database |
Description |
|
CMC (Comprehensive Medicinal Chemistry)
MDL | database provides 3D models and important biochemical properties including drug class, logP, and pKa values
for over 8,400 pharmaceutical compounds |
|
Dictionary of Drug | structured database holding information on chemical
substances |
|
DrugBank | combines detailed drug (i.e. chemical, pharmacological and
pharmaceutical) data with comprehensive drug target (i.e. sequence, structure, and pathway) information. |
|
Drug@FDA | Information about FDA approved drug
products |
|
MDDR (MDL Drug Data Report) | database
covering the patent literature, journals, meetings and congresses |
|
FDA Drug | list of drugs approved by the
FDA |
|
MedChem | database contains more than 55,000 compounds with
75,000 names and 32,000 CAS numbers. In addition, there are 61,000 measured logP values, 13,900 pKa values, 26,000
activities, and Rubicon 3D coordinates for almost 49,000 structures. |
|
WDI (World Drug Index) | drug database of almost 80,000 drugs
and pharmacologically active compounds, including all marketed drugs |
|
NCI Drug Dictionary | contains technical definitions and synonyms
for drugs/agents used to treat patients with cancer or conditions related to cancer |
|
PharmaGKB | Integrated resource about how variation in human genetics leads to
variation in response to drugs. |
|
Rx List | The internet drug list |
|
SDD (Super Drug Database) | contains 2.396 compounds with 108.198
conformers |
Virtual Screening
| Chemical Compounds Database |
Description |
|
ACD (Available Chemicals Directory)
| chemical sourcing database |
| ASINEX | lead generation and lead optimization |
| Bionet Database | Screening compounds
database |
| CAP (Chemicals
Available for Purchase) | database provides the contents of many commercial suppliers' catalogs from a single
database that is easy to use, consistently formatted, and frequently updated. |
| ChEBi | reely available dictionary of molecular entities focused on
'small' chemical compounds. |
| ChemBank | freely available data derived from small molecules
and small-molecule screens, and resources for studying the data so that biological and medical insights can be
gained. |
| ChemDB | Chemical dataset |
| ChemStar | provides Synthetic Organic Compounds for HTS,
Building Blocks for Combinatorial Chemistry, Custom Synthesis, Pre-plated Library, Virtual Database |
| CSD (Cambridge Structural Database) | world repository of small
molecule crystal structures |
| HIC-Up (Hetero-compound Information Centre - Uppsala) | freely
accessible resource for structural biologists who are dealing dealing with hetero-compounds ("small molecules") |
| IBS (Inter Biosceen) Database | Chemical library for screening |
| Maybridge Database | designs and produces innovative chemical Building
Blocks and Screening Compounds, and provides Medicinal Chemistry for the drug discovery industry |
| MDPI (Molecular Diversity Preservation International) | Compounds
Database |
| MSDchem | Consistent and enriched library of
ligands, small molecules and monomers that are referred as residues and hetgroups in any PDB entry |
| NCI Database | |
| PDBsum | provides an at-a-glance overview of every macromolecular structure deposited in the
Protein Data Bank (PDB), giving schematic diagrams of the molecules in each structure and of the interactions between
them. |
| PubChem | provides information on the biological activities of
small molecules |
| Relibase | ligand
overlays and binding mode comparisons |
| SPRESI | database containing over 6.1 million molecules, 3.85 million
reactions, 636,000 references, 164,000 patents |
| Zinc | contains over 8 million purchasable compounds in ready-
to-dock, 3D formats |
| Virtual Screening |
Description |
| ChemDB | Chemical dataset |
| ChemID Plus | allows users to search compound identifiers
such as chemical name or CAS Registry Number on the NLM ChemIDplus database of over 370,000 chemicals. |
| ChemBank | allows users to search small
compounds, assays and proteins |
| ZINC | contains over 8 million purchasable compounds in ready-
to-dock, 3D formats |
| IB Screen database | Chemical library for screening |
| Maybridge Database | designs and produces innovative
chemical Building Blocks and Screening Compounds, and provides Medicinal Chemistry for the drug discovery industry |
