Ser/Thr Protease Inhibitor

Leupeptin hemisulfate is a broad-spectrum protease inhibitor. By inhibiting the activation of the PTEN/PI3K/Akt/NF-κB/ERK1/2/p38 signaling pathway, Leupeptin hemisulfate significantly reduces LPS-induced NO and ROS production, mitochondrial membrane potential hyperpolarization, phagocytic activity, pro-inflammatory cytokine release, and M1 polarization in mouse peritoneal macrophages, and reverses autophagic flux impairment. It also decreases Concanavalin A (HY-P2149)-induced proliferation index of mouse splenic lymphocytes and the Th1/IL-10 and Th2/IL-10 cytokine ratios, thereby modulating innate and adaptive immune responses. Leupeptin hemisulfate inhibits blood coagulation and tumorigenesis in mouse skin. Leupeptin hemisulfate can be used in research on chronic inflammatory diseases and skin tumorigenesis.

PMSF (Phenylmethylsulfonyl fluoride) is a nonspecific and irreversible serine proteases inhibitor. PMSF inhibits some thiol proteases, non-protease enzymes, and acetylcholinesterase. PMSF can be used to prepare protein extracts from tissue and cell lysates.

AEBSF hydrochloride is an irreversible inhibitor of serine proteases, such as chymotrypsin, kallikrein, plasmin, thrombin, and trypsin.

Evolocumab (AMG 145) is a human monoclonal antibody that inhibits PCSK9. Evolocumab is used in the study of hypercholesterolemia and atherosclerotic cardiovascular disease. Evolocumab binds to circulating PCSK9 protein and inhibits its binding to LDLR. Evolocumab has antioxidant and cytoprotective activities against H₂O₂-induced oxidative damage to endothelial cells. Evolocumab may also negatively regulate activation of the TLR-4/NF-κB signaling pathway to prevent inflammation.

Trypsin Inhibitor, soybean is a potent and reversible inhibitor of trypsin.

Imidazole (Glyoxaline; 1,3-Diaza-2,4-cyclopentadiene) is a heterocyclic aromatic compound. Imidazole bearing molecules have been used as corrosion, acetylcholinesterase (AChEI) and xanthine oxidase (XO) inhibitors, performing biological activities such as antifungal, antituberculosis, anti-inflammatory, antioxidant, and analgesic, amongst many others. Imidazole inhibits the enzymatic conversion of the endoperoxides (PGG₂ and PGH₂) to thromboxane A2 by platelet microsomes. Imidazole derivatives exhibits inhibition on SARS-CoV-2 3CL^Pro enzyme, which is promising for research in the field of Alzheimer’s disease, gout, COVID-19 and thrombo-embolic disease.

Bradykinin is an effective endothelium-dependent vasodilator that can lower blood pressure. Bradykinin can induce contraction of bronchial and intestinal non-vascular smooth muscle, increase vascular permeability, and participate in the mechanism of pain.

Nafamostat mesylate (FUT-175), an anticoagulant, is a synthetic serine protease inhibitor. Nafamostat mesylate has anticancer and antivirus effect. Nafamostat mesylate induce apoptosis by up-regulating the expression of tumor necrosis factor receptor-1 (TNFR1). Nafamostat mesylate can be used in the development of the pathological thickening of the arterial wall.

Camostat mesylate (Camostat mesilate) is an orally active, synthetic serine protease inhibitor for chronic pancreatitis. Camostat mesylate, an inhibitor of TMPRSS2, shows antiviral activity against SARS-CoV-2. Camostat mesylate also inhibits the activity of prostasin, trypsin, and matriptase.

α-Methyl-DL-aspartic acid is a specific inhibitor of argininosuccinate synthase (ASS), and also is the rate-limiting enzyme for the recycling of 1-citrulline to 1-arginine.

