MMP-3 Inhibitor

Ilomastat (GM6001) is a potent and broad spectrum matrix metalloprotease (MMP) inhibitor, inhibits MMPs (IC₅₀s, 1.5 nM for MMP-1; 1.1 nM for MMP-2; 1.9 nM for MMP-3; 0.5 nM for MMP-9), with a K_i of 0.4 nM for human skin fibroblast collagenase (MMP-1).

Cordycepin (3'-Deoxyadenosine) is a nucleoside derivative and inhibits IL-1β-induced MMP-1 and MMP-3 expression in rheumatoid arthritis synovial fibroblasts (RASFs) in a dose-dependent manner. Cordycepin kills Mycobacterium tuberculosis through hijacking the bacterial adenosine kinase.

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.

DC-Y13-27 is a DC-Y13 derivative and YTHDF2 inhibitor (K_D: 37.9 μM). DC-Y13-27 inhibits YTHDF2, restores FOXO3 and TIMP1 protein levels, and reduces MMP1/3/7/9 expression. DC-Y13-27 induces Pyroptosis and increases IL-1β secretion. DC-Y13-27 reduces intervertebral disc degeneration and enhances the response to radiotherapy in colon cancer and melanoma. DC-Y13-27 has antitumor activity against breast cancer.

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.

COX-2/5-LOX-IN-8 is an orally active dual COX-2/5-LOX inhibitor, with an IC₅₀ of 6.30 μM against sheep-derived COX-2 and an IC₅₀ of 8.09 μM against 5-LOX. COX-2/5-LOX-IN-8 acts as a membrane stabilizer that stabilizes erythrocyte membranes against hypotonicity-induced hemolysis. COX-2/5-LOX-IN-8 functions as a protein stabilizer that inhibits heat-induced denaturation of bovine serum albumin. COX-2/5-LOX-IN-8 reduces paw swelling, improves hind limb weight-bearing function, decreases serum levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, CRP), and lowers serum levels of cartilage degradation biomarkers (COMP, MMP-3, CTX-II). COX-2/5-LOX-IN-8 can be used in the research of osteoarthritis.

F81-1144b is a MMP-1 and MMP-3 inhibitor with IC₅₀ values of 5 nM and 29 nM, respectively. F81-1144b reduces serum and hepatic triacylglycerol levels, decreases the secretion of very-low-density lipoprotein-triacylglycerol, inhibits de novo hepatic fatty acid synthesis, and lowers serum insulin and glucose levels. F81-1144b can be used for the research of hypertriglyceridemia.

Lixisenatide is a glucagon-like peptide-1 (GLP-1) receptor agonist. Lixisenatide inhibits the inflammatory response through down regulation of pro-inflammatory cytokines, and suppresses of the Akt-MEK1/2 signaling pathway. Lixisenatide can inhibit oxidative stress, mitochondrial dysfunction and apoptosis. Lixisenatide can be used for the researches of inflammation, metabolic disease, neurological disease and cardiovascular disease, such as rheumatoid arthritis, diabetes, Alzheimer's disease and atherosclerosis.

ARP-100 is a potent and selective matrix metalloproteinase MMP-2 inhibitor (IC₅₀=12 nM). ARP-100 interacts with S1＇ pocket of MMP-2 and shows anti-invasive properties in an in vitro model of invasion on matrigel. ARP-100 shows the less inhibitory activity towards MMP-1 (>50 μM), MMP-3 (4.5 μM), MMP-7 (>50 μM), and MMP-9 (0.2 μM).

Apigenin-7-glucuronide could inhibit Matrix Metalloproteinases (MMP) activities, with IC₅₀s of 12.87, 22.39, 17.52, 0.27 μM for MMP-3, MMP-8, MMP-9, MMP-13, respectively.

Luteolin 7-O-glucuronide could inhibit Matrix Metalloproteinases (MMP) activities, with IC₅₀s of 17.63, 7.99, 11.42, 12.85, 0.03 μM for MMP-1, MMP-3, MMP-8, MMP-9, MMP-13, respectively.

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.

Phellodendrine chloride is an orally active plant alkaloid. Phellodendrine chloride inhibits the proliferation of KRAS-mutated pancreatic cancer cells by suppressing macropinocytosis and glutamine metabolism, inducing ROS accumulation and mitochondrial apoptosis. Phellodendrine chloride promotes autophagy by activating the AMPK/mTOR pathway, alleviating intestinal damage in ulcerative colitis. Phellodendrine chloride can alleviate gouty arthritis by inhibiting the IL-6/STAT3 signaling pathway. Phellodendrine chloride suppresses allergic reactions by altering the conformation of MRGPRB3/MRGPRX2 protein, thereby inhibiting the activation of PKC and subsequent downstream MAPK and NF-κB signaling. Phellodendrine chloride inhibits the AKT/NF-κB pathway and down-regulates the expression of COX-2, thereby protecting zebrafish embryos from oxidative stress. Phellodendrine chloride has an anti-major depressive disorder (MDD) effect by down-regulating CHRM1, HTR1A, and the PI3K/Akt signaling pathway.

Prinomastat (AG3340) is a broad spectrum, potent, orally active metalloproteinase (MMP) inhibitor with IC₅₀s of 79, 6.3 and 5.0 nM for MMP-1, MMP-3 and MMP-9, respectively. Prinomastat inhibits MMP-2, MMP-3, MMP-13 and MMP-9 with K_is of 0.05 nM, 0.3 nM, 0.03 nM and 0.26 nM, respectively. Prinomastat crosses blood-brain barrier. Antitumor avtivity.

MMP13-IN-2 is a potent, selective and orally active MMP-13 inhibitor. MMP13-IN-2 exhibits excellent potency for MMP-13 (IC₅₀=0.036 nM) and selectivities (greater than 1,500-fold) over MMP-1, 3, 7, 8, 9, 14, and TACE. MMP13-IN-2 has the ability to block the release of collagen from cartilage in vitro. MMP13-IN-2 has the potential for collagenase related disease research.

MMP Inhibitor II (compound 4e) is a potent, reversible pan-MMP inhibitor with IC₅₀ values of 24 nM, 18.4 nM, 30 nM, and 2.7 nM for MMP-1,MMP-3, MMP-7, and MMP-9, respectively.

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.

MMP-9/MMP-13 Inhibitor I is a potent MMP-9 and MMP-13 inhibitor with IC₅₀s of both 0.9 nM. MMP-9/MMP-13 Inhibitor I shows >20-folds selectivity for MMP-9/MMP-13 over other MMPs.

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.