Mining Large Databases to Find New Leads with Low Similarity to Known Actives: Application to Find New DPP-IV Inhibitors
- 1 June 2019
- journal article
- research article
- Published by Taylor & Francis in Future Medicinal Chemistry
- Vol. 11 (12) , 1387-1401
Abstract
Aim: Fragment-based drug design or bioisosteric replacement is used to find new actives with low (or no) similarity to existing ones but requires the synthesis of nonexisting compounds to prove their predicted bioactivity. Protein-ligand docking or pharmacophore screening are alternatives but they can become computationally expensive when applied to very large databases such as ZINC. Therefore, fast strategies are necessary to find new leads in such databases. Materials & methods: We designed a computational strategy to find lead molecules with very low (or no) similarity to existing actives and applied it to DPP-IV. Results: The bioactivity assays confirm that this strategy finds new leads for DPP-IV inhibitors. Conclusion: This computational strategy reduces the time of finding new lead molecules.Keywords
This publication has 55 references indexed in Scilit:
- High-Throughput 3D Tumor Spheroid Screening Method for Cancer Drug Discovery Using Celigo Image CytometrySLAS Technology, 2017
- Discovery of Novel Ligands for TNF-α and TNF Receptor-1 through Structure-Based Virtual Screening and Biological AssayJournal of Chemical Information and Modeling, 2017
- Drug discovery for male subfertility using high-throughput screening: a new approach to an unsolved problemHuman Reproduction, 2017
- Discovery of 2-((3-cyanopyridin-2-yl)thio)acetamides as human lactate dehydrogenase A inhibitors to reduce the growth of MG-63 osteosarcoma cells: Virtual screening and biological validationBioorganic & Medicinal Chemistry Letters, 2016
- Screening North American plant extracts in vitro against Trypanosoma brucei for discovery of new antitrypanosomal drug leadsBMC Complementary and Alternative Medicine, 2016
- Novel 4-aminoquinazoline derivatives as new leads for anticancer drug discoveryActa Pharmaceutica, 2015
- High-Throughput Screening Platform for Natural Product–Based Drug Discovery Against 3 Neglected Tropical Diseases: Human African Trypanosomiasis, Leishmaniasis, and Chagas DiseaseSLAS Discovery, 2015
- High Throughput Screening for Anti–Trypanosoma cruzi Drug DiscoveryPLOS Neglected Tropical Diseases, 2014
- New natural products as new leads for antibacterial drug discoveryBioorganic & Medicinal Chemistry Letters, 2014
- Amazonian Plant Natural Products: Perspectives for Discovery of New Antimalarial Drug LeadsMolecules, 2013