| MDL SCD | Consolidated
Supplier Catalogs for High-Throughput Screening |
| Bioscreening | Online searchable database of available
compounds |
| TimTec | synthetic organic compound
library |
| RPBS ADME
Tox | ADME-Tox (poor absorption, distribution, metabolism, elimination (ADME) or toxicity) filtering for small
compounds |
| PDB Chemical Search | Substructure search against
8458 chemical compounds from PDB |
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| Other Databases |
Description |
|
ADME DB | database containing information on Human Cytochrome P450
metabolism, kinetics, transporter and structure |
| DTP AIDS Antiviral Screen | AIDS antiviral
screeninf library |
| GLIDA:GPCR Ligand Database | A
complex information system covering biological information of GPCRs as well as chemical information of their known
ligands. |
| NCI Anti Cancer Agent | DTP Human
Tumor Cell Line Screen |
| Pharmeks | diverse, predominantly heterocyclic, organic
library |
| RPSB Collection | databases of
small chemical compounds to identify potential hits that could block the active site or exosite of a target protein |
| Anti HIV/OI Chemical Compounds
Database | Anti-HIV/OI chemical compound database |
| FDA Databases | different FDA drug and drug related
information databases |
| Pesticide Database | Pesticide
database |
| Ligand Binding Affinities |
Description |
AffinDB | Affinity database for protein-ligand |
| BindingDB | web-accessible database of experimentally
determined protein<96>ligand binding affinities |
| DLRP | database of protein ligand and protein receptor
pairs that are known to interact with each other |
| DrugBank | detailed drug (i.e. chemical, pharmacological and
pharmaceutical) data with comprehensive drug target (i.e. sequence, structure, and pathway) information |
| Ligand dissociation constants for GPCRs | provide
information on ligand dissociation constants for GPCRs |
| KiBank | database contains binding
affinity, structures of chemicals and target proteins, and many useful links and information. |
| PDBbind | collection of experimentally measured binding affinity
data |
| PDSP Drug KiDB | provides screening of novel
psychoactive compounds for pharmacological and functional activity at cloned human or rodent CNS receptors, channels, and
transporters |
| Relibase | easy searching
of protein-ligand complexes |
| SCORPIO(structure-calorimetry) | FREE online
|
| WOMBAT | WOrld of Molecular
BioAcTivity |
Standalone Softwares
| Software for Screening |
Description |
|
|
| Calalyst (Discovery studio) | collection of
pharmacophore modeling tools |
| Sybyl | Computational Informatics Software for Molecular
Modelers |
| Vlife Sciences | collection of various applications
related to drug and molecular discovery |
| Schrordinger | chemical simulation
software |
| Software for Molecular Descriptor
Calculation |
Description |
|
|
| ADAPT | a computational model platform developed
for pharmacokinetic and pharmacodynamic applications |
| Dragon | an application for the calculation
of molecular descriptors |
| MolconZ | standard program for generation of Molecular
Connectivity, Shape, and Information Indices for Quantitative Structure Activity Relationship (QSAR) Analyses |
| MOE | integrates tools for computer-assisted drug discovery |
| OpenMolGrid | drug-design using Grid technology |
| VLife MDS | workbench for computer aided drug
design (CADD) and molecule discovery |
| Codessa | advanced, fully featured Quantitative
Structure/Activity Relationship (QSAR) program that ties information from AMPAC<99> and other Quantum Mechanics programs with
experimental data |
| JoeLib | Cheminformatics algorithm library, which was designed for
prototyping, data mining, graph mining, and of course algorithm development |
| CDK | Open source Java computational chemistry package which supports
chemical structure drawing and the graphical layout of 2D chemical structures. |
| PreADMET | Descriptor Calculation, Druglikeness
Prediction: Rule-based Druglike Screening, ADME Prediction: Examination of various ADME properties of drug candidates,
Chemical Library Design: Powerful Workspace, Molecular Set and Molecular Table |
| ADMETWorks ModelBuilder | a tool for
