Highly potent, water soluble benzimidazole antagonist for activated α4β1 integrin
Highly potent, water soluble benzimidazole antagonist for activated α4β1 integrin
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DOI：
10.1021/jm070790o
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发表时间：
2007-11-15
影响因子：
7.3
通讯作者：
Kurth, Mark J.
中科院分区：
文献类型：
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作者：
Carpenter, Richard D.;Andrei, Mirela;Kurth, Mark J.
细胞表面受体α (4) β(1)，整合素，在淋巴瘤中组成性激活，可以用双沙利脲类肽拮抗剂1 （LLP2A）靶向。然而，对其初步药代动力学（PK）谱的担忧促使药效团从双芳基脲段转变为2-芳基氨基苯并咪唑段，从而在保持皮摩尔效价的同时提高溶解度[5 (KLCA4)]；IC50 = 305pm]。由于具有特殊的溶解度，这一发现有可能改善PK，以帮助诊断和治疗淋巴瘤。
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 pharmacokinetc (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.