《Discovery of a Covalent Inhibitor of KRASG12C (AMG 510) for the Treatment of Solid Tumors》 was written by Lanman, Brian A.; Allen, Jennifer R.; Allen, John G.; Amegadzie, Albert K.; Ashton, Kate S.; Booker, Shon K.; Chen, Jian Jeffrey; Chen, Ning; Frohn, Michael J.; Goodman, Guy; Kopecky, David J.; Liu, Longbin; Lopez, Patricia; Low, Jonathan D.; Ma, Vu; Minatti, Ana E.; Nguyen, Thomas T.; Nishimura, Nobuko; Pickrell, Alexander J.; Reed, Anthony B.; Shin, Youngsook; Siegmund, Aaron C.; Tamayo, Nuria A.; Tegley, Christopher M.; Walton, Mary C.; Wang, Hui-Ling; Wurz, Ryan P.; Xue, May; Yang, Kevin C.; Achanta, Pragathi; Bartberger, Michael D.; Canon, Jude; Hollis, L. Steven; McCarter, John D.; Mohr, Christopher; Rex, Karen; Saiki, Anne Y.; San Miguel, Tisha; Volak, Laurie P.; Wang, Kevin H.; Whittington, Douglas A.; Zech, Stephan G.; Lipford, J. Russell; Cee, Victor J.. HPLC of Formula: 89466-08-0 And the article was included in Journal of Medicinal Chemistry in 2020. The article conveys some information:
KRASG12C has emerged as a promising target in the treatment of solid tumors. Covalent inhibitors targeting the mutant cysteine-12 residue have been shown to disrupt signaling by this long-“”undruggable”” target; however clin. viable inhibitors have yet to be identified. Here, we report efforts to exploit a cryptic pocket (H95/Y96/Q99) we identified in KRASG12C to identify inhibitors suitable for clin. development. Structure-based design efforts leading to the identification of a novel quinazolinone scaffold are described, along with optimization efforts that overcame a configurational stability issue arising from restricted rotation about an axially chiral biaryl bond. Biopharmaceutical optimization of the resulting leads culminated in the identification of AMG 510, a highly potent, selective, and well-tolerated KRASG12C inhibitor currently in phase I clin. trials (NCT03600883). The experimental part of the paper was very detailed, including the reaction process of 2-Hydroxyphenylboronic acid(cas: 89466-08-0HPLC of Formula: 89466-08-0)
2-Hydroxyphenylboronic acid(cas: 89466-08-0) belongs to acyl phenylboronic acid. Phenylboronic acid (PBA) has been used to extract β-blockers (a class of aminoalcohol-containing drugs) from aqueous solution, rat, and human plasma. HPLC of Formula: 89466-08-0
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