Wang, Qinghui; Arnst, Kinsie E.; Wang, Yuxi; Kumar, Gyanendra; Ma, Dejian; Chen, Hao; Wu, Zhongzhi; Yang, Jinliang; White, Stephen W.; Miller, Duane D.; Li, Wei published the artcile< Structural Modification of the 3,4,5-Trimethoxyphenyl Moiety in the Tubulin Inhibitor VERU-111 Leads to Improved Antiproliferative Activities>, Related Products of 4771-48-6, the main research area is trimethoxyphenyl VERU111 synthesis tubulin antitumor.
Colchicine binding site inhibitors (CBSIs) hold great potential in developing new generations of antimitotic drugs. Unlike existing tubulin inhibitors such as paclitaxel, they are generally much less susceptible to resistance caused by the overexpression of drug efflux pumps. The 3,4,5-trimethoxyphenyl (TMP) moiety is a critical component present in many CBSIs, playing an important role in maintaining suitable mol. conformations of CBSIs and contributing to their high binding affinities to tubulin. Previously reported modifications to the TMP moiety in a variety of scaffolds of CBSIs have usually resulted in reduced antiproliferative potency. We previously reported a potent CBSI, VERU-111, that also contains the TMP moiety. Herein, we report the discovery of a VERU-111 analog I that is significantly more potent than VERU-111. The X-ray crystal structure of I in complex with tubulin confirms its direct binding to the colchicine site. In addition, I exhibited a strong inhibitory effect on tumor growth in vivo.
Journal of Medicinal Chemistry published new progress about Antitumor agents. 4771-48-6 belongs to class indole-building-block, and the molecular formula is C10H9NO, Related Products of 4771-48-6.
Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles