Nagarajan, Shanthi Skoufias, Dimitrios A. Kozielski, Frank Pae, Ae Nim 2024-01-20T15:04:38Z 2024-01-20T15:04:38Z 2021-09-05 2012-03-22 0022-2623 https://pubs.kist.re.kr/handle/201004/129428 Eg5/KSP is a promising mitotic spindle target for drug discovery in cancer chemotherapy and the development of agents against fungal diseases. A range of Eg5 targeting compounds identified by in vitro or cell-based screening is currently in development. We employed structure-based virtual screening of a database of 700 000 compounds to identify three novel Eg5 inhibitors bearing quinazoline (24) or thioxoimidazolidine (30 and 37) scaffolds. The new compounds inhibit Eg5 ATPase activity, show growth inhibition in proliferation assays, and induce monoastral spindles in cells, the characteristic phenotype for Eg5 inhibiting agents. This is the first successful reported procedure for the identification of Eg5 inhibitors via receptor-ligand interaction-based virtual screening. English AMER CHEMICAL SOC MITOTIC KINESIN KSP CELL-CYCLE BLOCK POTENT INHIBITORS GENETIC ALGORITHM FLEXIBLE DOCKING MITOCHONDRIAL PATHWAY MOLECULAR DOCKING BINDING-AFFINITY DRUG DISCOVERY AML CELLS Receptor-Ligand Interaction-Based Virtual Screening for Novel Eg5/Kinesin Spindle Protein Inhibitors Article 10.1021/jm201290v 1 JOURNAL OF MEDICINAL CHEMISTRY, v.55, no.6, pp.2561 - 2573 JOURNAL OF MEDICINAL CHEMISTRY 55 6 2561 2573 scie scopus 000301767000005 2-s2.0-84858716839 Chemistry, Medicinal Pharmacology & Pharmacy Article MITOTIC KINESIN KSP CELL-CYCLE BLOCK POTENT INHIBITORS GENETIC ALGORITHM FLEXIBLE DOCKING MITOCHONDRIAL PATHWAY MOLECULAR DOCKING BINDING-AFFINITY DRUG DISCOVERY AML CELLS Kinesin spindle protein Eg5 anticancer virtual screening