MMP Inhibitor

Doxycycline is an orally active, broad-spectrum tetracycline antibiotic that also functions as an MMP inhibitor, exhibiting antibacterial, antiviral, antiparasitic, and antitumor activities. Doxycycline can bind to the classical binding site (CBS) within the mRNA decoding center of the bacterial 70S ribosome's 30S small subunit.Doxycycline blocks bacterial protein synthesis and inhibits the degradation of the extracellular matrix through its interaction with zinc and calcium ions. Doxycycline also inhibits mitochondrial biogenesis, translation, and the expression of respiratory chain proteins. Doxycycline induces apoptosis, inhibits autophagy and EMT, downregulates stem cell markers, and activates the PI3K-AKT pathway, thereby effectively inhibiting the viability and proliferation of cancer cells such as breast cancer cells. Doxycycline can disrupt transthyretin (TTR) amyloid fibrils. Doxycycline also promotes the survival and self-renewal of embryonic stem cells and neural stem cells, and reduces the frequency of medium changes in culture. Doxycycline can be used in research related to cancers—such as breast, prostate, and bladder cancer—as well as neurological disorders.

Doxycycline hyclate (Doxycycline (hydrochloride hemiethanolate hemihydrate); WC2031) is an orally active, broad-spectrum tetracycline antibiotic that also functions as an MMP inhibitor, exhibiting antibacterial, antiviral, antiparasitic, and antitumor activities. Doxycycline hyclate can bind to the classical binding site (CBS) within the mRNA decoding center of the 30S small subunit of the bacterial 70S ribosome.Doxycycline hyclate blocks bacterial protein synthesis and inhibits the degradation of the extracellular matrix through its interaction with zinc and calcium ions. Doxycycline hyclate also inhibits mitochondrial biogenesis, translation, and the expression of respiratory chain proteins. Doxycycline hyclate induces apoptosis, inhibits autophagy and EMT, downregulates stem cell markers, and activates the PI3K-AKT pathway, thereby effectively inhibiting the viability and proliferation of cancer cells such as breast cancer cells. Doxycycline hyclate can disrupt transthyretin (TTR) amyloid fibrils. Doxycycline hyclate also promotes the survival and self-renewal of embryonic stem cells and neural stem cells, and reduces the frequency of medium changes in culture. Doxycycline hyclate can be used in research related to cancers—such as breast, prostate, and bladder cancer—as well as neurological disorders.

T-5224 is a transcription factor c-Fos/activator protein (AP)-1 inhibitor with anti-inflammatory effects, which specifically inhibits the DNA binding activity of c-Fos/c-Jun without affecting other transcription factors. T-5224 inhibits the IL-1β-induced up-regulation of Mmp-3, Mmp-13 and Adamts-5 transcription.

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).

Astragaloside IV, an active component isolated from Astragalus membranaceus, suppresses the activation of ERK1/2 and JNK, and downregulates matrix metalloproteases (MMP)-2, (MMP)-9 in MDA-MB-231 breast cancer cells.

Beta-Sitosterol (purity>98%) is orally active. Beta-Sitosterol exhibits multiple activities, including anti-inflammatory, anticancer, antioxidant, antimicrobial, antidiabetic, antioxidant enzyme, and analgesic. Beta-Sitosterol inhibits inflammation and impaired adipogenesis in bovine mammary epithelial cells by reducing levels of ROS, TNF-α, IL-1β, and NF-κB p65 and restoring the activity of the HIF-1α/mTOR signaling pathway. Beta-Sitosterol induces apoptosis in cancer cells through ROS-mediated mitochondrial dysregulation and p53 activation. Beta-Sitosterol exerts its anticancer effects in cancer cells by activating caspase-3, caspase-8, and caspase-9, mediating PARP inactivation, MMP loss, altered Bcl-2-Bax ratio, and cytochrome c release. Beta-Sitosterol modulates macrophage polarization and reduces rheumatoid inflammation in mice. Beta-Sitosterol inhibits tumor growth in multiple mouse cancer models. Beta-Sitosterol can be used in the research of arthritis, lung cancer, breast cancer and other cancers, diabetes, etc.

