MMP-12 Inhibitor

Aderamastat (FP-025) is an orally active, selective MMP-12 inhibitor. Aderamastat provides protection against house dust mite (HDM)-sensitized allergic asthma. Aderamastat can be used in the research of respiratory diseases, including chronic inflammatory airway diseases and pulmonary fibrosis.

JG26 is an ADAM inhibitor with IC₅₀ values of 12 nM, 1.9 nM, and 150 nM for ADAM8, ADAM17, and ADAM10, respectively. JG26 inhibits MMP-12 with an IC₅₀ value of 9.4 nM. JG26 inhibits AngII (HY-13948)-induced EGFR transactivation and ERK activation. JG26 increases the expression of ACE2, inhibits the cleavage of CD23, reduces the infection of SARS-CoV-2. JG26 inhibits colorectal cancer metastasis. JG26 can be used for research on Hodgkin lymphoma and vascular diseases.

MMP-7-IN-1 is a highly potent and selective MMP-7 inhibitor with an IC₅₀ of 10 nM. MMP-7-IN-1 can be used in the research of diseases such as cancer and fibrosis.

MMP-7-IN-2 is a potent and selective inhibitor of MMP7 with an IC₅₀ value of 16 nM. MMP-7-IN-2 can be used for the research of diseases such as cancer and fibrosis.

UK-370106 is a potent and highly selective MMP-3 (IC₅₀ of 23 nM) and MMP-12 (IC₅₀ of 42 nM) inhibitor with >1200-fold higher potency than MMP-1, MMP-2, MMP-9, and MMP-14, and about 100-fold than MMP-13 and MMP-8. UK-370106 potently inhibits cleavage of [³H]-fibronectin by MMP-3 (IC₅₀ of 320 nM) and has little effect on keratinocyte migration in vitro.

PI3Kδ-IN-28 is an orally active and selective PI3Kδ inhibitor with an IC₅₀ of 6.1 nM. PI3Kδ-IN-28 inhibits pro-inflammatory M1 macrophage polarization, promotes anti-inflammatory M2 phenotype, and alleviates pulmonary edema and inflammatory infiltration. PI3Kδ-IN-28 is applicable to research related to acute lung injury.

RXP470.1 (RXP-470) is a potent, selective MMP-12 inhibitor with a K_i of 0.2 nM against human MMP-12. RXP470.1 is 2 to 4 orders of magnitude less potent against other MMPs. RXP470.1 significantly reduces atherosclerotic plaque cross-sectional area in mouse. RXP470.1 results in less complex plaques with increased smooth muscle cell:macrophage ratio, less macrophage apoptosis, increased cap thickness, smaller necrotic cores, and decreased incidence of calcification.

MMP408 is a selective and orally effective inhibitor of MMP-12 with IC₅₀ values for human, mouse and rat MMP-12 of 2 nM, 160 nM and 3 μM respectively. MMP408 exhibits IC₅₀ value for human MMP-13 of 120 nM, and its activity against other MMPs is weak. MMP408 can alleviate inflammation, fibrosis and tissue remodeling by inhibiting MMP-12. MMP408 can be used in the research of chronic obstructive pulmonary disease and chronic sinusitis with nasal polyps.

AGG-523 (PF-5212371) is an orally active, reversible, non-hydroxamate, zinc-binding selective inhibitor of ADAMTS4 and ADAMTS5 with IC₅₀ of <0.03 and 0.04 μM. AGG-523 also inhibits MMP-2, -8, 12 activity AGG-523 attenuates release of aggrecanase-generated ARG-aggrecan fragments into synovial fluid, reduces surgery-induced ARG-aggrecan release in rat joint models, and inhibits aggrecanase activity to slow cartilage degradation. AGG-523 can be used for the research of osteoarthritis.

CMC2.24 (TRB-N0224), an orally active tricarbonylmethane agent, is effective against pancreatic tumor in mice by inhibiting Ras activation and its downstream effector ERK1/2 pathway. CMC2.24 is also a potent inhibitor of zinc-dependent MMPs with IC₅₀s ranging from 2.0-69 μM. CMC2.24 alleviates osteoarthritis progression by restoring cartilage homeostasis and inhibiting chondrocyte apoptosis via the NF-κB/HIF-2α axis.

PF-00356231 hydrochloride is a specific, non-peptidic, non-zinc chelating ligand and inhibitor of matrix metalloproteinase MMP-12 (IC₅₀=1.4 μM). PF-00356231 hydrochloride binds to MMP-12 and forms PF-00356231/MMP-12 complex. PF-00356231 hydrochloride shows potency against MMP-13, MMP-8, MMP-9, MMP-3 with IC₅₀s of 0.00065, 1.7, 0.98, 0.39 μM, respectively.

TP0597850 is a selective inhibitor of MMP2 (IC₅₀=0.22 nM). TP0597850 has a long MMP2 dissociation half-life (t_1/2=265 min).

Linvemastat (Compound FC-4) is an orally active MMP-12 inhibitor (IC₅₀: < 10  nM) with high selectivity of MMP-1, -2, -3, -7, -9, -10 and -14. Linvemastat significantly attenuates lung fibrosis in Bleomycin (HY-108345) induced unilateral lung fibrosis mice model and potently reduces kidney damage, interstitial inflammation or fibrosis in kidney fibrosis model of unilateral ureteral occlusion. Linvemastat can be used for inflammatory diseases research, such as idiopathie pulmonary fibrosis (IPF), inflammatory bowel disease (IBD) and asthma.

MMP12-IN-3 (compound 32) is a potent MMP12 inhibitor with an IC₅₀ value of 4.9 nM. MMP12-IN-3 has the potential for the research of chronic respiratory diseases such as emphysema.

AZD1236 is a potent and reversible inhibitor of human MMP-9 and MMP-12.

(R)-MMP408 is an isomer of MMP408 (HY-12093). MMP408 is an orally active MMP-12 inhibitor (IC₅₀=2.0 nM for hMMP-12) that effectively interferes with the epithelial-mesenchymal transition (EMT) process. MMP408 significantly upregulates the expression of E-cadherin in nasal epithelial cells, while inhibiting mesenchymal markers such as vimentin, α-smooth muscle actin and fibronectin, thereby reversing the EMT phenotype. MMP408 is used in studies of airway remodeling-related diseases, including chronic rhinosinusitis with nasal polyps, chronic obstructive pulmonary disease (COPD) and asthma.

CP-544439 is a potent and orally active matrix metalloproteinase-13 (MMP-13) inhibitor with an IC₅₀ of 0.75 nM.

Ageladine A dihydrochloride is an inhibitor of matrix metalloproteinase (MMP) isolated from the marine sponge Agelas nakamurai, possessing anti-angiogenic activity. Ageladine A dihydrochloride not only inhibits MMP-2 but also 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. Additionally, Ageladine A dihydrochloride is a pH-sensitive membrane-permeable dye that emits fluorescence in the blue-green range upon UV excitation, featuring a maximum absorption peak at 370 nm. Furthermore, Ageladine A dihydrochloride serves as a reliable and stable fluorescent pH sensor for detecting changes in intracellular pH values.