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 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.

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.

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.

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.

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 (compound 42) is a potent and selective inhibitor of MMP-2 (matrix metalloproteinases) with an IC50 of 4.2 μM, and it also shows inhibitory activity against MMP-13, MMP-9, and MMP-8 with IC50 values of 12, 23.3, and 25 μM, respectively [1].

(Rac)-Tanomastat ((Rac)-BAY 12-9566) is a racemate of Tanomastat. Tanomastat (BAY 12-9566) is an orally active zinc carboxy-containing inhibitor of non-peptide biphenyl matrix metalloproteinases (MMPs) and inhibits MMP-2 (Ki: 11 nM), MMP-3 (Ki: 143 nM), MMP-9 (Ki: 301 nM), and MMP-13 (Ki: 1470 nM). In several experimental tumor models, Tanomastat exhibits anti-invasive and anti-metastatic effects.

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) is a potent and selective inhibitor of MMP-2 and MMP-13, with IC50 values of 3.6 μM for MMP-2 and 14.6 μM for MMP-13, implicated in osteoarthritis (OA) pathology [1].

TNO211 is a bioactive peptide that functions as a highly soluble fluorogenic substrate for select Matrix Metalloproteinases (MMPs)—specifically MMP-2, 8, 12, 13, and 14. Incorporating a cleavable Gly-Leu bond and an EDANS DABCYL fluorophore quencher pair, TNO211 enables sensitive detection of MMP activity through fluorescence assays, with an absorption emission profile at 340 490 nm. It is particularly effective in analyzing MMPs in culture media from endothelial cells as well as untreated synovial fluid from patients, highlighting its utility in investigations of MMP-associated cellular behaviors, including proliferation, migration (adhesion dispersion), differentiation, angiogenesis, apoptosis, and host defense.

Ageladine A dihydrochloride, derived from the marine sponge Agelas nakamurai, serves as a matrix metalloproteinase (MMP) inhibitor with anti-angiogenic properties. It inhibits MMP-2, MMP-1, MMP-8, MMP-9, MMP-12, and MMP-13, with IC50 values of 4.65 μM, 2.79 μM, 907.12 nM, 1.83 μM, 767.57 nM, and 1.09 μM, respectively. As a pH-sensitive membrane-permeable dye, it emits fluorescence in the blue-green range when excited by ultraviolet light, with a maximum absorption peak at 370 nm. Additionally, Ageladine A dihydrochloride is used as a reliable and stable fluorescent pH sensor to detect intracellular pH changes.