BMS-813160：一种被选为临床候选药物的强效CCR2和CCR5双重拮抗剂。
BMS-813160: A Potent CCR2 and CCR5 Dual Antagonist Selected as a Clinical Candidate.
作者信息
Cherney Robert J, Anjanappa Prakash, Selvakumar Kumaravel, Batt Douglas G, Brown Gregory D, Rose Anne V, Vuppugalla Ragini, Chen Jing, Pang Jian, Xu Songmei, Yarde Melissa, Tebben Andrew J, Paidi Venkatram Reddy, Cvijic Mary Ellen, Mathur Arvind, Barrish Joel C, Mandlekar Sandhya, Zhao Qihong, Carter Percy H
机构信息
Bristol Myers Squibb Company, Research and Early Development, Princeton, New Jersey 08540-4000, United States.
Biocon Bristol Myers Squibb Research and Development Center, Bangalore 560099, India.
出版信息
ACS Med Chem Lett. 2021 Oct 15;12(11):1753-1758. doi: 10.1021/acsmedchemlett.1c00373. eCollection 2021 Nov 11.
Abstract
BMS-813160 (compound ) was identified as a potent and selective CCR2/5 dual antagonist. Compound displayed good permeability at pH = 7.4 in PAMPA experiments and demonstrated excellent human liver microsome stability. Pharmacokinetic studies established that had excellent oral bioavailability and exhibited low clearance in dog and cyno. Compound was also studied in the mouse thioglycollate-induced peritonitis model, which confirmed its ability to inhibit the migration of inflammatory monocytes and macrophages. As a result of this profile, compound was selected as a clinical candidate.
摘要
BMS-813160（化合物）被鉴定为一种强效且具有选择性的CCR2/5双重拮抗剂。该化合物在pH = 7.4的PAMPA实验中显示出良好的通透性，并在人肝微粒体中表现出优异的稳定性。药代动力学研究表明，其具有出色的口服生物利用度，在犬和食蟹猴体内的清除率较低。该化合物还在小鼠巯基乙酸盐诱导的腹膜炎模型中进行了研究，证实了其抑制炎性单核细胞和巨噬细胞迁移的能力。基于此特性，该化合物被选为临床候选药物。
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