A Multipronged Approach Establishes Covalent Modification of β-Tubulin as the Mode of Action of Benzamide Anti-cancer Toxins was written by Povedano, Juan Manuel;Rallabandi, Rameshu;Bai, Xin;Ye, Xuecheng;Liou, Joel;Chen, Hong;Kim, Jiwoong;Xie, Yang;Posner, Bruce;Rice, Luke;De Brabander, Jef K.;McFadden, David G.. And the article was included in Journal of Medicinal Chemistry in 2020.Quality Control of 3-Chloro-5-nitrobenzoic acid This article mentions the following:
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. In the experiment, the researchers used many compounds, for example, 3-Chloro-5-nitrobenzoic acid (cas: 34662-36-7Quality Control of 3-Chloro-5-nitrobenzoic acid).
3-Chloro-5-nitrobenzoic acid (cas: 34662-36-7) belongs to organic chlorides. Organic chlorides can be used in production of: PVC, pesticides, chloromethane, teflon, insulators.While alkyl bromides and iodides are more reactive, alkyl chlorides tend to be less expensive and more readily available. Alkyl chlorides readily undergo attack by nucleophiles.Quality Control of 3-Chloro-5-nitrobenzoic acid
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics