ChemDiv, Inc. introduces the concept of Targeted Diversity which is intended for the design of high quality library of drug-like compounds that have been focused against various biological targets. More than 300 distinct druggable targets selected for universe Targeted Diversity Library (uTDL) design.
The series of multi-targeted libraries were designed besides universe uTDL. These libraries were focused toward GPCRs (particularly, chemokine GPCR), kinases (tyrosine and serine/threonine kinases), etc. This approach underlies in the design of antimitotic, antibacterial, anti- and pro-apoptotic, CNS, anti-inflammatory libraries.
Current TDL is built around 1,000 diverse chemical templates to yield a library of about 50,000 individual drug-like molecules. Embellishment of the library is an ongoing effort at ChemDiv. Regular updates are being made as newly synthesized compounds become available and pass our QA specifications (>90% purity as established by LC/MS with UV and ELSD). Additionally, new proposals for target-specific sets are being evaluated, tested and made available.
The main goal of this approach is to create a thoughtful and multi-purpose diversity and incorporate it into one single compound library for different screening purposes . Thus, the TDL may provide high-quality hits in screening against “difficult” targets with limited or no structure/ligand information, as well as “eclectic” biological targets, including cellular processes (e.g. apoptosis and cell cycle), signaling pathways (e.g. WNT, Hh, RTK and Ras) or protein-protein interactions (e.g. XIAP, pGPCRs).
The selection process for these sets involves identifying active ligands/inhibitors as prototypes existing in the patent and research literature or databases and performing bioisosteric replacement strategies, e.g. a known peptide ligand may be substituted with a small non-peptide peptidomimetic. Then a similarity search based on these strategies is conducted within ChemDiv’s collection for possible augmentation of the rational set. Other techniques include computer-assisted 3-D pharmacophore matching and when possible, in silico docking experiments. The directed synthesis of new chemotypes with functionality mimicking recognition elements (shapes, “warheads”) of known active ligands/inhibitors has also been performed. In some cases, proof of concept has been established with in-house biological data. A special effort has been made to select respective compounds and synthetic templates with good IP potential, as deduced from Beilstein, SciFinder and Markush sub-structure searches. The special rules of ChemDiv’s medchem filters (MCF) ensure the high quality and drug-like properties of selected molecules.