WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 205994
CAS#: 204005-46-9 (free base)
Description: Semaxanib, also known as SU5416, is a quinolone derivative with potential antineoplastic activity. Semaxanib reversibly inhibits ATP binding to the tyrosine kinase domain of vascular endothelial growth factor receptor 2 (VEGFR2), which may inhibit VEGF-stimulated endothelial cell migration and proliferation and reduce the tumor microvasculature. This agent also inhibits the phosphorylation of the stem cell factor receptor tyrosine kinase c-kit, often expressed in acute myelogenous leukemia cells.
MedKoo Cat#: 205994
CAS#: 204005-46-9 (free base)
Chemical Formula: C15H14N2O
Exact Mass: 238.11061
Molecular Weight: 238.28
Elemental Analysis: C, 75.61; H, 5.92; N, 11.76; O, 6.71
Synonym: SU5416; SU-5416; SU 5416; Sugen 5416; semoxind; Semaxanib
IUPAC/Chemical Name: (Z)-3-((3,5-dimethyl-1H-pyrrol-2-yl)methylene)indolin-2-one
InChi Key: WUWDLXZGHZSWQZ-WQLSENKSSA-N
InChi Code: 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-
SMILES Code: O=C1NC2=C(C=CC=C2)/C1=C/C3=C(C)C=C(C)N3
Semaxanib (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. Other studies, at earlier phases, have since been conducted. 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. 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. (source: http://en.wikipedia.org/wiki/Semaxanib).
1: Yoshizawa Y, Ogawara KI, Fushimi A, Abe S, Ishikawa K, Araki T, Molema G, Kimura T, Higaki K. Deeper Penetration into Tumor Tissues and Enhanced in Vivo Antitumor Activity of Liposomal Paclitaxel by Pretreatment with Angiogenesis Inhibitor SU5416. Mol Pharm. 2012 Nov 14. [Epub ahead of print] PubMed PMID: 23134499.
2: Cui W, Zhang Z, Li W, Mak S, Hu S, Zhang H, Yuan S, Rong J, Choi TC, Lee SM, Han Y. Unexpected neuronal protection of SU5416 against 1-Methyl-4-phenylpyridinium ion-induced toxicity via inhibiting neuronal nitric oxide synthase. PLoS One. 2012;7(9):e46253. doi: 10.1371/journal.pone.0046253. Epub 2012 Sep 25. PubMed PMID: 23049997; PubMed Central PMCID: PMC3457988.
3: Mezrich JD, Nguyen LP, Kennedy G, Nukaya M, Fechner JH, Zhang X, Xing Y, Bradfield CA. SU5416, a VEGF receptor inhibitor and ligand of the AHR, represents a new alternative for immunomodulation. PLoS One. 2012;7(9):e44547. doi: 10.1371/journal.pone.0044547. Epub 2012 Sep 6. PubMed PMID: 22970246; PubMed Central PMCID: PMC3435281.
4: Kim SH, Kang JG, Kim CS, Ihm SH, Choi MG, Yoo HJ, Lee SJ. CCAAT/Enhancer-binding protein-homologous protein sensitizes to SU5416 by modulating p21 and PI3K/Akt signal pathway in FRO anaplastic thyroid carcinoma cells. Horm Metab Res. 2013 Jan;45(1):9-14. doi: 10.1055/s-0032-1323680. Epub 2012 Aug 23. PubMed PMID: 22918703.
5: Lang M, Kojonazarov B, Tian X, Kalymbetov A, Weissmann N, Grimminger F, Kretschmer A, Stasch JP, Seeger W, Ghofrani HA, Schermuly RT. The soluble guanylate cyclase stimulator riociguat ameliorates pulmonary hypertension induced by hypoxia and SU5416 in rats. PLoS One. 2012;7(8):e43433. doi: 10.1371/journal.pone.0043433. Epub 2012 Aug 17. PubMed PMID: 22912874; PubMed Central PMCID: PMC3422306.
6: Mizuno S, Farkas L, Al Husseini A, Farkas D, Gomez-Arroyo J, Kraskauskas D, Nicolls MR, Cool CD, Bogaard HJ, Voelkel NF. Severe pulmonary arterial hypertension induced by SU5416 and ovalbumin immunization. Am J Respir Cell Mol Biol. 2012 Nov;47(5):679-87. doi: 10.1165/rcmb.2012-0077OC. Epub 2012 Jul 27. PubMed PMID: 22842496.
7: Chyou S, Tian S, Ekland EH, Lu TT. Normalization of the lymph node T cell stromal microenvironment in lpr/lpr mice is associated with SU5416-induced reduction in autoantibodies. PLoS One. 2012;7(3):e32828. doi: 10.1371/journal.pone.0032828. Epub 2012 Mar 6. PubMed PMID: 22412930; PubMed Central PMCID: PMC3295768.
8: Ren W, Zhang R, Wu B, Wooley PH, Hawkins M, Markel DC. Effects of SU5416 and a vascular endothelial growth factor neutralizing antibody on wear debris-induced inflammatory osteolysis in a mouse model. J Inflamm Res. 2011;4:29-38. doi: 10.2147/JIR.S16232. Epub 2011 Mar 2. PubMed PMID: 22096367; PubMed Central PMCID: PMC3218747.
9: Keskin U, Totan Y, Karadağ R, Erdurmuş M, Aydın B. Inhibitory effects of SU5416, a selective vascular endothelial growth factor receptor tyrosine kinase inhibitor, on experimental corneal neovascularization. Ophthalmic Res. 2012;47(1):13-8. doi: 10.1159/000324994. Epub 2011 Jun 21. PubMed PMID: 21691137.
10: Mohan N, Karmakar S, Banik NL, Ray SK. SU5416 and EGCG work synergistically and inhibit angiogenic and survival factors and induce cell cycle arrest to promote apoptosis in human malignant neuroblastoma SH-SY5Y and SK-N-BE2 cells. Neurochem Res. 2011 Aug;36(8):1383-96. doi: 10.1007/s11064-011-0463-9. Epub 2011 Apr 7. PubMed PMID: 21472456.