MMP-3 Inhibitor

Lixisenatide acetate is a glucagon-like peptide-1 (GLP-1) receptor agonist. Lixisenatide acetate inhibits the inflammatory response through down regulation of pro-inflammatory cytokines, and suppresses of the Akt-MEK1/2 signaling pathway. Lixisenatide acetate can inhibit oxidative stress, mitochondrial dysfunction and apoptosis. Lixisenatide acetate 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.

Tanomastat (BAY 12-9566) is an orally bioavailable, non-peptidic biphenyl matrix metalloproteinases (MMPs) inhibitor with a Zn-binding carboxyl group. The K_i values are 11, 143, 301, and 1470 nM for MMP-2, MMP-3, MMP-9, MMP-13 respectively. Tanomastat shows anti-invasive and antimetastatic activity in several experimental tumor models.

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.

Hydrangenol is an orally active antiphotoaging compound. It can be isolated from Hydrangea serrata leaves. Hydrangenol prevents wrinkle formation by reducing MMP and inflammatory cytokine expression and increasing moisturizing factors and antioxidant genes level.

Prinomastat hydrochloride (AG3340 hydrochloride) 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 hydrochloride 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 hydrochloride can cross blood-brain barrier. Antitumor avtivity.

Cipemastat is a potent, competitive inhibitor of human collagenases 1, 2 and 3 with K_is of 3.0, 4.4 and 3.4 nM, respectively.

CP-471474 is an orally active and pan MMP inhibitor, with IC₅₀ values of 1170 nM (MMP-1), 0.7 nM (MMP-2), 16 nM (MMP-3), 13 nM (MMP-9) and 0.9 nM (MMP-13), respectively.

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

β-Anhydroicaritin is isolated from Boswellia carterii Birdware, has important biological and pharmacological effects, such as antiosteoporosis, estrogen regulation and antitumor properties. β-Anhydroicaritin ameliorates the degradation of periodontal tissue and inhibits the synthesis and secretion of TNF-α and MMP-3 in diabetic rats. β-Anhydroicaritin decreases the overproduction of NO, IL-10, TNF-α, MCP-1 and IL-6 in inperitonitis mice. β-Anhydroicaritin inhibits the elevation of intracellular Ca²⁺, and markedly decreases iNOS protein expression.

XL-784 is a selective matrix metalloproteinases (MMP) inhibitor, with IC₅₀s of ~1900, 0.81, 120, 10.8, 18, 0.56 nM for MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-13, respectively.

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.

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.

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

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.

TAK-756 is a selective transforming growth factor β-activated kinase 1 (TAK1) inhibitor with a target pIC₅₀ of 8.6. TAK-756 can inhibit TAK1 autophosphorylation and downstream NF-κB phosphorylation, suppress the production of inflammatory and catabolic factors such as MMP-3 and IL-6. TAK-756 exhibits anti-inflammatory effects in a rat joint inflammation model. TAK-756 can be used for the research of inflammatory joint disease, osteoarthritis.

MMP3 inhibitor 3 (TFA) is an inhibitor of MMP3. MMP3 inhibitor 3 (TFA) can used to study breast cancer.

CGS 27023A free base is a non-peptidic and orally active MMP inhibitor with the K_i values of 43, 33, 20 and 8 nM for MMP-3, MMP-1, MMP-2 amd MMP-9, respectively. CGS 27023A free base prevents cartilage degradation in stromelysin-induced rabbit cartilage degradation model. CGS 27023A free base can be used for study of arthritis.

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

CGS 27023A is a non-peptidic and orally active MMP inhibitor with the K_i values of 43, 33, 20 and 8 nM for MMP-3, MMP-1, MMP-2 amd MMP-9, respectively. CGS 27023A prevents cartilage degradation in stromelysin-induced rabbit cartilage degradation model. CGS 27023A can be used for study of arthritis.