Activators & Inhibitors

Activity: ULK1 inhibitor . Function/Pharmacology: A potent and selective inhibitor of the autophagy kinase ULK-1, IC50=108 and 711 nM for ULK1 and 2 respectively.1 Suppresses autophagy induced by mTOR inhibitors and thus synergizes with mTOR inhibitors to induce apoptosis and cell death in tumor cells.1 Chemical Name: 2-((5-Bromo-2-((3,4,5-trimethoxyphenyl)amino)pyrimidin-4-yl)oxy)-N-methylbenzamide

Activity: NEDD8 ligation inhibitor . Function/Pharmacology: A potent and selective NEDD8 ligation inhibitor, IC50=80 nM (in vitro).1 It inhibits the N-terminal acetyl-dependent interaction between the E2 conjugating enzyme UBE2M/UBC12 and DCN1, a subunit of a multiprotein E3 ligase for the ubiquitin-like protein NEDD8, an interaction which is essential for assembly of the multiprotein ligation complex.2 NAcM-OPT inhibits NEDD8 ligation in vitro and in cells (IC50=10 μM) and suppresses anchorage-independent growth of HCC95 cells and is highly selective with respect to other N-terminal acetyl protein binding sites.1 Chemical Name: 1-Benzyl-1-(1-butylpiperidin-4-yl)-3-(3,4-dichlorophenyl)urea

Activity: Endogenous STING agonist . Function/Pharmacology: 2',3'-cGAMP (CAS 1441190-66-4) is an endogenous STING (stimulator of interferon genes) agonist.1 Produced from ATP and GTP via the action of cGMP-AMP synthase (cGAS) which acts as a cytosolic DNA sensor.2,3 Induces autophagy which is a mechanism for clearance of DNA and viruses in the cytosol.4 DNA damage stimulates 2’,3’-cGAMP which stimulates an inflammatory response.5 Chemical Name: Adenylyl-(3’5’)-2’guanylic acid, cyclic nucleotide, disodium salt

Activity: Cannabinoid CB1/CB2 agonist . Function/Pharmacology: High affinity cannabinoid receptor agonist (Ki = 62.3 nM for recombinant human CB1 and 3.3 nM for recombinant human CB2)1 with analgesic2 and anti-inflammatory activities. WIN-55212-2 mesylate activates p42 and p44 MAP kinase via cannabinoid receptor-mediated receptor signaling.3 Chemical Name: (R)-(+)-[2,3-Dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone mesylate

Activity: Cannabinoid CB1 antagonist . Function/Pharmacology: A potent cannabinoid CB1 receptor antagonist with selectivity over CB2 receptors (306-fold).1-3 Displays anorectic effects and antidepressant-like effects in mice.4 Behaves as an agonist at GPR55, EC50=39nM.5 Active in vivo. Chemical Name: N-(Piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide

Activity: Anandamide transport inhibitor . Function/Pharmacology: Inhibits anandamide transport (IC50 = 1 µM) without inhibiting anandamide amidase or activating cannabinoid receptors.1,2 Vanilloid receptors are activated by AM-404.3 Active in vivo.1 Chemical Name: N-(4-Hydroxyphenyl)arachidonamide

Activity: Endogenous cannabinoid . Function/Pharmacology: Endogenous cannabinoid receptor agonist.1-3 Ki=89 nM for CB1 and 371 nM for CB2 receptors. Chemical Name: N-(2-Hydroxyethyl)-5Z,8Z,11Z,14Z-eicosatetraenamide

Activity: L-type Ca channel blocker . Function/Pharmacology: Felodipine is a potent L-type Ca2+ channel blocker that is selective over N-, R-, P/Q- and T-type channels.1,2 It displays high vascular selectivity over cardiac muscle, thus lowering arterial blood pressure without altering cardiac contractility. Felodipine is used in the clinic as an antihypertensive agent. Chemical Name: 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate

Activity: COMT inhibitor - anti-Parkinsons . Function/Pharmacology: Potent catechol O-methyltransferase (COMT) inhibitor (IC50 = 14.3, 20.1 and 73.3 nM for rat liver soluble COMT, total COMT and membrane-bound COMT respectively).1 Increases bioavailability of L-DOPA as adjunct therapy for Parkinson's disease.2 Inhibits α-synuclein aggregation in vitro and inhibits α-synuclein-induced cell death in PC-12 cells3. Antioxidant. Inhibits oxidative stress-induced cell death4. Chemical Name: (2E)-2-Cyano-3-(3,4-dihydroxy-5-nitrophenyl)-N,N-diethyl-2-propenamide