Doxycycline hydrochloride is an orally active, broad-spectrum tetracycline antibiotic that also functions as an MMP inhibitor, exhibiting antibacterial, antiviral, antiparasitic, and antitumor activities. Doxycycline hydrochloride can bind to the classical binding site (CBS) within the mRNA decoding center of the 30S small subunit of the bacterial 70S ribosome.Doxycycline hydrochloride blocks bacterial protein synthesis and inhibits the degradation of the extracellular matrix through its interaction with zinc and calcium ions. Doxycycline hydrochloride also inhibits mitochondrial biogenesis, translation, and the expression of respiratory chain proteins. Doxycycline hydrochloride induces apoptosis, inhibits autophagy and EMT, downregulates stem cell markers, and activates the PI3K-AKT pathway, thereby effectively inhibiting the viability and proliferation of cancer cells such as breast cancer cells. Doxycycline hydrochloride can disrupt transthyretin (TTR) amyloid fibrils. Doxycycline hydrochloride also promotes the survival and self-renewal of embryonic stem cells and neural stem cells, and reduces the frequency of medium changes in culture. Doxycycline hydrochloride can be used in research related to cancers—such as breast, prostate, and bladder cancer—as well as neurological disorders.

Edaravone is a strong novel free radical scavenger, and inhibits MMP-9-related brain hemorrhage in rats treated with tissue plasminogen activator.

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.

GW280264X is the mixed ADAM10/TACE (ADAM17) metalloproteinases inhibitor. GW280264X potently blocks TACE (ADAM17) and ADAM10 with IC₅₀s of 8.0 nM and 11.5 nM, respectively. ADAM10 and 17 modulate the immunogenicity of glioblastoma-initiating cells.

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.

o-Phenanthroline (1,10-Phenanthroline), a metal chelator, prevents the induction of chromosomal aberrations in streptozotocin-treated cells. o-Phenanthroline (1,10-Phenanthroline) forms a red chelate with Fe²⁺ that absorbs maximally at 510 nm. o-Phenanthroline (1,10-Phenanthroline) is also a MMP inhibitor.

GI254023X is a potent MMP9 and ADAM10 inhibitor with IC₅₀s of 2.5 and 5.3 nM, respectively.

Isoginkgetin is a pre-mRNA splicing inhibitor inhibitor. Isoginkgetin also inhibits activities of both Akt, NF-κB and MMP-9. Isoginkgetin inhibits the activity of the 20S proteasome, induces apoptosis and activates autophagy.

Chymotrypsin (EC 3.4.21.1; Chymotrypsin A) is an orally effective inhibitor targeting molecules such as TLR4, NF-κB, MMP-1, TNF-α, IL-1β, and IL-6. Chymotrypsin downregulates the TLR4/NF-κB signaling pathway, inhibiting the release of inflammatory factors, reducing cell infiltration and tissue damage. It also reduces the expression of tumor cell adhesion molecules (such as CD44 and CD54) and can be specifically detected by fluorescent probes (such as NBD-3). Chymotrypsin has anti-inflammatory, hepatoprotective, joint damage-reducing, liver protection against lipotoxicity, and anti-tumor metastasis functions. It can be used in research on diseases such as rheumatoid arthritis, non-alcoholic fatty liver disease, and melanoma metastasis. Chymotrypsin can be used in studies of inflammation, edema, and expectoration.

Batimastat is a potent broad spectrum MMP inhibitor with IC₅₀ of 3, 4, 4, 6, and 20 nM for MMP-1, MMP-2, MMP-9, MMP-7 and MMP-3, respectively.

SB-3CT is a potent and competitive matrix metalloproteinase MMP-2 and MMP-9 inhibitor with K_i values of 13.9 and 600 nM, respectively. SB-3CT has high selectivity for gelatinases. SB-3CT shows blood-brain barrier permeability and has neuroprotective effects and anticancer activity.

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.

Stigmasterol is an orally acitve, immunomodulatory agent with anti-inflammatory and neuroprotective effect, as well as able to cross the blood-brain barrier. Stigmasterol activates AMPK, which in turn inhibits NF-κB and NLRP3 signaling pathways, reduces microglia-mediated neuroinflammation, and alleviates cognitive impairment and Alzheimer's disease. Stigmasterol regulates M1/M2 polarization of microglia through the TLR4/ NF-κB pathway, thereby reducing neuropathic pain. Stigmasterol can be used for neurodegenerative diseases, inflammatory diseases, and pain management, among others.

Meloxicam is a non-steroidal antiinflammatory agent that can pass through the blood-brain barrier, inhibits COX activity, with IC₅₀s of 0.49 μM and 36.6 μM for COX-2 and COX-1, respectively.