Pancreatitis

Z-VAD-FMK is a pan-caspase inhibitor and also an ICE-like protease inhibitor, which inhibits apoptosis by preventing the processing of CPP32 to its active form. Z-VAD-FMK sensitivity varies primarily due to differential expression of receptor-interacting protein 1 (RIP1). Z-VAD-FMK limits the cryopreservation-induced apoptosis by reducing caspase-3 activity of in vitro produced bovine embryos. Z-VAD-FMK is immunosuppressive in vitro and inhibits T cell proliferation without blocking the processing of caspase-8 and caspase-3. Z-VAD-FMK leads to a decrease in intracellular glutathione (GSH) with a concomitant increase in reactive oxygen species (ROS) levels in activated T cells. Z-VAD-FMK is due to oxidative stress via the depletion of GSH. Z-VAD-FMK can be used for the study of acute pancreatitis.

Vitamin D3 (Cholecalciferol; Colecalciferol) is a naturally occuring form of vitamin D. Vitamin D3 induces cell differentiation and prevents proliferation of cancer cells.

Chrysin-7-O-glucuronide is a flavonoid found in Scutellaria baicalensis. Chrysin-7-O-glucuronide inhibits α-glucosidase and α-amylase with IC₅₀ values of 612.13 and 980.73 μg/mL. Chrysin-7-O-glucuronide suppresses NF-κB signaling activity. Chrysin-7-O-glucuronide scavenges free radicals, acts as a tight junction protector, and mitigates intestinal mucosal barrier injury. Chrysin-7-O-glucuronide can be used for the research of type 2 diabetes and severe acute pancreatitis-induced intestinal mucosal barrier injury.

Sim-9 is a covalent allosteric inhibitor of interferon regulatory factor 3 (IRF3). Sim-9 binds covalently to the Cys222 residue of IRF3, induces its conformational change, blocks its interactions with TRIF, MAVS and STING, and inhibits IRF3 homodimerization and type I interferon response. Sim-9 exhibits significant anti-inflammatory, organ-protective and survival benefits in mouse models of sepsis and acute pancreatitis. Sim-9 can be used for research related to inflammatory diseases.

AZD5248 is an orally active, selective dipeptidyl peptidase 1 (cathepsin C) inhibitor, with IC₅₀ values of 1 nM and 17 nM against human CatC, 44 nM against human DPP1, and 67 nM against rat DPP1. It exhibits low clearance and high bioavailability in animal models. AZD5248 forms an irreversible covalent bond with the catalytic Cys234 residue of CatC, exerts reversible inhibition via its nitrile moiety, blocks CatC-dependent amyloid formation, and reduces the activation levels of neutrophil serine proteases in bone marrow and blood. AZD5248 reacts with aortic elastin aldehydes to form stable 4-imidazolinones, induces ultrastructural changes in aortic tissue, and has an α-amino acid-based backbone. AZD5248 reduces the severity of acute pancreatitis in mouse models. AZD5248 can be used in research on chronic obstructive pulmonary disease, acute pancreatitis, neurodegenerative diseases, lysosomal storage disorders, acute lung injury, cystic fibrosis, and neutrophil-mediated inflammatory diseases.

MH-06 is an orally active 12-lipoxygenase (ALOX12) PROTAC degrader. MH-06 specifically binds to ALOX12 and recruits E3 ubiquitin ligase to mediate ubiquitination and degradation of the target protein. MH-06 inhibits the MAPK signaling pathway, reduces the production of reactive oxygen species (ROS), restores mitochondrial function, regulates macrophage polarization and decreases the release of pro-inflammatory cytokines. MH-06 can be used for the research of acute pancreatitis.

GSK065 is a KMO inhibitor with an IC₅₀ of 2.5 nM and a K_i of 0.05 nM. GSK065 prevents the effective binding of NADPH to its substrate. GSK065 can be used in studies related to multiple organ dysfunction syndrome associated with acute pancreatitis.

sEH-IN-24 is an orally active soluble epoxide hydrolase (sEH) inhibitor with an IC₅₀ of 1.9 nM. sEH-IN-24 inhibits the pro-inflammatory cytokines TNF-α and IL-6. sEH-IN-24 exhibits anti-inflammatory effects and exerts analgesic activity in vivo. sEH-IN-24 prevents pancreatic edema, inflammation and parenchymal atrophy. sEH-IN-24 can be used for the research of acute pancreatitis.

Paucimannose is a mannosidic N-glycan epitope. It acts as a carcinoembryonic antigen, and a marker for cancer, stem cell properties and inflammation. Paucimannose mainly exists in plants and invertebrates. It consists of oligomannose-type N-glycans that preferentially bind to mannose-binding lectin. Paucimannose localizes on the surface of resting cells and translocates upon cell activation. It can be used in studies related to Pseudomonas aeruginosa infection, cancer and pancreatitis.

KMO-IN-1 is a KMO inhibitor with a mean pIC₅₀ of 8.5 against KMO. KMO-IN-1 can be used in the research of acute pancreatitis.

TRPV4/TRPA1-IN-1 is a TRPV4/TRPA1 inhibitor that suppresses TRPV4/TRPA1-mediated calcium influx. TRPV4/TRPA1-IN-1 alleviates pain behaviors in a mouse trigeminal stimulation pain model and inhibits inflammation and pain-related behaviors in a mouse acute pancreatitis model. TRPV4/TRPA1-IN-1 can be used in research on acute pancreatitis.

Trypsin-IN-2 (Compound 12) is an efficient and highly selective inhibitor of human trypsin, with an IC₅₀ of 8 nM. Trypsin-IN-2 can be used for research on pancreatic cancer.

L-Arginine arginine is the substrate for the endothelial nitric oxide synthase (eNOS) to generate NO. L-Arginine is transported into vascular smooth muscle cells by the cationic amino acid transporter family of proteins where it is metabolized to nitric oxide (NO), polyamines, or L-proline. L-Arginine is a potent vasodilator, and can be used to induce experimental acute pancreatitis.

C3001a is a selective TREK-1 and TREK-2 channel activator with EC₅₀ values of 12.81 μM and 11.31 μM, respectively. C3001a does not affect other two-pore domain K⁺ (K2P) channels. C3001a binds to the cryptic binding site formed by P1 and TM4 in TREK-1. C3001a can be used for the study of pain and pancreatitis.

Glutathione monoethyl ester is a glutathione derivative that can be transported into cells and hydrolyzed into glutathione. Glutathione monoethyl ester downregulates the gene expression of TEN1 and CTC1 while upregulating TERT expression. Glutathione monoethyl ester enhances telomerase activity, promotes proliferation and differentiation in aged bone marrow stromal cells, while elevating glutathione levels and reducing oxidative stress, protein aggregation and cell death in motor neuronal cells. Glutathione monoethyl ester confers broad multi-organ protection against cerebral ischemia, renal injury, liver damage, and pancreatitis. Glutathione monoethyl ester can be used for the research of amyotrophic lateral sclerosis, stroke, acute renal failure, liver injury, and acute pancreatitis.