Povedano, Juan Manuel published the artcileA Multipronged Approach Establishes Covalent Modification of β-Tubulin as the Mode of Action of Benzamide Anti-cancer Toxins, Application of 1-(3-Cyanophenyl)piperazine, the publication is Journal of Medicinal Chemistry (2020), 63(22), 14054-14066, database is CAplus and MEDLINE.
A phenotypic high-throughput screen identified a benzamide small mol. with activity against small cell lung cancer cells. A “clickable” benzamide probe was designed that irreversibly bound a single 50 kDa cellular protein, identified by mass spectrometry as β-tubulin. Moreover, the anti-cancer potency of a series of benzamide analogs strongly correlated with probe competition, indicating that β-tubulin was the functional target. Addnl. evidence suggested that benzamides covalently modified Cys239 within the colchicine binding site. Consistent with this mechanism, benzamides impaired growth of microtubules formed with β-tubulin harboring Cys239, but not β3 tubulin encoding Ser239. We therefore designed an aldehyde-containing analog capable of trapping Ser239 in β3 tubulin, presumably as a hemiacetal. Using a forward genetics strategy, we identified benzamide-resistant cell lines harboring a Thr238Ala mutation in β-tubulin sufficient to induce compound resistance. The disclosed chem. probes are useful to identify other colchicine site binders, a frequent target of structurally diverse small mols.
Journal of Medicinal Chemistry published new progress about 178928-58-0. 178928-58-0 belongs to piperazines, auxiliary class Piperazine,Nitrile,Benzene, name is 1-(3-Cyanophenyl)piperazine, and the molecular formula is C11H13N3, Application of 1-(3-Cyanophenyl)piperazine.
Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics