Matrix metalloproteases (MMPs) are the proteolytic enzymes accountable for extracellular matrix (ECM) modification through their Zn2+-dependent catalytic activity. Among these, MMP-12 is one of the crucial MMPs that contributes to various disease states including different types of cancers and other major pathophysiological conditions including COPD, asthma, emphysema, skin diseases, arthritis, vascular diseases, and neurological disorders. The majority of the MMP-12 inhibitors should have three constitutional pharmacophoric features (i.e., a hydrophobic group to occupy the S1′ pocket of the protein, a zinc-binding motif for chelating to the catalytic Zn2+ ion present at the catalytic site, and a flexible and hydrogen bond forming linker region between the S1′ pocket substituent and the zinc chelating group for interacting with the catalytic and Ω-loop amino acid residues). This review mainly focuses on the various roles of MMP-12 in different diseases along with promising and MMP-12-selective inhibitors and molecular modeling studies performed on MMP-12 inhibitors. Therefore, this review will provide comprehensive information to the researchers for designing effective and MMP-12-selective inhibitors for therapeutic advancement in the future.

中文翻译：

---

基质金属蛋白酶-12 （MMP-12） 及其抑制剂：小型综述


基质金属蛋白酶 （MMP） 是通过其 Zn2+ 依赖性催化活性负责细胞外基质 （ECM） 修饰的蛋白水解酶。其中，MMP-12 是导致各种疾病状态的关键 MMP 之一，包括不同类型的癌症和其他主要病理生理状况，包括 COPD、哮喘、肺气肿、皮肤病、关节炎、血管疾病和神经系统疾病。大多数 MMP-12 抑制剂应具有三个结构药效团特征（即，占据蛋白质 S1′ 口袋的疏水基团，用于螯合到催化位点的催化 Zn2+ 离子的锌结合基序，以及 S1′ 口袋取代基和锌螯合基之间的柔性和氢键形成接头区域，用于与催化和 Ω 环氨基酸残基相互作用）。本文主要关注 MMP-12 在不同疾病中的各种作用，以及有前途的 MMP-12 选择性抑制剂和对 MMP-12 抑制剂进行的分子建模研究。因此，本文将为研究人员提供全面的信息，以设计有效的 MMP-12 选择性抑制剂，以在未来的治疗进步。