mmp-12

MMP-12 Inhibitor is a selective inhibitor of MMP-12 with IC50s of 2, 160, 320, and 22.3 nM for human, mouse, rat, and sheep MMP-12.

Ilomastat (GM6001) (GM6001, Galardin) is a broad spectrum matrix metalloprotease (MMP) inhibitor.

PF 00356231 is a selectivity inhibitor MMP-12 and can be used in studies about the treatment of emphysema and chronic obstructive pulmonary disease (COPD).

JG26 is a potent inhibitor of ADAM17, which can inhibit ADAM8, ADAM17, ADAM10 and MMP-12, with IC50 values of 12 nM, 1.9 nM, 150 nM and 9.4 nM, respectively, and can be used to study the immune system of the body.

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.

BPHA (MMP-2 MMP-9 Inhibitor II) is a potent, selective and orally active inhibitor of MMP-2, MMP-9 and MMP-14 with IC50s of 12 nM, 16 nM and 17 nM, respectively.BPHA does not inhibit MMP-1, -3 and -7 (IC50s of 974, >1000 and 795 nM, respectively).BPHA has anti-angiogenic and BPHA has anti-angiogenic and anti-tumor activities.

PF-00356231 hydrochloride is an inhibitor of matrix metalloproteinase MMP-12 with IC50 of 1.4 μM.

AS1940477 is p38 MAPK inhibitor. AS1940477 inhibited the enzymatic activity of recombinant p38α and β isoforms but showed no effect against other 100 protein kinases including p38γ and δ isoforms. In human peripheral blood mononuclear cells, AS1940477 inhibited lipopolysaccharide (LPS)- or phytohemagglutinin A (PHA)-induced production of proinflammatory cytokines, including TNFα, IL-1β, and IL-6 at low concentrations (LPS TNFα, IC(50)=0.45n M; PHA TNFα, IC(50)=0.40 nM). In addition, equivalent concentrations of AS1940477 that inhibited cytokine production also inhibited TNFα- and IL-1 β-induced production of IL-6, PGE(2), and MMP-3 in human synovial stromal cells. AS1940477 was also found to potently inhibit TNF production in whole blood (IC(50)=12 nM) and effectively inhibited TNFα production induced by systemically administered LPS in rats at less than 0.1mg kg (ED(50)=0.053 mg kg) with an anti-inflammatory effect lasting for 20h after oral administration. Overall, this stu......

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.

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.

(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.

UK-370106 is a potent and highly selective inhibitor of MMP-3 (IC50: 23 nM) and MMP-12 (IC50: 42 nM), effectively inhibiting the cleavage of [3H]-fibronectin by MMP-3 (IC50: 320 nM).

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.

LXJ-02, a potent inhibitor of EDPs EBP peptide–protein interaction with a K_D of 117 μM for EDPs, activates the macrophage-MMP-12 axis to enhance MMP-12 expression and degrade ECM components like elastin [1].

RXP470 is a potent and selective MMP-12 inhibitor (Ki 0.24 nM).

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].

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.

ARP-100 (MMP-2 Inhibitor III) is a potent and selective matrix metalloproteinase MMP-2 inhibitor (IC50=12 nM). ARP-100 interacts with the S1' pocket of MMP-2 and exhibits anti-invasive properties in an in vitro invasion Matrigel model. ARP-100 has low inhibitory activity against MMP-1 (>50 μM), MMP-3 (4.5 μM), MMP-7 (>50 μM) and MMP-9 (0.2 μM)[1][2].

MMP408 acts as an inhibitor of MMP-12.

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.

Matrix metalloproteinase-3 (MMP-3), also known as stromelysin-1, is a critical enzyme involved in tissue remodeling and repair through its role in degrading extracellular matrix proteins, facilitating cell migration. This enzyme has been implicated in various physiological processes including vascular remodeling associated with aneurysm formation, wound healing, the progression of atherosclerosis, and tumor initiation. MMP-3 inhibitor VIII, a cell-permeable sulfonamide-based hydroxamic acid, effectively inhibits MMP-3 by binding to its active site (Ki = 23 nM), thus blocking its enzymatic activity. Additionally, this inhibitor has been demonstrated to suppress the activity of mouse macrophage metalloelastase MME MMP-12, with an IC50 value of 13 nM, highlighting its potential utility in research on tissue remodeling and disease processes involving MMPs.

Aderamastat (FP-025) is an orally active matrix metalloproteinase 12 (MMP-12) inhibitor used for research in allergic asthma, COPD, and pulmonary fibrosis.