Activators & Inhibitors

Activity: Ac-CoA carboxylase inhibitor . Function/Pharmacology: Interferes with fatty acid synthase via inhibition of acetyl Co-A carboxylase (ACC1)1. Induces apoptosis in a variety of tumor cell lines2,3. Stimulates neurite outgrowth and neuronal differentiation in rat pheochromocytoma cells4. Impairs glucose-stimulated insulin secretion after chronic treatment5. Chemical Name: 5-(Tetradecyloxy)-2-furoic acid

Activity: Casein kinase 1δ inhibitor . Function/Pharmacology: Potent and selective inhibitor of casein kinase (CK) 1δ., IC50s=0.29, 1.3 and 2.5 μM for δ, ε and α isoforms respectively with no inhibition of CK2. Inhibits CK1δ-mediated phosphorylation and degradation of PER1 protein and lengthens circadian period in U2OS cells.1 Chemical Name: N-(5-Chloro-6-methyl-2-benzothiazolyl)benzeneaceramide

Activity: Myc inhibitor . Function/Pharmacology: Effectively disables c-Myc by inhibiting the c-Myc-Max associationn and function1. It prevents the growth of fibroblasts in a c-Myc-dependent manner. Downregulates human telomerase reverse transcriptase and enhances chemosensitivity in human hepatocellular carcinoma cells2. Induces cell cycle arrest, apoptosis and myeloid differentiation in human acute myeloid leukemia3. Inhibits the MYCN/Max interaction leading to cell cycle arrest, apoptosis and neuronal differentiation in MYCN-amplified neuroblastoma cells4. Chemical Name: 5-[(4-Ethylphenyl)methylene]-2-thioxo-4-thiazolidinone

Activity: Kv7.2/7.3 activator . Function/Pharmacology: A KCNQ2/Q3 (Kv7.2/7.3) activator, EC50=0.38 M (KCNQ1 IC50=15M)1. KCNQ3/Q5 heterodimers are not affected2. Potently dampens neuronal excitability and displays anticonvulsant activity in vivo2. Chemical Name: 4-Chloro-N-(6-chloro-3-pyridinyl)benzamide

Activity: AKT activator . Function/Pharmacology: Akt activator. Binds to the pleckstrin homology domain of Akt preventing membrane translocation but paradoxically activating it in the cytosol. Enhances Akt phosphorylation by upstream protein kinases. Suppresses excitotoxicity-induced neuronal death in vitro and in vivo.1 A useful tool for studying the PI3K/Akt axis.2 Chemical Name: 2-Amino-6-chloro-α-cyano-3-(ethoxycarbonyl)-4H-1-benzopyran-4-acetic acid ethyl ester

Activity: GIRK inhibitor . Function/Pharmacology: Selective GIRK ½ (Kir3.1/3.2) channel activator, IC50 = 160, 887 and 914 nM for GIRK1/2, GIRK1/4 and GIRK1/3 respectively. Has no effect on GIRK2, GIRK2/3, Kir2.1 and Kv7.4 channels.1,2 Displays antiseizure activity2 and decreases anxiety-related behavior without sedative or addictive effects3. Reduces glucose- and IBMX-stimulated GLP-1 secretion with no effect on GIP in murine L and K cells.4 Brain penetrant. Chemical Name: N-(3.4-Difluorophenyl)-n’-(3-methyl-1-phenyl-1H-pyrazol-5-yl)urea

Activity: Nicotinic acetylcholine receptor agonist; cognition enhancer . Function/Pharmacology: Agonist at neuronal nicotinic acetylcholine receptors displaying the highest potency at α4β2 and α2β2 subtypes (EC50= approximately 6 and 11 μM, respectively).1 Displays anxiolytic activity in a rat model and was 6-fold more potent than diazepam.2 Reduces distractibility in a primate model3 and may have relevance in attention deficit hyperactivity disorder4. Improves cognition in Alzheimer’s disease patients.5 Chemical Name: 3-Methyl-5-(1-methyl-2(S)-pyrrolidinyl)isoxazole hydrochloride

Activity: Nrf2 activator . Function/Pharmacology: A novel antioxidant response element (ARE) activator which activates Nrf2 by covalently modifying Keap1 (Kelch-like ECH-associated protein 1) a negative regulator of Nrf2. Modification of Cys151 of Keap1 by AI-1 disrupts the ability of Keap1 to searve as an adaptor for Cul3-Keap1 ubiquitin ligase complex, thereby stabilizing and inducing transcriptional activation of Nrf2. A useful pharmacological tool for probing the involvement of Nrf2 in cellular physiology1. Cell permeable. Chemical Name: 4-Chloro-1,2-dihydro-1-methyl-2-oxo-3-quinolinecarboxylic acid ethyl ester

Activity: Survivin inhibitor . Function/Pharmacology: A novel small molecule survivin suppressant. YM-155 suppresses expression of survivin (a member of the IAP family) and induced apoptosis in human tumor cell lines at 10 nmol/L with little effect on other IAP or Bcl-2 family members.1 Overcomes erlotinib resistance in EGFR mutation-positive non-small cell lung cancer.2 Induces DNA damage.3 Induces an autophagy-dependent cell death in adenoid cystic carcinoma cells.4 Chemical Name: 1-(2-methoxyethyl)-2-methyl-4,9-dioxo-3-(pyrazin-2-ylmethyl)-4,9-dihydro-1H-naphtho[2,3-d]imidazol-3-ium bromide