6jcj

Publication Abstract from PubMed

Microtubules (MTs) is one of the most important proteins in eukaryotic cells and plays a key role in the maintenance of cell morphology and cell division. The discovery and development of small molecule drugs targeting MTs has always been an important direction of anti-cancer research. Nowadays 4-Aryl-4H-chromenes have emerged as potent microtubule-targeting agents (MTAs) for various cancers. Crolibulin, a derivative of 4-Aryl-4H-chromenes, which has been progressed to Phase I/II clinical testing's for anaplastic thyroid cancer with the National Cancer Institute. However, the design and development of 4-Aryl-4H-chromenes family drugs have been hindered for a long time by the lack of structural information of the tubulin-agent complex. Here we report a 2.5A crystal structure of tubulin complexed with crolibulin. This complex structure reveals the interactions between crolibulin and tubulin, helps explain the results of the structure-activity-relationship (SAR) studies and provides a solid structural basis for the design and development of new 4-Aryl-4H-chromenes derivatives as MTAs.

Molecular mechanism of crolibulin in complex with tubulin provides a rationale for drug design.,Zhang Z, Wang C, Ma L, Jiang X, Wu C, Wang Y, Jiang Y, Zheng W, Yang Y, Ma Y, Yang J Biochem Biophys Res Commun. 2019 Apr 2;511(2):381-386. doi:, 10.1016/j.bbrc.2019.02.064. Epub 2019 Feb 22. PMID:30803758^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.