MMP-7 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.

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.

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).

Isofraxidin, a coumarin component from Acanthopanax senticosus, inhibits MMP-7 expression and cell invasion of human hepatoma cells. Isofraxidin inhibits the phosphorylation of ERK1/2 in hepatoma cells. Isofraxidin attenuates the expression of iNOS and COX-2, Isofraxidinalso inhibits TLR4/myeloid differentiation protein-2 (MD-2) complex formation.

HSP110-IN-1 is a HSP110 inhibitor. HSP110-IN-1 binds to HSP110, inhibits the activity of STAT3, and downregulates the expression of downstream genes VEGF, MMP7 and MMP9. HSP110-IN-1 abrogates IL-6-induced epithelial-mesenchymal transition and inhibits the proliferation of colorectal cancer cells. HSP110-IN-1 remodels the tumor microenvironment by inducing a pro-inflammatory phenotype, regulates macrophages, induces PD-L1 expression, and enhances anti-PD-L1 antibody-mediated tumor regression. HSP110-IN-1 can be used in studies related to colorectal cancer.

Anticancer agent 306 is a spiro tetramic acid derivative and a inhibitor of MMP1, MMP7 and PLK1. Anticancer agent 306 exerts antiproliferative activity against H1299, RKO and MCF-7 cells with IC₅₀ values of 19.25 μM, 3.29 μM and 102.36 μM, respectively. Anticancer agent 306 can up-regulate p21 protein and down-regulate CCND1 and CCNB1 proteins to induce cell cycle arrest, regulate the expression of Bcl-2 and Bax to induce cell apoptosis. Anticancer agent 306 can down-regulate MMP1 and MMP7 proteins to inhibit tumor invasion and metastasis. Anticancer agent 306 can be used for the research of lung cancer, colorectal cancer, breast cancer.

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.

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.

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.

TP0628103 TFA is a potent and highly selective MMP-7 inhibitor with an IC₅₀ of 0.17 nM. TP0628103 TFA undergoes structural optimization via molecular isoelectric point shifting, which reduces organic anion transporter (OAT)-mediated clearance, while maintaining potent MMP-7 inhibitory activity and enhancing MMP subtype selectivity. TP0628103 TFA is applicable for research on the regulatory mechanisms of MMP-7-related matrix metalloproteinases.

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.

PD-166793 is a potent, selective, orally active and wide-broad spectrum inhibitor of MMP, exhibiting nanomolar potency against MMP-2, MMP-3 and MMP-13 (IC₅₀=4, 7, and 8 nM, respectively) and micromolar potency vs MMP-1, -7 and -9 (IC₅₀=6.0, 7.2, and 7.9 μM, respectively). PD-166793 can attenuate left ventricular remodeling and dysfunction in a rat model of progressive heart failure.

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.

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.

MMP-2 Inhibitor II (compound 2) is a selective MMP-2 inhibitor. The Kinetic parameters for MMP inhibition are 2.4 μM (MMP-2), 45 μM (MMP-1), and 379 μM (MMP-7), respectively.

TP0628103 is a potent and highly selective MMP-7 inhibitor with an IC₅₀ of 0.17 nM. TP0628103 undergoes structural optimization via molecular isoelectric point shifting, which reduces organic anion transporter (OAT)-mediated clearance, while maintaining potent MMP-7 inhibitory activity and enhancing MMP subtype selectivity. TP0628103 is applicable for research on the regulatory mechanisms of MMP-7-related matrix metalloproteinases.