MMP-13 Inhibitor

DB04760 is a highly selective, non-zinc-chelating inhibitor of MMP-13 (IC50: 8 nM). DB04760 obviously decreases paclitaxel neurotoxicity and has anticancer activity.

MMP-9 MMP-13 Inhibitor I is a dual inhibitor of MMP-9 and MMP-13 with IC50 of 0.9 nM for both enzymes. It is over 20 times more selective for MMP-9 MMP-13 than for other MMPs.

Marimastat (BB2516) (BB-2516) is a potent, broad spectrum matrix metalloprotease (MMP) inhibitor. MMP-9 (IC50=3 nM), MMP-1 (IC50=5 nM), MMP-2 (IC50=6 nM), MMP-14 (IC50=9 nM)and MMP-7 (IC50=13 nM).

CP-544439 is an orally active and potent MMP-13 inhibitor that prevents diet-induced obesity and inhibits adipogenesis in 3T3-L1 preadipocytes in mice, and can be used for the study of obesity.

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 is an orally active, potent and selective MMP inhibitor with inhibitory effects on MMP-2, MMP-3 and MMP-13.PD-166793 ameliorates myocardial ischemia and reperfusion injury in a rat model of heart failure.PD-166793 is an orally active, potent and selective MMP inhibitor with inhibitory effects on MMP-2, MMP-3, and MMP-13.

XL-784 free base is a selective inhibitor of matrix metalloproteinases (MMP) with IC50 values of ~1900, 0.81, 120, 10.8, 18, and 0.56 nM for MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, and MMP-13, respectively.

XL-784 is a selective inhibitor of matrix metalloproteinases (MMP)(IC50s of ~1900, 0.81, 120, 10.8, 18, 0.56 nM for MMP-1,MMP-2,MMP-3,MMP-8,MMP-9,MMP-13,respectively).

CL-82198, a selective MMP-13 inhibitor, serves as a pharmacological intervention to halt the progression of osteoarthritis (OA). Its mechanism of action involves binding to the S1' pocket of MMP-13, ensuring its selectivity and preventing inhibition of other MMPs.

MMP13-IN-3 is >1000 selective over other MMPs. MMP13-IN-3 is an effective, selective, and orally active MMP-13 inhibitor (IC50=1 nM) for the potential treatment of osteoarthritis.

Tanomastat is an orally bioavailable and non-peptidic biphenyl matrix metalloproteinases inhibitor. For MMP-2, MMP-3, MMP-9, MMP-13 the Ki values are 11, 143, 301, and 1470 nM respectively.

SD-7300 (SC-81490) functions as an orally active inhibitor targeting MMP-2, MMP-9, and MMP-13, exhibiting potent inhibition with K_i values of 0.03, 0.01, and 0.03 nM, respectively. By inhibiting these metalloproteinases, SD-7300 effectively reduces extracellular matrix degradation by tumor cells, thereby curbing their invasion and metastasis. Additionally, this compound acts as a dose-dependent inhibitor of mouse corneal angiogenesis and prevents interleukin-1-induced degradation of bovine cartilage. SD-7300 is applicable in the study of breast cancer.

ALK5-IN-82 is a potent and selective inhibitor of activin receptor-like kinase 5 (ALK5), demonstrating an IC50 value of 9.1 nM. This compound effectively suppresses the expression of α-smooth muscle actin (α-SMA), collagen I, and the proteinases tissue inhibitor of metalloproteinase 1 (TIMP-1) and matrix metalloproteinase 13 (MMP-13) in human umbilical vein endothelial cells induced by transforming growth factor-β. ALK5-IN-82 shows potential for use in research related to cardiac fibrosis.

Broad spectrum MMP inhibitor (IC₅₀ 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.

SD-2590 HCl is an MMP-2,-3, -9, -8, 13, and -14 inhibitor.

WAY-151693 is an inhibitor of human collagenase-3 (MMP-13).

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.

Luteolin 7-O-glucuronide (Luteolin-7-glucuronide) possesses antioxidant activities.

MMPI-1154 is a highly promising imidazole-carboxylic acid (ICA) MMP-2 inhibitor (IC 50 = 6.6 μM) with excellent cardio-cytoprotective properties. It is specifically designed for the study of acute myocardial infarction. Additionally, MMPI-1154 exhibits significant inhibitory effects on MMP-13, MMP-1, and MMP-9 activities with IC 50 values of 1.8 μM, 10 μM, and 13 μM, respectively.

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.

CL 82198 hydrochloride is a selective inhibitor of MMP-13 (89% inhibition at 10μg/mL) that displays no activity at MMP-1, MMP-9 or TACE. Inhibitsin vitroinvasion by the human pituitary adenoma cell line HP75. Rescues paclitaxel induced axon degradation and reduces associated neurotoxicity in zebrafish.

T-26c is a highly potent and selective matrix metalloproteinase-13 (MMP-13) inhibitor with an IC50 of 6.75 pM.