Carpenter Richard D, Andrei Mirela, Lau Edmond Y, Lightstone Felice C, Liu Ruiwu, Lam Kit S, Kurth Mark J
Department of Chemistry, University of California, Davis, Davis, CA 95616, USA.
J Med Chem. 2007 Nov 15;50(23):5863-7. doi: 10.1021/jm070790o. Epub 2007 Oct 19.
The cell surface receptor alpha 4 beta 1 integrin, activated constitutively in lymphoma, can be targeted with the bisaryl urea peptidomimetic antagonist 1 (LLP2A). However, concerns on its preliminary pharmacokinetic (PK) profile provided an impetus to change the pharmacophore from a bisaryl urea to a 2-arylaminobenzimidazole moiety, resulting in improved solubility while maintaining picomolar potency [5 (KLCA4); IC50 = 305 pM]. With exceptional solubility, this finding has the potential for improving PK to help diagnose and treat lymphomas.
细胞表面受体α4β1整合素在淋巴瘤中组成性激活，可被双芳基脲拟肽拮抗剂1（LLP2A）靶向。然而，对其初步药代动力学（PK）概况的担忧促使将药效基团从双芳基脲改为2-芳基氨基苯并咪唑部分，从而在保持皮摩尔效力[5（KLCA4）；IC50 = 305 pM]的同时提高了溶解度。鉴于其卓越的溶解度，这一发现有可能改善药代动力学，以帮助诊断和治疗淋巴瘤。
Zotero 插件