LY345899

LY345899 is an inhibitor of methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) and MTHFD2 (IC50s = 96 and 663 nM, respectively). It decreases the NADPH-to-NADP+ (NADPH/NADP+) and reduced glutathione-to-oxidized glutathione (GSH/GSSG) ratios and increases the production of reactive oxygen species (ROS) in HCT116, SW620, and LoVo colorectal cancer cells when used at a concentration of 10 µM. LY345899 is cytotoxic to SW620 and LoVo cells, an effect that can be reversed by the antioxidant N-acetyl-L-cysteine (NAC, Cay-20261). In vivo, LY345899 (10 mg/kg) reduces tumor growth in a patient-derived xenograft (PDX) mouse model of colorectal cancer.Formal Name: N-[4-(3-amino-1,2,5,6,6a,7-hexahydro-1,9-dioxoimidazo[1,5-f]pteridin-8(9H)-yl)benzoyl]-L-glutamic acid. CAS Number: 10538-99-5. Molecular Formula: C20H21N7O7. Formula Weight: 471.4. Purity: >98%. Formulation: (Request formulation change), A solid. Solubility: DMSO: soluble. lambdamax: 293 nm. SMILES: O=C1N2C3=C(NC(N)=NC3=O)NCC2CN1C4=CC=C(C=C4)C(N[C@H](C(O)=O)CCC(O)=O)=O. InChi Code: InChI=1S/C20H21N7O7/c21-19-24-15-14(17(31)25-19)27-11(7-22-15)8-26(20(27)34)10-3-1-9(2-4-10)16(30)23-12(18(32)33)5-6-13(28)29/h1-4,11-12H,5-8H2,(H,23,30)(H,28,29)(H,32,33)(H4,21,22,24,25,31)/t11?,12-/m0/s1. InChi Key: JSNFRYBHBVDHSG-KIYNQFGBSA-N.