Activators & Inhibitors

Activity: HDAC8 activator . Function/Pharmacology: Highly potent and isozyme selective activator of recombinant HDAC8. Increases the activity of HDAC8 by a factor of 12 at 10 μM. No activation of other HDACs is observed. Rescues the activity of catalytically compromised HDAC8 mutants in vitro.2 Chemical Name: 1-Benzoyl-3-phenyl-2-thiourea

Activity: Mitochondrial import inhibitor . Function/Pharmacology: Attenuates mitochondrial protein import (4-10 M). Discovered in a screen of FDA-approved drugs. Blocks translocation of a mutant form of alanine: glyoxylate aminotransferase (AGT) to the mitochondria and restores AGT trafficking to peroxisomes.1 Also reduces oxalate accumulation and thus has potential to treat patients with primary hyperoxaluria 1 who possess mutations in AGT.1 Also displays antimicrobial activity2, inhibits apamin-sensitive K+ channels3 and induces apoptosis by inhibiting XIAP4. Chemical Name: 1,1’-Decamethylenebis(4-aminoquinaldinium)dichloride

Activity: p75NTR ligand / Promotes Neurogenesis . Function/Pharmacology: A nonpeptide neurotrophic factor receptor p75 (p75NTR) agonist which promotes survival signaling in neurotrophin-responsive cells.1 Promotes functional recovery in a mouse model of spinal contusion injury.2 Protects neurogenesis after traumatic brain injury.3 Reverses cholinergic neurite dystrophy in Alzheimer’s disease mouse models.4 Stabilizes neuronal calcium, preserves mitochondrial movement and protects against HIV-associated neuropathogenesis.5 Orally active and blood-brain barrier permeant. Chemical Name: (2S,3S)-2-Amino-3-methyl-N-[2-(4-morpholinyl)ethyl]pentanamide, dihydrochloride

Activity: Alkaline phosphatase inhibitor . Function/Pharmacology: Potent alkaline phosphatase inhibitor.1 Strongly activates cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels by inhibiting a membrane associated protein phosphatase.2 Inhibits terminal cell division-associated differentiation in murine erythroleukemia cells.3 Chemical Name: (-)-(S)-6-(4-Bromophenyl)-2,3,5,6-tetrahydroimidazo[2,1-b]thiazole oxalate

Activity: JNK inhibitor . Function/Pharmacology: Inhibits JNK2 and JNK3 via binding to the ATP binding domain. Displays little or no activity against JNK1, p38 and a panel of 30 other kinases.1 Induces prometaphase arrest-dependent apoptotic cell death in human Jurkat T cells.2 Chemical Name: N-(3-Cyano-4,5,6,7-tetrahydrobenzo[b]thien-2-yl)-1-naphthalenecarboxamide

Activity: JAK2 inhibitor . Function/Pharmacology: A remarkably potent and selective JAK2 inhibitor (IC50 = 60 nM). Displays no effect on Src and TYK2 tyrosine kinase activity at a concentration of 25 μM1. Suppresses JAK2-V617F-mediated human pathological cell growth in vitro and in vivo2 and is concomitant with the disruption of intracellular vimentin filaments3. Reduces the tumorigenic potential of T98G glioblastoma cells in vitro and in vivo4. Chemical Name: E-4,4’-(1,2-Diethyl-1,2-ethenediyl)bis[2-[(diethylamino)methyl]phenol

Activity: GPR40 antagonist . Function/Pharmacology: A GPR40 receptor antagonist1. Suppresses fatty acid-induced elevation of intracellular Ca++. Inhibits palmitic acid potentiated glucose–stimulated insulin secretion in Min6 pancreatic β cells in vitro. Lowers serum insulin levels, increases insulin sensitivity2 in obese Zucker rats (6 mg/kg)2. Reduces pancreatic β cell apoptosis in obese diabetic (db/db) rats3. Protects Min6 β cells from palmitic acid-induced ER stress and apoptosis4 Chemical Name: N-(4-Butylphenyl)-4-fluorobenzenesulfonamide

Activity: HECT domain containing E3 ubiquitin ligase inhibitor . Function/Pharmacology: The first small molecule inhibitor of the HECT domain-containing E3 ubiquitin ligases. Heclin (HECT ligase inhibitor) inhibits several HECT ligases in cultured cells, IC50s = 6.8, 6.3 and 6.9 M for Smurf2, Nedd4 and WWP1 respectively. It does not block E2 binding but causes a conformational change which results in oxidation of the active site cysteine. Cells tolerate heclin treatment for several hours but exposure for 24 hours leads to death in HEK293 cells, consistent with an essential role for HECT ligase activity in mammalian cells. Heclin does not inhibit RING domain ligases.1 Thus it is a valuable tool for distinguishing between RING and HECT-mediated ubiquitination. Prevents proteasomal degradation of thioredoxin-interacting protein after microbial infection with subsequent reduction of pro-inflammatory mediators.2 Improves short-term memory, consolidation, retrieval and reconsolidation of co