Identification of a novel steroid derivative, NSC12983, as a paclitaxel-like tubulin assembly promoter by 3-D virtual screening.
By flexibly docking 9593 compounds of the NCI-3D database against the refined structure of beta-tubulin using DOCK 4.0, a long-forgotten synthetic steroid derivative, NSC12983, has been identified as a microtubule-stabilizing agent. The 32 top scorers includes NSC12983 and the three added references: paclitaxel, docetaxel and IDN5109. That is, 12.5% of the 0.33% top scorers are active. In addition, NSC12983 is active on Mycobacterium tuberculosis in vitro and in vivo, which might be due to its ability to promote the assembly of essential cell division protein.
Wu
J H
JH
Human Health Research Center, INRS Institut Armand-Frappier, Université du Quebec, Laval, Canada.
Batist
G
G
Zamir
L O
LO
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002784:Cholesterol / Q000031:analogs & derivatives / Q000494:pharmacology*; D003198:Computer Simulation; D016208:Databases, Factual; D015195:Drug Design; D017239:Paclitaxel / Q000494:pharmacology*; D019151:Peptide Library; D013450:Sulfones / Q000494:pharmacology*; D014404:Tubulin / Q000096:biosynthesis*
D000972:Antineoplastic Agents, Phytogenic; C453490:NSC 12983; D019151:Peptide Library; D013450:Sulfones; D014404:Tubulin; D002784:Cholesterol; D017239:Paclitaxel