Lead Drug Screening, Scoring, and Ranking
Lead compounds show pharmacological activity against a biological target and the progressive
optimization of the pharmacological properties. Measurements such as potency, selectivity, solubility,
permeability, metabolic stability, low Cytochrome P450 (CYP) inhibition and good pharmacokinetic (PK)
properties tend to apply across most small-molecule discovery programs, as well as the increasing use of
calculations to confine lipophilicity (logP/ cLogP), molecular weight and a growing number of other
molecular descriptors. Various new guideposts such as ligand efficiency (LE), lipophilic efficiency (LipE),
and lipophilic ligand efficiency (LLE), rotatable bonds and topological polar surface area (TPSA) have also
been introduced. Further assays and computational approaches that attempted to model absorption,
distribution, metabolism, excretion and toxicity (ADMET) are developed. Molecular docking algorithms
are regularly used to virtual screen large numbers of compounds to identify potential leads. In this mode,
parameters of the docking algorithm are often modified to optimize the speed of calculation.
Figure 1 Virtual Screening- improved hit to lead screening process
SOLUTIONS PLATFORM CAREERS
Please input your keywords...
Figure 2 Workflow of Screening
Database screening process, and large libraries of drug-like compounds for screening.
Based on the primary biological activity, and the fate of compounds in later in vivo assays.
Caco-2 evaluation (faster than 22 nm/s) and PAMPA assay data used as filter.
Eliminate spurious hits and artifacts in orthogonal assay.
Homology modeling, molecular Dynamics (MD) simulations, SAR analysis.
Experimental assessment of undesirable off-target activities.
ADMET assays and proper selectivity assays to identify weaknesses within a series of compounds.
Available softwares include PROPKA, H++, SPORES, PDB2PQR, 3D RISM, SZMAP, JAWS, WaterMap,
Further filtering by MW<300, logP<3, number of hyd