mmp-13-in-2

MMP13-IN-2 is a highly potent, selective, and orally active inhibitor of MMP-13. It demonstrates exceptional potency against MMP-13, with an IC50 value of 0.036 nM, and exhibits selectivities greater than 1,500-fold over MMP-1, 3, 7, 8, 9, 14, and TACE. Moreover, MMP13-IN-2 possesses the capability to effectively inhibit collagen release from cartilage in vitro. Consequently, MMP13-IN-2 holds great potential for advancing research on collagenase-related diseases.

Talabostat (PT100, Val-boroPro) is a potent, nonselective and orally available dipeptidyl peptidase IV (DPP-IV) inhibitor with a Ki of 0.18 nM. Talabostat is a nonselective DPP-IV inhibitor, inhibiting DPP8 9, FAP, DPP2 and some other DASH family enzymes essentially as potently as it inhibits DPP-IV[1]. Talabostat stimulates the immune system by triggering a proinflammatory form of cell death in monocytes and macrophages known as pyroptosis. The inhibition of two serine proteases, DPP8 and DPP9, activates the proprotein form of caspase-1 independent of the inflammasome adaptor ASC[2]. Talabostat competitively inhibits the dipeptidyl peptidase (DPP) activity of FAP and CD26 DPP-IV, and there is a high-affinity interaction with the catalytic site due to the formation of a complex between Ser630 624 and the boron of talabostat[3]. Talabostat can stimulate immune responses against tumors involving both the innate and adaptive branches of the immune system. In WEHI 164 fibrosarcoma and EL4 and A20 2J lymphoma models, PT-100 causes regression and rejection of tumors. The antitumor effect appears to involve tumor-specific CTL and protective immunological memory. Talabostat treatment of WEHI 164-inoculated mice increases mRNA expression of cytokines and chemokines known to promote T-cell priming and chemoattraction of T cells and innate effector cells[3]. Talabostat treated mice show significant less fibrosis and FAP expression is reduced. Upon PT100 treatment, significant differences in the MMP-12, MIP-1α, and MCP-3 mRNA expression levels in the lungs are also observed. Treatment with PT100 in this murine model of pulmonary fibrosis has an anti-fibro-proliferative effect and increases macrophage activation[4]. [1]. Connolly BA, et al. Dipeptide boronic acid inhibitors of dipeptidyl peptidase IV: determinants of potencyand in vivo efficacy and safety. J Med Chem. 2008 Oct 9;51(19):6005-13. [2]. Okondo MC, et al. DPP8 and DPP9 inhibition induces pro-caspase-1-dependent monocyte and macrophage pyroptosis. Nat Chem Biol. 2017 Jan;13(1):46-53. [3]. Adams S, et al. PT-100, a small molecule dipeptidyl peptidase inhibitor, has potent antitumor effects and augments antibody-mediated cytotoxicity via a novel immune mechanism. Cancer Res. 2004 Aug 1;64(15):5471-80. [4]. Egger C, et al. Effects of the fibroblast activation protein inhibitor, PT100, in a murine model of pulmonary fibrosis. Eur J Pharmacol. 2017 Aug 15;809:64-72.

PD-166793是一种具有口服活性、有效性和选择性的 MMP 抑制剂，对 MMP-2，MMP-3 和 MMP-13 具有抑制作用。PD-166793 在大鼠心力衰竭模型中改善心肌缺血和再灌注损伤。

MMP13-IN-3 是口服有效的MMP-13选择性抑制剂，IC50为 1 nM，比其他 MMP 的选择性高 1000倍多。MMP13-IN-3在用于骨关节炎方面有研究的价值。

SD-7300 (SC-81490) 作为一种抑制剂，对MMP-2、MMP-9和MMP-13展示出显著的口服活性，其Ki值分别是0.03、0.01和0.03 nM。通过减少肿瘤细胞对细胞外基质的降解，SD-7300有效抑制肿瘤细胞的侵袭与转移。此化合物还能剂量依赖性地抑制小鼠角膜的血管生成，以及抑制由白细胞介素-1诱导的牛软骨的降解。SD-7300常被应用于乳腺癌的相关研究。

Broad spectrum MMP inhibitor (IC_{50< sub> values are 0.7, 0.9, 13, 16 and 1170 nM for MMP-2, MMP-13, MMP-9, MMP-3 and MMP-1 respectively). Attenuates early left ventricular dilation after experimental myocardial infarction in mice.}

MMP-9 inhibitor I is an inhibitor of matrix metalloproteinase-9 (MMP-9) that is selective over MMP-1 and MMP-13 (IC50s = 5, 1,050, and 113 nM, respectively). It also decreases the activity of TNF-α converting enzyme (TACE) in a dose-dependent manner (IC50 = 0.54 μM). MMP-9 inhibitor I decreases TNF-α secretion stimulated by LPS in BV-2 microglial cells when used at concentrations of 50 and 100 μM.

