Digestive System Inflammation

Phorbol 12-myristate 13-acetate (PMA; TPA; Phorbol myristate acetate), a phorbol ester, is a dual SphK and protein kinase C (PKC) activator. Phorbol 12-myristate 13-acetate is a NF-κB activator. Phorbol 12-myristate 13-acetate induces differentiation in THP-1 cells (Validated by MedChemExpress).

Tamoxifen (ICI 47699) is an orally active, selective estrogen receptor modulator (SERM) which blocks estrogen action in breast cells and can activate estrogen activity in other cells, such as bone, liver, and uterine cells. Tamoxifen is a potent Hsp90 activator and enhances the Hsp90 molecular chaperone ATPase activity. Tamoxifen also potent inhibits infectious EBOV Zaire and Marburg (MARV) with IC₅₀ of 0.1 μM and 1.8 μM, respectively. Tamoxifen activates autophagy and induces apoptosis. Tamoxifen can also be dissolved in corn oil (HY-Y1888) for use in inducing gene knockout in CreER transgenic mice. Tamoxifen has better solubility in corn oil compared to Tamoxifen Citrate (HY-13757).

Dexamethasone (Hexadecadrol) is a glucocorticoid receptor agonist, apoptosis inducer, and common disease inducer in experimental animals, constructing models of muscle atrophy, hypertension, and depression. Dexamethasone can inhibit the production of inflammatory miRNA-155 exosomes in macrophages and significantly reduce the expression of inflammatory factors in neutrophils and monocytes. Dexamethasone also has potential for use in COVID-19 research.

Y-27632 is a ROCK inhibitor with K_i values of 220 nM and 300 nM for ROCK1 and ROCK2, respectively. Y-27632 exerts anti-inflammatory and immunomodulatory effects in systemic lupus erythematosus models by inhibiting the ROCK/NF-κB pathway. Y-27632 enhances autophagy by inhibiting the AKT/mTOR pathway, thereby inducing apoptosis apoptosis in oral squamous cell carcinoma. Y-27632 induces the formation of tunneling nanotubes in ARPE-19 cells and significantly enhances mitochondrial transfer through these channels. Y-27632 promotes neurite outgrowth in PC12 cells by activating the Rac1/NOX1/ROS/AKT/PAK1 signaling cascade.

Acetylcysteine (N-Acetylcysteine) is a mucolytic agent that can cross the blood-brain barrier, which reduces the thickness of the mucus. Acetylcysteine is a ROS inhibitor. Acetylcysteine is a cysteine precursor, prevents hemin-induced ferroptosis by neutralizing toxic lipids generated by arachidonate-dependent activity of 5-lipoxygenases. Acetylcysteine induces cell apoptosis. Acetylcysteine also has anti-influenza virus activities. In addition, Acetylcysteine ​​is the most stable form of cysteine ​​during drug delivery and can be used in disulfidptosis studies.

ZDZ-553 is an orally active STAT1 inhibitor with an IC₅₀ value of 0.87 μM. ZDZ-553 modulates STAT1 signaling to affect downstream lipid metabolism and inflammatory pathways. ZDZ-553 attenuates hepatic steatosis in NASH mouse models. ZDZ-553 reduces inflammatory responses in NASH mouse models. ZDZ-553 can be used for the research of nonalcoholic steatohepatitis.

ZY39 is a SaClpP agonist. ZY39 promotes the enzymatic hydrolysis of SaClpP and HsClpP in vitro. ZY39 inhibits the growth of Staphylococcus aureus strains. ZY39 reduces the load of Staphylococcus aureus in organs and ascites in mouse peritonitis models and zebrafish infection models, and improves the survival rate of model animals. ZY39 can be used in studies related to Staphylococcus aureus infection, such as peritonitis.

Y1693 is an orally active RANKL inhibitor with a K_d of 5.03 μM for hRANKL. Y1693 inhibits the activation of the downstream c-fos/NFATc1 signaling pathway by blocking its interaction with RANK. Y1693 significantly inhibits RANKL-induced osteoclast differentiation, F-actin ring formation and bone resorptive activity, while downregulating the mRNA and protein expressions of TRAP, cathepsin K, c-fos and NFATc1. Y1693 shows no obvious cytotoxicity to bone marrow-derived macrophages and osteoclast precursor cells, and exhibits favorable ADME properties. Y1693 improves ovariectomy-induced osteoporosis in mice and reverses ligation-induced periodontal alveolar bone loss. Y1693 is applicable to research related to osteoporosis and periodontal diseases.

