Semaxanib

Semaxanib
Clinical data
ATC code	none;
Identifiers
	IUPAC name (3Z)-3-[(3,5-dimethyl-1H-pyrrol-2-yl)methylidene]-1,3-dihydro-2H-indol-2-one;
CAS Number	194413-58-6 ;
PubChem CID	5329098;
IUPHAR/BPS	5056;
ChemSpider	4486260 ;
UNII	71IA9S35AJ;
ChEBI	CHEBI:91083 ;
ChEMBL	ChEMBL276711 ;
Chemical and physical data
Formula	C15H14N2O
Molar mass	238.290 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES O=C2C(\c1ccccc1N2)=C/c3c(cc([nH]3)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 ;
	(what is this?) (verify)

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 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 inefficacy 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

World Health Organization (2001). "International Nonproprietary Names for Pharmaceutical Substances (INN). Proposed INN: List 85". WHO Drug Information. 15 (2). "Full text" (PDF). Archived from the original (PDF) on 2007-03-16. (244 KiB)
"Pharmacia Announces Closing of SU5416 (semaxanib) Clinical Trials" (Press release). February 8, 2002. Retrieved 2007-03-20.
O'Donnell A, Padhani A, Hayes C, Kakkar AJ, Leach M, Trigo JM, Scurr M, Raynaud F, Phillips S, Aherne W, Hardcastle A, Workman P, Hannah A, Judson I (October 2005). "A Phase I study of the angiogenesis inhibitor SU5416 (semaxanib) in solid tumours, incorporating dynamic contrast MR pharmacodynamic end points". British Journal of Cancer. 93 (8): 876–83. doi:10.1038/sj.bjc.6602797. PMC 2361651. PMID 16222321.
Lockhart AC, Cropp GF, Berlin JD, Donnelly E, Schumaker RD, Schaaf LJ, Hande KR, Fleischer AC, Hannah AL, Rothenberg ML (April 2006). "Phase I/pilot study of SU5416 (semaxinib) in combination with irinotecan/bolus 5-FU/LV (IFL) in patients with metastatic colorectal cancer". American Journal of Clinical Oncology. 29 (2): 109–15. doi:10.1097/01.coc.0000199882.53545.ac. PMID 16601426.
Hoff PM, Wolff RA, Bogaard K, Waldrum S, Abbruzzese JL (February 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): 100–3. doi:10.1093/jjco/hyi229. PMID 16449240.

This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.

[1] World Health Organization (2001). "International Nonproprietary Names for Pharmaceutical Substances (INN). Proposed INN: List 85". WHO Drug Information. 15 (2). "Full text" (PDF). Archived from the original (PDF) on 2007-03-16. (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 AJ, Leach M, Trigo JM, Scurr M, Raynaud F, Phillips S, Aherne W, Hardcastle A, Workman P, Hannah A, Judson I (October 2005). "A Phase I study of the angiogenesis inhibitor SU5416 (semaxanib) in solid tumours, incorporating dynamic contrast MR pharmacodynamic end points". British Journal of Cancer. 93 (8): 876–83. doi:10.1038/sj.bjc.6602797. PMC 2361651. PMID 16222321.

[4] Lockhart AC, Cropp GF, Berlin JD, Donnelly E, Schumaker RD, Schaaf LJ, Hande KR, Fleischer AC, Hannah AL, Rothenberg ML (April 2006). "Phase I/pilot study of SU5416 (semaxinib) in combination with irinotecan/bolus 5-FU/LV (IFL) in patients with metastatic colorectal cancer". American Journal of Clinical Oncology. 29 (2): 109–15. doi:10.1097/01.coc.0000199882.53545.ac. PMID 16601426.

[5] Hoff PM, Wolff RA, Bogaard K, Waldrum S, Abbruzzese JL (February 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): 100–3. doi:10.1093/jjco/hyi229. PMID 16449240.