1.A phase I dose escalation and pharmacodynamic study of SU5416 (semaxanib) combined with weekly cisplatin and irinotecan in patients with advanced solid tumors.
Martin LK1, Bekaii-Saab T, Serna D, Monk P, Clinton SK, Grever MR, Kraut EH. Onkologie. 2013;36(11):657-60. doi: 10.1159/000355665. Epub 2013 Oct 14.
BACKGROUND: This phase I study evaluated the safety of SU5416, a potent and selective inhibitor of the vascular endothelial growth factor (VEGF) receptor tyrosine kinase Flk-1, in combination with weekly cisplatin and irinotecan in patients with advanced solid tumors.
2.Photoinduced Isomerization and Hepatoxicities of Semaxanib, Sunitinib and Related 3-Substituted Indolin-2-ones.
Ngai MH1, So CL1, Sullivan MB2, Ho HK1, Chai CL3. ChemMedChem. 2016 Jan 5;11(1):72-80. doi: 10.1002/cmdc.201500475. Epub 2015 Nov 23.
3-Substituted indolin-2-ones are an important class of compounds that display a wide range of biological activities. Sunitinib is an orally available multiple tyrosine kinase inhibitor that has been approved by the US Food and Drug Administration (FDA) for the treatment of renal cell cancer. Sunitinib and a related compound, semaxanib, exist as thermodynamically stable Z isomers, which photoisomerize to E isomers in solution. In this study, 17 3-substituted indolin-2-ones were synthesized, and the kinetics of their photoisomerization were studied by (1)H NMR spectroscopy. The rate constants for photoisomerization ranged from 0.009 to 0.048 h(-1). Selected compounds were tested for cytotoxicity in the TAMH liver cell line. E/Z mixtures of four compounds were also assessed for toxicity in the TAMH and HepG2 cell lines. In some cases, the stereochemically pure drug was more toxic than the E/Z mixtures, but a general statement cannot be made.
