Jia Hong, Guo Yan-shen, Ge Yi-yu, Wen Hui, Yang Jing, Yang Xiu-ying, Du Guan-hua, Yang Guang-zhong
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union'Medical College, Beijing 100050, China.
Yao Xue Xue Bao. 2007 Dec;42(12):1271-81.
A novel inhibitor series for matrix metalloproteinases (MMPs) were designed and synthesized. Using succinate and malonate as zinc binding groups and long hydrophobic substituents to bind with S1' pockets, the compounds showed micromolar inhibition and selectivity for MMP-2 over others. And we found a better activity compound. It is a chance to find a better precursor of MMP-2 inhibitors with activity and bioavailability by further optimization of compounds.
设计并合成了一种新型的基质金属蛋白酶（MMPs）抑制剂系列。该化合物以琥珀酸和丙二酸作为锌结合基团，并带有长链疏水取代基与S1'口袋结合，对MMP-2表现出微摩尔级别的抑制作用，且对其他酶具有选择性。我们还发现了一种活性更好的化合物。通过进一步优化化合物，有望找到一种兼具活性和生物利用度的更好的MMP-2抑制剂前体。
