MMP-14 Inhibitor

Marimastat (BB2516) is a broad spectrum and orally bioavailable inhibitor of MMPs, with potent activity against 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), used in the treatment of cancer. Marimastat (BB2516) is an angiogenesis and metastasis inhibitor, which limits the growth and production of blood vessels. As an antimetatstatic agent it prevents malignant cells from breaching the basement membranes.

KP-457 is a selective a disintegrin and metalloproteinase 17 (ADAM17) inhibitor, with higher selectivity for ADAM17 than for other MMPs and ADAM10, and IC₅₀s are 11.1 nM (ADAM17), 748 nM (ADAM10), 717 nM (MMP2), 9760 nM (MMP3), 2200 nM (MMP8), 5410 nM (MMP9), 930 nM (MMP13), 2140 nM (MMP14), and 7100 nM (MMP17), respectively.

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.

UK 356618 (Compound 4j) is a potent and selective inhibitor of matrix metalloprotease-3 (MMP-3) with an IC₅₀ of 5.9 nM. UK 356618 is less potent against MMP-1, MMP-2, MMP-9, MMP-13 and MMP-14 compared with MMP-3.

ND-336 is a selective inhibitor of matrix metalloproteinase (MMP)-2, MMP-9, and MMP-14, with K_is of 85, 150, and 120 nM, respectively. ND-336 accelerates diabetic wound healing in mice by lowering inflammation and by enhancing angiogenesis and re-epithelialization of the wound.

TMI-1 (WAY-171318) inhibits TNF converting enzyme (TACE) (IC₅₀ of 8.4 nM), ADAM-TS-4, ADAM-17 and various MMPs with oral activity. TMI-1 significantly suppresses the secretion of TNF-α , alleviating collagen-induced arthritis in mice. TMI-1 inhibits cancer cell proliferation, induces apoptosis through a caspase-dependent pathway. TMI-1 also reverses TRPV1 upregulation and lowers the levels of inflammatory factors (TNF-α、IL-1β、IL-6) in nerve cells, protecting against paclitaxel-induced neurotoxicity. TMI-1 leads to changes in pro-atherogenic lipoprotein profiles, but does not affect the progression of early lesions.

BI-4394 (MMP13-IN-3), a chemical probe, is a potent, selective, and orally active MMP-13 inhibitor (IC₅₀=1 nM) for the potential treatment of osteoarthritis. BI-4394 is >1000 selective over other MMPs.

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.

KD014 (DX-2400) is a human monoclonal antibody that selectively targets MMP‑14. KD014 inhibits collagen degradation and regulates the polarization of macrophages toward an anti-inflammatory/anti-tumor phenotype. KD014 alleviates joint damage in rheumatoid arthritis and suppresses tumor growth and invasion. KD014 can be used in studies related to breast cancer and rheumatoid arthritis.

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.

MMP3 inhibitor 1 is a potent and highly selective MMP-3 inhibitor with an IC₅₀ of 1 nM.

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.

Karacoline is an orally active PPARγ activator and ERK/JNK MAPK inhibitor. Karacoline restricts ROS production, maintains mitochondrial membrane potential, and inhibits pulmonary cell apoptosis. Karacoline inhibits NF-κB pathway activation, reduces acetylation levels of p65 and the expression of MMP14 and MMP9, enhances the expression of type II collagen (collagen II) and aggrecan (aggrecan), and suppresses extracellular matrix degradation. In a mouse model of sepsis-induced acute lung injury, Karacoline alleviates lung injury, inhibits the release of IL-1β, IL-6 and TNF-α, increases the Bcl-2/BAX ratio, and reduces caspase 3 expression. Karacoline can be used in research related to acute lung injury and intervertebral disc degeneration.

BPHA is a potent and orally active MMP-2, MMP-9 and MMP-14 inhibitor with IC₅₀s of 12 nM, 16 nM and 17 nM, respectively. BPHA does not inhibit MMP-1, -3, and -7 (the IC₅₀s are 974, >1000, and 795 nM, respectively). BPHA has antiangiogenic and antitumor effects.

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.

(R)-ND-336 is a potent and selective MMP-9 inhibitor with a K_i of 19 nM. (R)-ND-336 inhibits MMP-2 (K_i=127 nM) and MMP-14 (K_i=119 nM). (R)-ND-336 has the potential for diabetic foot ulcers (DFUs) research.

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

ASPH-IN-1 (Compound 14c) is an orally active ASPH inhibitor. ASPH-IN-1 down-regulates MMP2 and MMP14 protein expression. ASPH-IN-1 exhibits anti-cancer activity against cholangiocarcinoma.

3-Aminobenzene-1,2-diol (compound C8) is a matrix metalloproteinase (MMP) inhibitor with IC₅₀ values ​​of 20, 26, 16 and 16.3 μM for MMP-2, MMP-8, MMP-9 and MMP-14, respectively.