Angiotensin II (Angiotensin II) is a vasoconstrictor and a major bioactive peptide of the renin/angiotensin system. Angiotensin II human plays a central role in regulating human blood pressure, which is mainly mediated by interactions between Angiotensin II and the G-protein-coupled receptors (GPCRs) Angiotensin II type 1 receptor (AT1R) and Angiotensin II type 2 receptor (AT2R). Angiotensin II human stimulates sympathetic nervous stimulation, increases aldosterone biosynthesis and renal actions. Angiotensin II human induces growth of vascular smooth muscle cells, increases collagen type I and III synthesis in fibroblasts, leading to thickening of the vascular wall and myocardium, and fibrosis. Angiotensin II human also induces apoptosis. Angiotensin II induces capillary formation from endothelial cells via the LOX-1 dependent redox-sensitive pathway.

SB-431542 is a TGF-β receptor kinase inhibitor (TRKI). SB-431542 has inhibitory activity for ALK4, ALK5 and ALK7 with IC₅₀ values of 1 μM, 0.75 μM and 2 μM, respectively. SB-431542 also inhibits TGF-β-induced transcription, gene expression, apoptosis, and growth suppression. SB-431542 can be used for the research of cancer and signal transduction pathways.

Paclitaxel is a naturally occurring antineoplastic agent and stabilizes tubulin polymerization. Paclitaxel can cause both mitotic arrest and apoptotic cell death. Paclitaxel also induces autophagy.

Retinoic acid is a metabolite of vitamin A that plays important roles in cell growth, differentiation, and organogenesis. Retinoic acid is a natural agonist of RAR nuclear receptors, with IC₅₀s of 14 nM for RARα/β/γ. Retinoic acid bind to PPARβ/δ with K_d of 17 nM. Retinoic acid acts as an inhibitor of transcription factor Nrf2 through activation of retinoic acid receptor alpha.

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.

Olaparib (AZD2281; KU0059436) is a potent and orally active PARP inhibitor with IC₅₀s of 5 and 1 nM for PARP1 and PARP2, respectively. Olaparib is an autophagy and mitophagy activator. Olaparib cannot cross the intact blood-brain barrier (BBB).

Staurosporine is a potent, ATP-competitive and non-selective inhibitor of protein kinases with IC₅₀s of 6 nM, 15 nM, 2 nM, and 3 nM for PKC, PKA, c-Fgr, and Phosphorylase kinase respectively. Staurosporine also inhibits TAOK2 with an IC₅₀ of 3 μM. Staurosporine is an apoptosis inducer.

LY294002 is a broad-spectrum inhibitor of PI3K with IC₅₀s of 0.5, 0.57, and 0.97 μM for PI3Kα, PI3Kδ and PI3Kβ, respectively. LY294002 also inhibits CK2 with an IC₅₀ of 98 nM. LY294002 is a competitive DNA-PK inhibitor that binds reversibly to the kinase domain of DNA-PK with an IC₅₀ of 1.4 μM. LY294002 is an apoptosis activator.

5-Fluorouracil (5-FU) is an analogue of uracil and a potent antitumor agent. 5-Fluorouracil affects pyrimidine synthesis by inhibiting thymidylate synthetase thus depleting intracellular dTTP pools. 5-Fluorouracil induces apoptosis and can be used as a chemical sensitizer. 5-Fluorouracil also inhibits HIV.

Oxaliplatin is a DNA synthesis inhibitor. Oxaliplatin causes DNA crosslinking damage, prevents DNA replication and transcription and induces apoptosis. Oxaliplatin can be used for cancer research.

Etoposide (VP-16; VP-16-213) is an anti-cancer chemotherapy agent. Etoposide inhibits topoisomerase II, thus stopping DNA replication. Etoposide induces cell cycle arrest, apoptosis and autophagy.

Brefeldin A (BFA) is a lactone antibiotic and a specific inhibitor of protein trafficking. Brefeldin A blocks the transport of secreted and membrane proteins from endoplasmic reticulum to Golgi apparatus. Brefeldin A is also an autophagy and mitophagy inhibitor. Brefeldin A inhibits HSV-1 and has anti-cancer activity.