Activators & Inhibitors

Activity: Autophagy inhibitor . Function/Pharmacology: Hydroxychloroquine sulfate is a lysosomotropic agent which inhibits autophagy and triggers apoptosis in a variety of cell types.1,2 Augments the anticancer activity of DNA-damaging chemotherapy.3 Antiinflammatory activity. Decreases cell surface expression of TNFα receptors in U937 cells.4 Hydroxychloroquine sulfate has been used to treat alopecia successfully5 and is a clinically useful antimalaria agent. Cell permeable and active in vivo. Chemical Name: 7-Chloro-4-[4-(N-ethyl-N-b-hydroxyethylamino)-1-methylbutylamino]quinolone sulfate

Activity: Ferroptosis inhibitor . Function/Pharmacology: Inhibits ferroptosis (EC50=60 nM), an iron-dependent form of nonapoptotic cell death1. Potent inhibitor of ferroptosis in cancer cells and glutamate-induced cell death in organotypic rat brain slices1. Blocks the cytotoxic effects of sorafenib in hepatocellular carcinoma cells2. Inhibits oxidative lipid damage and cell death in diverse disease models3. Prevents apoptosis of renal proximal tubular cells induced by reactive oxygen species4. Chemical Name: Ethyl 3-amino-4-(cyclohexylamino)benzoate

Activity: Autophagy inducer . Function/Pharmacology: Negative control for C2-ceramide. Chemical Name: N-Acetyl-D-erythro-sphinganine

Activity: Irreversible 20S proteasome inhibitor . Function/Pharmacology: Epoxomicin is a potent, selective and cell permeable irreversible inhibitor of the 20S proteasome.1 It does not inhibit non-proteasomal proteases such as papain, chymotrypsin, trypsin, calpain and cathepsin B at concentrations up to 50 µM.1 Epoxomicin was isolated from Actinomycete strain Q996-17 and displayed in vivo antitumor activity against B16 melanoma cells.2 Epoxomicin caused a progressive model of Parkinson’s disease in various systems.3,4,5 This model has been disputed.6,7

Activity: DUB inhibitor . Function/Pharmacology: A pan-specific ubiquitin isopeptidase inhibitor. (IC50= 45, 37 and 9.8 μM for USP2, USP7 and SENP2 respectively) Does not effect proteasome proteolytic activity. Induces apoptosis via a Bcl-2-dependent but apoptosome-independent mitochondrial pathway1,2. Cell permeable. Chemical Name: 3,5-Bis[(4-methylphenyl)methylene]-4-piperidone hydrochloride

Activity: SOD mimetic . Function/Pharmacology: Superoxide dismutase (SOD) mimetic. Potent peroxynitrite scavenger but does not scavenge nitric oxide. Chemical Name: Mn(III) meso-Tetra(4-carboxyphenyl)porphine chloride

Activity: PKC inhibitor . Function/Pharmacology: Potent and selective inhibitor of protein kinase C which binds to the regulatory domain (IC50=19 M).1,2 It specifically interacts with the C1 domain of PKC.3 Important tool for assessing the role of PKC in various signaling pathways.4 Cell permeable. Active in vivo.4 Chemical Name: (S)-2,6-Diamino-N-[(1-(1-oxotridecyl)-2-piperidinyl)methyl]hexanamide dihydrochloride hydrate

Activity: PAF receptor antagonist . Function/Pharmacology: Potent and selective antagonist of the platelet activating factor (PAF) receptor (Ki = 16.3 nM)1. Displays an activity profile which includes antiinflamatory, antiangiogenesis and anticancer activity2. Along with leukotriene antagonists, cooperatively provides a robust anti-inflammatory effect regulating PMNL migration and edema formation3. Displays analgesic effects in animal models of neuropathic pain4. Active in vivo. Chemical Name: 4-[3-[4[(2-Chlorophenyl)-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a]diazepin-2-yl]-1-oxopropyl]morpholine

Activity: NAMPT inhibitor . Function/Pharmacology: A potent and selective inhibitor of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the biosynthesis of NAD, which may be used to deplete cells of NAD.1 Displays potent cytotoxic effects in tumor cells.2,3 Displays antitumor activity in vivo.3 Increases ROS levels in cancer cells but not in normal cells.4 Chemical Name: N-[6-(4-chlorophenoxy)hexyl]-N'-cyano-N''-4-pyridinyl-guanidine