Activators & Inhibitors

Activity: TRPA1 blocker . Function/Pharmacology: TRPA1 channel blocker IC50=3.1-4.5 μM in various cell lines. Reduces cinnamaldehyde-induced nociception in vivo and blocks cold- and mustard oil-induced activation of mouse TRPA1 but not capsaicin-induced activation. Does not block TRPV1, V2, V3, V4 or M8 at concentrations up to 50 μM.1 Blocks TRPA1 pore dilation (IC50=10.3 μM).2 An important tool for assessing the role of TRPA1 in cell signaling and physiological processes.3-5 Chemical Name: 4-(4-Chlorophenyl)-3-methylbut-3-en-2-oxime

Activity: NFκB inhibitor . Function/Pharmacology: Oxaprozin is a clinically useful non-steroidal anti-inflammatory drug.1 In addition to typical NSAID COX inhibition, Oxaprozin may also exert anti-inflammatory effects via inhibition of the Akt/IKK/NF-kappaβ pathway.2 The compound is capable of inhibiting both anandamide hydrolase in neurons (IC50= 85 µmol/l), with consequent potent analgesic activity, and NF-kappaB activation in inflammatory cells (IC50 = 50 µmol/l).3 Chemical Name: 4,5-Diphenyl-2-oxazolepropanoic acid

Activity: Quinone antioxidant and free radical scavenger . Function/Pharmacology: Analog of coenzyme Q10 which acts as an antioxidant1. Protects mitochondrial membranes against lipid peroxidation and blocks glutamate neurotoxicity in vitro and in vivo2. Increases NGF production with no effect on reactive oxygen species in a cultured rat astrocyte reperfusion injury model3. Extends lifespan and improves motor function in HtrA2 knockout mice4. Chemical Name: 2-(10-Hydroxydecyl)-5,6-dimethoxy-3-methyl-cyclohexa-2,5-diene-1,4-dione

Activity: PDE3A inhibitor . Function/Pharmacology: Cilostazol is a clinically approved phosphodiesterase III (PDE3) inhibitor (IC50 = 0.2 µM) and anti-thrombotic agent. It inhibits platelet aggregation and is a direct arterial vasodilator. Chemical Name: 6-[4-(1-Cyclohexyl-1H-tetrazol-5-yl)-butoxy]-3,4-dihydro-2(1H)-quinolinone

Activity: Glycosidase inhibitor . Function/Pharmacology: Natural product, derived from Castanospermum austral. Potent inhibitor of α- and β-glucosidases.1 Exhibits antiviral properties.2 Inhibits HIV infectivity.3 Inhibits thyroglobulin secretion.4 Castanospermine displays antitumor activity and anti-angiogenic activity.5 Prevents hyperglycemic response to oral glucose load (1 mg/kg) in rats.6 Chemical Name: (1S,6S,7R,8R,8aR)-1,6,7,8-Tetrahydroxyindolizidine

Activity: Apoptosis inducing glucocorticoid . Function/Pharmacology: A synthetic anti-inflammatory glucocorticoid. Induces apoptosis in a variety of cell types1,2. It inhibits proliferation of A549 human lung adenocarcinoma cells and induces cell surface expression of lipocortin-13. Induces osteogenic differentiation of human mesenchymal stem cells4. Induces indoleamine-2,3-dioxygenase (IDO) and exerts IDO-dependent protection in a model of allergic airway inflammation5. Resets and synchronizes circadian clock in cultured cells6. Chemical Name: (11β,16α)-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4-diene-3,20-dione

Activity: Prostaglandin E (EP1) antagonist . Function/Pharmacology: Prostaglandin E2 (EP1 receptor) antagonist (pA2=6.5, guinea pig ileum muscle strip assay )1,4. Possesses analgesic activity in vivo (rodent ED50= 6.8 mg/kg)1,2,4. Does not inhibit COX11 and does not block PGE1 induced hyperalgesia3. Chemical Name: 8-Cholrodibenz(Z)[b,f]oxazepine-10(11H)-carboxylic acid 2-[1-oxo-3-(4-pyridinyl)propyl]hydrazide hydrochloride

Activity: Acetylcholinesterase inhibitor . Function/Pharmacology: Long-acting, centrally active acetylcholinesterase inhibitor, IC50 = 410 nM1. Allosteric potentiator at neuronal nicotinic ACh receptors2. Prevents β-amyloid-induced apoptosis in SH-SY5Y and bovine chromaffin cells3. Clinically useful agent for symptomatic relief of Alzheimer’s disease but fails to prevent progression of the disease4,5. Chemical Name: 4a,5,9,10,11,12-Hexahydro-3-methoxy-11-methyl-6H-benzofuro[3a,3,2-ef][2]benzazepin-6-ol, hydrobromide

Activity: PPARα agonist . Function/Pharmacology: Selective PPARα agonist (EC50=0.63, 32 and >100 µM for PPARα,γ and δ, respectively).1 Displays anti-inflammatory activity2 and reduces LPS-induced inflammation in alveolar epithelial cells3. Induces “browning” of white adipocytes in combined treatment with retinoic acid.4 Stimulates ADAM10-mediated proteolysis of amyloid precursor protein in a mouse model.5 Down regulates NFκB transcriptional activity. Review.6 Chemical Name: 4-Chloro-6-(2,3-xylidino)-2-pyrimidinylthioacetic acid