PF-06835919

PF-06835919 is an inhibitor of ketohexokinase C (KHK-C, IC50 = 10 nM). It is selective for KHK-C over KHK-A (IC50 = 170 nM) and a panel of 89 kinases, phosphatases, and receptors at 10 µM. PF-06835919 decreases the levels of fructose-1-phosphate in primary human- and rat hepatocytes (IC50s = 0.232 and 2.801 µM, respectively). It inhibits glucose- and fructose-induced nuclear translocation of carbohydrate-responsive element-binding protein (ChREBP) in a reporter assay using primary rat hepatocytes when used at a concentration of 30 µM. PF-06835919 (10 or 30 mg/kg twice per day) reduces the weight of epididymal adipose tissue, fasting plasma levels of insulin, hepatic levels of triglycerides, and fed- and fasting plasma levels of triglycerides and increases urinary levels of fructose in rats fed a high-fructose diet. It decreases plasma levels of apolipoprotein C3 (ApoC3) and increases plasma levels of adiponectin in rats fed a Western diet when administered at doses of 20 or 60 mg/kg per day.Formal Name: (1alpha,5alpha,6alpha)-3-[2-[(2S )-2-methyl-1-azetidinyl]-6-(trifluoromethyl)-4-pyrimidinyl]-3-azabicyclo[3.1.0]hexane-6-acetic acid. CAS Number: 2102501-84-6. Synonyms: Ketohexokinase Inhibitor 1. Molecular Formula: C16H19F3N4O2. Formula Weight: 356.3. Purity: >98%. Formulation: (Request formulation change), A solid. Solubility: Acetonitrile: Slightly soluble: 0.1-1 mg/ml, DMSO: Sparingly soluble: 1-10 mg/ml. SMILES: OC(C[C@H]1[C@@]2([H])[C@]1([H])CN(C3=NC(N4CC[C@@H]4C)=NC(C(F)(F)F)=C3)C2)=O. InChi Code: InChI=1S/C16H19F3N4O2/c1-8-2-3-23(8)15-20-12(16(17,18)19)5-13(21-15)22-6-10-9(4-14(24)25)11(10)7-22/h5,8-11H,2-4,6-7H2,1H3,(H,24,25)/t8-,9-,10-,11+/m0/s1. InChi Key: MDUYWDNWFXSMJJ-XWLWVQCSSA-N.