APS6-45

APS6-45 is an inhibitor of RETM918T and a derivative of sorafenib (Cay-10009644, Cay-35612). It selectively binds to RETM918T over Eph tyrosine kinase receptor A8 (EphA8), p38delta, JNK2, and c-Src (Kds = 28, 410, 940, 1,500, and 1,700 nM, respectively), as well as a panel of over 60 kinases at 10 µM, but also binds to cyclin-dependent kinase 14 (Cdk14), MAP4K4, and protein tyrosine kinase 5 (PTK5, Kds = 55, 130, and 140 nM, respectively). It inhibits TT medullary thyroid carcinoma cell colony formation when used at a concentration of 30 nM. APS6-45 (10 mg/kg per day) decreases tumor volume in a TT mouse xenograft model. It increases survival to adulthood in Drosophila expressing the lethal RetM955T mutation in a concentration-dependent manner. APS6-45 (100 µM) prevents the development of a rough-eye phenotype induced by RetM955T in Drosophila.Formal Name: 4-[4-[[[[2-fluoro-5-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]phenyl]amino]carbonyl]amino]phenoxy]-N-methyl-2-pyridinecarboxamide. CAS Number: 2188236-41-9. Molecular Formula: C23H16F8N4O3. Formula Weight: 548.4. Purity: >98%. Formulation: (Request formulation change), A solid. Solubility: DMF: 5 mg/ml, DMSO: 10 mg/ml, Ethanol: 10 mg/ml. lambdamax: 260 nm. SMILES: O=C(NC1=CC(C(C(F)(F)F)(C(F)(F)F)F)=CC=C1F)NC2=CC=C(C=C2)OC3=CC=NC(C(NC)=O)=C3. InChi Code: InChI=1S/C23H16F8N4O3/c1-32-19(36)18-11-15(8-9-33-18)38-14-5-3-13(4-6-14)34-20(37)35-17-10-12(2-7-16(17)24)21(25,22(26,27)28)23(29,30)31/h2-11H,1H3,(H,32,36)(H2,34,35,37). InChi Key: MVUPJRHPAMCBQJ-UHFFFAOYSA-N.