Activators & Inhibitors

Activity: Retinoid RARβ/γ agonist . Function/Pharmacology: Stable analog of retinoic acid that acts as a selective agonist for RARß and RARγ. Also inhibits proliferation and induces apoptosis in colorectal cancer cells in culture Chemical Name: 6-[3-(1-Adamantyl)-4-methoxyphenyl]-2-naphthoic acid

Activity: PPARγ agonist . Function/Pharmacology: Prototypical TZD antidiabetic agent. Potent and selective PPARγ agonist (Kd=43 nM).1,2 Clinically useful antihyperglycemc agent.3 Induces a brown fat gene program in subcutaneous white adipose tissue via activation of the PRDM16 protein.4 Induces differentiation of pluripotent stem cells into adipocytes.5 Chemical Name: 5-[[4-[2-(Methyl-2-pyridinylamino)ethoxy]phenyl]methyl]-2,4-thiazolidinedione maleate

Activity: Phosphatase PP2A inhibitor . Function/Pharmacology: Inhibits protein phosphatase 2A (Ki=0.19 μM) and PP1 (Ki=1.1 μM)1. Displays >500-fold selectivity over PP2B. Suppresses growth and migration of PANC-1 pancreatic cancer cells via phosphorylation and degradation of β-catenin2. Arrests G2/M transition via JNK/Sp1-dependent down-regulation of CDK13. Cell permeable. Warning: Avoid skin contact, may cause skin irritation or blistering. Chemical Name: 3α,7α-Dimethylhexahydro-4,7-epoxyisobenzofuran-1,3-dione

Activity: PDE4 inhibitor . Function/Pharmacology: Selective inhibitor of cAMP-specific phosphodiesterase (PDE4), IC50 = 0.2 µM. Displays anti-inflammatory activity. Cell permeable Chemical Name: 4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone

Activity: Cytochrome P450 inhibitor . Function/Pharmacology: Ketoconazole is a broad spectrum antifungal agent which acts via inhibition of a cytochrome P450, CYP51A1 which is a lanosterol 14-demethylase.1 Also inhibits CYP3A and CYP1A1.2 Inhibits adrenal steroidogenesis.3 Downregulates cholesterol synthesis in drug-tolerant human lung cancer cell lines.4 Blocks the biosynthesis of leukotrienes (LT) via inhibition of 5-lipoxygenase and dose dependently inhibits LT-mediated bronchoconstriction in guinea pigs.5 Chemical Name: (±)-1-[4-(4-{[-2-(2,4-Dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-yl]ethan-1-one

Activity: ACAT1 inhibitor . Function/Pharmacology: Tyrosine407 phosphorylation activates mitochondrial acetyl-CoA acetyltransferase 1 (ACAT1) by stabilizing its tetramer. This is believed to be the mechanisms by which ACAT1 is “hijacked” and contributes to the Warburg effect in cancer. Arecoline is a covalent inhibitor of ACAT1 which binds to and disrupts only ACAT1 tetramers (IC50=11.1 μM). ACAT2 and DLAT are not inhibited. Treatment of xenograft nude mice with Arecoline resulted in a dose-dependent reduction in tumor mass.1 Agonist at muscarinic acetylcholine receptors M1 – M5 (EC50 in the range of 7-410 nM).2 May be effective in dementia.3 Chemical Name: 1,2,5,6-Tetrahydro-1-methyl-3-pyridinecarboxylic acid, methyl ester, hydrobromide

Activity: Na channel opener . Function/Pharmacology: A steroidal alkaloid. Voltage-gated Na+ channel activator1. May be used to increase Na+ concentration in cardiomyocytes2 and in cultured sympathetic neurons3. Toxic: LD50=1.35 mg/Kg (mouse i.p.)

Activity: HMG-CoA reductase inhibitor . Function/Pharmacology: A synthetic analog of lovastatin. Blocks cholesterol and isoprenoid biosynthesis via inhibition of HMG-CoA reductase1,2. Induces apoptosis in various cell lines. Causes cell cycle arrest in early G1 phase. Clinically useful antilipemic agent3. Chemical Name: 2,2-Dimethyl-1,2,3,7,8,8a-Hexahydro-3,7-dimethyl-8-[2-(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl]-1-naphthalenyl ester butanoic acid

Activity: VEGFR kinase inhibitor . Function/Pharmacology: ZM-306416 is a VEGF receptor tyrosine kinase inhibitor with selectivity over FGFR-1 (KDR IC50 = 100 nM; FLT IC50 = 2 µM). Chemical Name: 4-[(4'-Chloro-2'-fluoro)phenylamino]-6,7-dimethoxyquinazoline hydrochloride