3-取代吡唑类作为新型 MALT1 蛋白酶别构抑制剂的构效关系研究。
Structure-activity relationship studies of 3-substituted pyrazoles as novel allosteric inhibitors of MALT1 protease.
机构信息
Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan.
Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan.
出版信息
Bioorg Med Chem Lett. 2021 Jun 1;41:127996. doi: 10.1016/j.bmcl.2021.127996. Epub 2021 Mar 26.
We report the discovery of a novel series of 1,5-bisphenylpyrazoles as potent MALT1 inhibitors. Structure-activity relationship exploration of a hit compound led to a potent MALT1 inhibitor. Compound 33 showed strong activity against MALT1 (IC: 0.49 μM), potent cellular activity (NF-κB inhibition and inhibition of IL2 production), and high selectivity against caspase-3, -8, and -9. The results of a kinetics study suggest that compound 33 is a non-competitive inhibitor of MALT1 protein.
我们报告了一种新型的 1,5-双苯并吡唑类化合物的发现，它们是有效的 MALT1 抑制剂。对一个命中化合物的结构-活性关系研究导致了一种有效的 MALT1 抑制剂。化合物 33 对 MALT1（IC：0.49 μM）表现出强烈的活性，具有强大的细胞活性（NF-κB 抑制和抑制 IL2 产生），并且对 caspase-3、-8 和 -9 具有高选择性。动力学研究的结果表明，化合物 33 是非竞争性 MALT1 蛋白抑制剂。
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