Highly potent and selective MMP13 inhibitor (IC50 = 6.9 pM). Exhibits >2600-fold selectivity for MMP13 over related MMPs. Inhibits degradation of bovine nasal septum cartilage explants in vitro . Orally bioavailable. Nara et al (2014) Thieno[2,3-d]pyrimidine-2-carboxamides bearing a carboxybenzene group at 5-position: highly potent, selective, and orally available MMP-13 inhibitors interacting with the S1 binding site. Bioorg.Med.Chem. 22 5487 PMID:25192810

GM 1489 is a broad-spectrum inhibitor of matrix metalloproteinases (MMPs) with Ki values of 0.002, 0.1, 0.5, 0.2, and 20 μM for MMP-1, MMP-8, MMP-2, MMP-9, and MMP-3, respectively. It reduces 5-aza-2'-deoxycytidine-induced increases in MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, and MMP-14 expression as well as cell invasion in AsPC-1, BxPC-3, Hs766T, MiaPaCa2, and PANC-1 cancer cells. Topical administration of GM 1489 (100 μg) inhibits increases in ear thickness and epidermal hyperplasia induced by phorbol 12-myristate 13-acetate and phorbol dibutyrate (PdiBu) in mice.

MMP2-IN-2 是一种具有选择性的 MMP-2 (基质金属蛋白酶)抑制剂，具有潜在的抗癌抗肿瘤活性，抑制 MMP-13、MMP-9 和 MMP-8，可用于研究癌症和免疫疾病。

Rac)-Tanomastat ((Rac)-BAY 12-9566) 是 Tanomastat 的外消旋体。其中 Tanomastat (BAY 12-9566) 是一种口服具有活力的、含锌羧基的非肽联苯基质金属蛋白酶(MMPs)抑制剂，能够抑制 MMP-2 (Ki: 11 nM)、MMP-3 (Ki: 143 nM)、MMP-9 (Ki: 301 nM)、MMP-13 (Ki: 1470 nM)。在几种实验性肿瘤模型中，Tanomastat 表现出抗侵袭和抗转移作用。

AZD1236 is a potent and reversible inhibitor of human MMP-9 and MMP-12 (IC50 = 4.5 and 6.1nM, respectively), with >10-fold selectivity to MMP-2 and MMP-13 and >350-fold selectivity to other members of the enzyme family. AZD1236 activity is approximately 20 to 50-fold lower at the rat, mouse, and guinea pig orthologues. In acute models of lung injury, AZD1236 inhibited the haemorrhage and inflammation induced by instillation of human MMP-12 into rat lungs by ~80% at 0.81mg kg, and also abolished macrophage infiltration into BAL fluid induced by tobacco smoke inhalation in the mouse.

MMP13-IN-5 (compound 13m) 作为具有针对性的MMP-2 MMP-13 抑制剂，显示出高效的抑制活性（IC50=3.6 μM 14.6 μM），适用于骨关节炎疼痛的研究。

TNO211为具备生物活性的肽，主要研究对象是基质金属蛋白酶（MMP），一类能够降解多种细胞外基质蛋白并调控诸多生物活性分子的肽链内切酶家族。MMP在细胞表面受体裂解、凋亡配体释放及趋化因子 细胞因子失活等过程中起作用，同时与细胞增殖、迁移（粘附 分散）、分化、血管生成、细胞凋亡及宿主防御等生物行为密切相关。TNO211可靶向MMP-2、8、12、13和14，包含MMP特定可裂解的Gly-Leu键，并具有EDANS DABCYL荧光标记，其荧光检测在监测内皮细胞培养基和患者滑液中的MMP活性方面表现出高灵敏度。吸光度 电磁场测量参数为340 490 nm。

Ageladine A dihydrochloride 是一种从海洋海绵Agelas nakamurai中提取的基质金属蛋白酶 (MMP) 抑制剂，并具有抗血管生成特性。它能抑制MMP-2、MMP-1、MMP-8、MMP-9、MMP-12和MMP-13，其IC50值为4.65 μM、2.79 μM、907.12 nM、1.83 μM、767.57 nM和1.09 μM。作为pH敏感的膜通透性染料，Ageladine A dihydrochloride在紫外线激发下呈现蓝绿色荧光，最大吸收峰为370 nm。此外，它作为一种稳定的荧光 pH 传感器，可用于监测细胞内pH值的变化。