Semaxanib

Semaxanib

Systematic (IUPAC) name
(3Z)-3-[(3,5-dimethyl-1H-pyrrol-2-yl)methylidene]-1,3-dihydro-2H-indol-2-one
Identifiers
CAS Number	194413-58-6
ATC code	none
PubChem	CID 5329098
IUPHAR/BPS	5056
ChemSpider	4486260
UNII	71IA9S35AJ
ChEBI	CHEBI:91083
ChEMBL	CHEMBL276711
Chemical data
Formula	C15H14N2O
Molar mass	238.285 g/mol
SMILES O=C2C(\c1ccccc1N2)=C/c3c(cc(n3)C)C
InChI InChI=1S/C15H14N2O/c1-9-7-10(2)16-14(9)8-12-11-5-3-4-6-13(11)17-15(12)18/h3-8,16H,1-2H3,(H,17,18)/b12-8- Key:WUWDLXZGHZSWQZ-WQLSENKSSA-N
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Semaxanib^[1] (SU5416) is a tyrosine-kinase inhibitor drug designed by SUGEN as a cancer therapeutic. It is an experimental stage drug, not licensed for use on human patients outside of clinical trials. Semaxanib is a potent and selective synthetic inhibitor of the Flk-1/KDR vascular endothelial growth factor (VEGF) receptor tyrosine kinase. It targets the VEGF pathway, and both in vivo and in vitro studies have demonstrated antiangiogenic potential.

On February 2002, Pharmacia, the then-parent of Sugen, prematurely ended Phase III clinical trials of semaxinib in the treatment of advanced colorectal cancer due to discouraging results.^[2] Other studies, at earlier phases, have since been conducted.^[3][4] However, due to the prospect of next-generation tyrosine kinase inhibitors and the ineffaciousness of semaxanib in clinic trials, further development of the drug has been discontinued.^[5] A related compound, SU11248 was further developed by Sugen, and then by Pfizer and was FDA-approved as sunitinib (Sutent) for treatment of renal carcinoma in January 2006.

References

1. World Health Organization (2001). "International Nonproprietary Names for Pharmaceutical Substances (INN). Proposed INN: List 85". WHO Drug Information 15 (2). Full text PDF (244 KiB)
2. "Pharmacia Announces Closing of SU5416 (semaxanib) Clinical Trials" (Press release). February 8, 2002. Retrieved 2007-03-20.
3. O'Donnell A, Padhani A, Hayes C, Kakkar A, Leach M, Trigo J, Scurr M, Raynaud F, Phillips S, Aherne W, Hardcastle A, Workman P, Hannah A, Judson I (2005). "A Phase I study of the angiogenesis inhibitor SU5416 (semaxanib) in solid tumours, incorporating dynamic contrast MR pharmacodynamic end points". Br J Cancer 93 (8): 876–83. doi:10.1038/sj.bjc.6602797. PMC 2361651. PMID 16222321.
4. Lockhart A, Cropp G, Berlin J, Donnelly E, Schumaker R, Schaaf L, Hande K, Fleischer A, Hannah A, Rothenberg M (2006). "Phase I/pilot study of SU5416 (semaxinib) in combination with irinotecan/bolus 5-FU/LV (IFL) in patients with metastatic colorectal cancer". Am J Clin Oncol 29 (2): 109–15. doi:10.1097/01.coc.0000199882.53545.ac. PMID 16601426.
5. Hoff, PM; et al. (2006). "A Phase I Study of Escalating Doses of the Tyrosine Kinase Inhibitor Semaxanib (SU5416) in Combination with Irinotecan in Patients with Advanced Colorectal Carcinoma". Japanese Journal of Clinical Oncology 36 (2): 100–103. doi:10.1093/jjco/hyi229. PMID 16449240.