Basic information FDA approved axitinib use of treating advanced kidney cancer Safety Related Supplier
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Axitinib

Basic information FDA approved axitinib use of treating advanced kidney cancer Safety Related Supplier
Axitinib Basic information
Axitinib Chemical Properties
  • Melting point:213-215°C
  • Boiling point:668.9±55.0 °C(Predicted)
  • Density 1.4
  • storage temp. -20°C Freezer
  • solubility DMSO: ≥8mg/mL
  • form powder
  • pka12.70±0.40(Predicted)
  • color white to tan
  • InChIKeyRITAVMQDGBJQJZ-FMIVXFBMSA-N
  • CAS DataBase Reference319460-85-0(CAS DataBase Reference)
Safety Information
  • Hazard Codes Xn,N
  • Risk Statements 22-50/53
  • Safety Statements 60-61
  • RIDADR UN 3077 9 / PGIII
  • WGK Germany 3
  • HS Code 29333990
Axitinib Usage And Synthesis
  • FDA approved axitinib use of treating advanced kidney cancerJanuary 27, 2012, the FDA approved axitinib for the treatment of advanced kidney cancer (renal cell carcinoma) which other drugs unanswer . Inlyta is manufactured and sold by Pfizer,and is a oral pill taken twice a day.
    Renal cell carcinoma is a type of tumor originating from the tubular endothelial cells. Axitinib can prevent certain protein called kinases playing a role in tumor growth and metastasis .
    Axitinib is a small molecule tyrosine kinase inhibitor, effective against multiple targets, including VEGF receptors 1, 2 and 3.
    Dr. Richard Pazdur, hematology and oncology drugs office director of FDA Drug Evaluation and Research Centre, said: "This is the seven kind of drugs allowed treating metastatic or advanced renal cell carcinoma since 2005 . Overall, during this time ,record level of drug development has dramatically changed the treatment of metastatic renal cell carcinoma paradigm, and offers a variety of treatment options for patients. "
    In recent years, the drug has been approved for the treatment of kidney cancer include sorafenib (2005), sunitinib (2006), temsirolimus(2007), everolimus (2009), bevacizumab(2009) and pazopanib(2009).
    The above information is edited by the chemicalbook of Tian Ye.
  • DescriptionIn January 2012, the US FDA approved axitinib (also referred to as AG-013736) for the treatment of advanced renal cell carcinoma (RCC) for patients who have not responded to prior therapy. Axitinib is a pan VEGF inhibitor and functions by binding to the intracellular tyrosine kinase catalytic domain of VEGF leading to blockade of signaling through this angiogenic pathway. Axitinib is50–400 times more potent for VEGF (enzyme Ki and cellular IC50s for VEGF 1, 2, and 3 are ~0.1 nM) than first-generation inhibitors like sorafenib and sunitinib. Axitinib also inhibits c-Kit and PDGFR(α/β) with enzyme Ki's of ~2 nM and was selective when tested against a broad panel of other protein kinases. Axitinib was discovered by a structure-based drug design approach and binds to the kinase domain of VEGF in a DFG-out conformation. Axitinib blocks VEGF-2 phosphorylation up to 7 h postdose in vivo and inhibits endothelial cell proliferation in xenograft tumors implanted in mice. Synthetic routes to axitinib employing a Migita coupling to form the diaryl sulfide and a Heck reaction to install the 2-styrylpyridine moiety have been reported.
  • Chemical PropertiesOff-White Solid
  • OriginatorPfizer (United States)
  • UsesA tyrosine kinase inhibitor; used in cancer therapy.
  • UsesAxitinib (AG-013736) is a multi-target inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFRβ and c-Kit with IC50 of 0.1 nM, 0.2 nM, 0.1-0.3 nM, 1.6 nM and 1.7 nM, respectively.
  • UsesAxitinib is a multi-target inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFRβ and c-Kit with IC50 of 0.1 nM, 0.2 nM, 0.1-0.3 nM, 1.6 nM and 1.7 nM, respectively.
  • UsesAxitinib is a tyrosine kinase inhibitor. Axitinib is used in cancer therapy.
  • DefinitionChEBI: An indazole substituted at position 3 by a 2-(pyridin-2-yl)vinyl group and at position 6 by a 2-(N-methylaminocarboxy)phenylsulfanyl group. Used for the treatment of advanced renal cell carcinoma after failure of a first line systemic tr atment.
  • brand nameInlyta
  • Clinical UseSold under the brand name Inlyta® by Pfizer, Inc., axitinib was approved by the FDA in January 2012 for the treatment of advanced renal cell carcinoma (RCC), specifically after the failure of other systemic treatments. Axitinib slows cancer cell proliferation by inhibition of the vascular endothelial growth factor (VEGF)/VEGF receptor tyrosine (RTK) signaling pathway. In particular, axitinib is a potent inhibitor of VEGF/RTK 1-3, which selectively slows angiogenesis, vascular permeability, and blood flow in solid tumors.
  • Chemical SynthesisNumerous patents and papers have been disclosed on the synthesis of axitinib, a recently published manuscript details the development of the manufacturing route, and this route is depicted in the scheme. The synthesis began with Migita coupling of commercial iodide 17 with thiophenol 18. Interestingly, this transformation’s efficiency relied upon attention to the number of equivalents of base and an inert atmosphere in the reaction vessel, conditions which minimized catalyst poisoning during the reaction. Without isolation, indazole 19 was iodinated to afford diarylthioether 20 in 85-90% yield over the two steps. Protection of the indazole within 20 as its acetamide preceeded a Heck reaction with 2-vinylpyridine, and then subsequent removal of the indazole protection followed by a series of recrystallizations yielded axitinib (IV) in a combined 62% yield over the final 4 steps.

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