Benzamidine hydrochloride is a competitive protease inhibitor that blocks the hydrolytic cleavage of glucagon by plasmin, trypsin and thrombin. Benzamidine hydrochloride effectively inhibits the degradation of glucagon by relevant proteases during the collection, storage and analysis of human plasma and blood samples. During in vivo metabolism, Benzamidine hydrochloride undergoes N-hydroxylation and produces multiple metabolites, exhibiting characteristics of delayed excretion or biphasic elimination. Benzamidine hydrochloride only induces slight single-strand DNA breaks at high concentrations and shows no significant genotoxic potential overall. Benzamidine hydrochloride may interfere with the detection of some glucagon antisera, but does not affect key antigen-antibody affinity at specific concentrations. Benzamidine hydrochloride can be used as a stabilizer in glucagon radioimmunoassays to ensure the accuracy and recovery rate of detection results.

Ulinastatin (Uristatin) is a trypsin and serine protease inhibitor. Ulinastatin is the main protein binding inhibitor of various trypsin, chymotrypsin, and various pancreatic proteases. Ulinastatin shows neuroprotective, anti-inflammatory, anti-apoptotic, anti-oxidant effects.

TPCK (L-1-Tosylamido-2-phenylethyl chloromethyl ketone; L-TPCK) is an effective serine protease inhibitor and also a blocker of the PDK1/Akt pathway. TPCK can modify the E7 protein in actively keratinocyte cells. TPCK can induce cellular apoptosis, suppress tumor growth, reduce hypoxic-ischemic brain injury in rat pups, and affect vascular permeability in inflamed rats.

IPR-803 is a potent inhibitor of the uPAR·uPA protein-protein interaction (PPI). IPR-803 binds directly to uPAR with sub-micromolar affinity. IPR-803 displays anti-tumor activity.

UK122 is a potent and selective urokinase-type plasminogen activator (uPA) inhibitor with an IC₅₀ of 0.2 μM. UK122 shows no or little inhibition of tissue-type PA (tPA), plasmin, thrombin, and trypsin (all IC₅₀>100 μM). UK122, 4-oxazolidinone analogue, is an anticancer agent and inhibits cancer cell migration and invasion.

JW480 is a selective KIAA1363/AADACL1 inhibitor with oral activity, featuring IC₅₀ values of 12 nM against human KIAA1363, 20 nM against mouse KIAA1363. JW480 blocks lipid deacetylase activity to restrain HAG metabolism and lowers retinyl ester hydrolase function in hepatic stellate cells. JW480 reduces MAGE lipid levels and inhibits migration, invasion, survival and tumor growth of prostate cancer cells. JW480 lowers PKCδ phosphorylation, facilitates HAGP accumulation, diminishes platelet aggregation, dense granule secretion and Ca²⁺ flux, delays arterial thrombosis and prolongs tail bleeding time in rats. JW480 can be used for the study of prostate cancer and thrombosis.

Benzamidine is a competitive protease inhibitor that blocks the hydrolytic cleavage of glucagon by plasmin, trypsin and thrombin. Benzamidine effectively inhibits the degradation of glucagon by relevant proteases during the collection, storage and analysis of human plasma and blood samples. During in vivo metabolism, Benzamidine undergoes N-hydroxylation and produces multiple metabolites, exhibiting characteristics of delayed excretion or biphasic elimination. Benzamidine only induces slight single-strand DNA breaks at high concentrations and shows no significant genotoxic potential overall. Benzamidine may interfere with the detection of some glucagon antisera, but does not affect key antigen-antibody affinity at specific concentrations. Benzamidine can be used as a stabilizer in glucagon radioimmunoassays to ensure the accuracy and recovery rate of detection results.

WNK1-IN-1 is a selective inhibitor of WNK1 with an IC₅₀ value of 1.6 μM. WNK1-IN-1 inhibits OSR1 phosphorylation with an IC₅₀ value of 4.3 μM. WNK1-IN-1 can be used for the research of blood pressure regulation and cancer.

WNK-IN-11 is an allosteric With-No-Lysine (WNK) kinase inhibitor, with an IC₅₀ of 4 nM for WNK1.

3,4-Dichloroisocoumarin is a potent serine-protease and SrLip inhibitor (K_i for SrLip: 26.6 μM). 3,4-Dichloroisocoumarin is opened by serine proteases and then undergoes acylation with the enzyme, thereby inhibiting protease activity. 3,4-Dichloroisocoumarin can induce DNA fragmentation and Apoptosis. 3,4-Dichloroisocoumarin can be used in the research of multiple fields such as tumors, cardiovascular disease and enzyme catalytic mechanisms.