P053

P053 is an inhibitor of ceramide synthase 1 (CerS1, IC50s = 0.54 and 0.46 µM for human and mouse CerS1, respectively). It is selective for CerS1 over CerS2, CerS4, CerS5, and CerS6 (IC50s = 28.6, 17.2, 7.2, and 11.4 µM, respectively). P053 decreases the production of C18 ceramide (Cay-19556) from dihydrosphingosine in cortical neuron cultures in a concentration-dependent manner. It also lowers levels of C18 ceramide, C18 galactosylceramide, and C18:0 and 18:1 sphingomyelin species in HEK293 cells, when used at concentrations ranging from 30 to 300 nM, without inducing cell death. P053 (5 mg/kg) decreases endogenous C18 and C18:2/18:0 ceramide levels and increases C22:0 (Cay-22533), C24:0 (Cay-62535), and C24:1 ceramide (Cay-62530) levels in mouse skeletal muscle. It increases fatty acid oxidation in mouse skeletal muscle and inhibits triglyceride synthesis and increases in white adipose mass in a model of high-fat diet-induced obesity but does not affect insulin resistance.Formal Name: (betaS)-beta-amino-4-[(3,4-dichlorophenyl)methoxy]-beta-methyl-benzenebutanol. CAS Number: 2748196-63-4. Molecular Formula: C18H21Cl2NO2. Formula Weight: 354.3. Purity: >95%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 30 mg/ml, DMSO: 30 mg/ml, Ethanol: 30 mg/ml. lambdamax: 225 nm. SMILES: ClC1=C(Cl)C=C(COC2=CC=C(CC[C@@](N)(C)CO)C=C2)C=C1. InChi Code: InChI=1S/C18H21Cl2NO2/c1-18(21,12-22)9-8-13-2-5-15(6-3-13)23-11-14-4-7-16(19)17(20)10-14/h2-7,10,22H,8-9,11-12,21H2,1H3/t18-/m0/s1. InChi Key: ZQQHXJCIFGMUPY-SFHVURJKSA-N.