building mathematical models that can later be used for predicting various chemical and biological properties of
compounds |
| CAChe | computer-aided chemistry modelling package designed for
experimental chemists conducting research in life science, materials and chemistry |
| VolSurf | a computational procedure
aimed to produce and to explore the physicochemical property space of a molecule (or library of molecules) starting from 3D
maps of interaction energies between the molecule and chemical probes |
| TSAR | a fully integrated quantitative
structure-activity relationship (QSAR) package for library design and lead optimization |
| Almond | program specifically developed for
generating and handling alignment independent descriptors called GRIND (GRid INdependent Descriptors). |
| JKlustor | a Java software for diversity
calculations and clustering |
| Software for Molecular Descriptor
Calculation |
Description |
|
|
| ADAPT | a computational model platform developed
for pharmacokinetic and pharmacodynamic applications |
| Dragon | an application for the calculation
of molecular descriptors |
| MolconZ | standard program for generation of Molecular
Connectivity, Shape, and Information Indices for Quantitative Structure Activity Relationship (QSAR) Analyses |
| MOE | integrates tools for computer-assisted drug discovery |
| OpenMolGrid | drug-design using Grid technology |
| VLife MDS | workbench for computer aided drug
design (CADD) and molecule discovery |
| Codessa | advanced, fully featured Quantitative
Structure/Activity Relationship (QSAR) program that ties information from AMPAC<99> and other Quantum Mechanics programs with
experimental data |
| JoeLib | Cheminformatics algorithm library, which was designed for
prototyping, data mining, graph mining, and of course algorithm development |
| CDK | Open source Java computational chemistry package which supports
chemical structure drawing and the graphical layout of 2D chemical structures. |
| PreADMET | Descriptor Calculation, Druglikeness
Prediction: Rule-based Druglike Screening, ADME Prediction: Examination of various ADME properties of drug candidates,
Chemical Library Design: Powerful Workspace, Molecular Set and Molecular Table |
Online Tool for Molecular Descriptor Calculation
| Tools |
Description |
|
|
| PreADMET | a web-based application for predicting
ADME data and building drug-like library using in silico method |
| Molinspiraton | Calculation of Molecular
Properties and Drug-likeness |
| EDragon | application for the calculation of molecular
descriptors |
| MODEL - Molecular Descriptor Lab | Computing
structural and physichemical properties of molecules from their 3D structures. |
Software for file Conversion
| Softwares | Description |
|---|
| Open Babel | an open, collaborative project allowing
anyone to search, convert, analyze, or store data from molecular modeling, chemistry, solid-state materials, biochemistry, or
related areas. |
| EBabel | Interactive Molecular Structure Formats Interconversion
Program |
| VEGA ZZ 2.2.0 | convert several molecular file
formats |
| Galaxy | Input molecule SMILES to generate the 3D
Structure |
Software for Quantum Mechanics
| Softwares | Description |
|---|
| AMPAC 4.0 with GUI | set of tools
to study molecular structure and chemical reactions |
| GAMESS | a general ab initio
quantum chemistry package |
| Gaussian | predicts the energies, molecular structures, and vibrational
frequencies of molecular systems, along with numerous molecular properties derived from these basic computation
types |
| Huckel | Calculates electronic properties of
molecules |
| hmo10 | Huckel molecular orbital calculator |
| Jaguar | Rapid ab initio electronic structure package |
| MOPAC | a semiempirical quantum chemistry program based on Dewar and
Thiel's NDDO approximation |
Web Interface on Libraries
There are number of libraries (e.g. RCDK 0.3.0, RCDK 2.8.1, rpubchem) which provides tools for the serching of molecules from
databases. Though these libraries are powerful but one need expertise in computer. Development of web interfaces over these
libraries are going on in order to provide service to users who have little or no knowledge of computer.
| Links |
Description |
Name | Description | | Cheminformatics | This website
contains links to cheminformatics programs and QSAR datasets. |
|
|
