Axitinib

Axitinib
Clinical data
Trade names	Inlyta, Axinix
Other names	AG013736
AHFS/Drugs.com	Monograph
MedlinePlus	a612017
License data	US DailyMed: Axitinib;
Pregnancy; category	AU: D;
Routes of; administration	By mouth
ATC code	L01EK01 (WHO) ;
Legal status
Legal status	AU: S4 (Prescription only); CA: ℞-only; UK: POM (Prescription only); US: ℞-only; EU: Rx-only;
Pharmacokinetic data
Bioavailability	58%
Protein binding	>99%
Metabolism	Liver (mostly CYP3A4/CYP3A5-mediated but with some contributions from CYP1A2, CYP2C19, UGT1A1)
Elimination half-life	2.5-6.1 hours
Excretion	Feces (41%; 12% as unchanged drug), urine (23%)
Identifiers
	IUPAC name N-Methyl-2-[[3-[(E)-2-pyridin-2-ylethenyl]-1H-indazol-6-yl]sulfanyl]benzamide;
CAS Number	319460-85-0 ;
PubChem CID	6450551;
IUPHAR/BPS	5659;
DrugBank	DB06626 ;
ChemSpider	4953153 ;
UNII	C9LVQ0YUXG;
KEGG	D03218 ;
ChEBI	CHEBI:66910 ;
ChEMBL	ChEMBL1289926 ;
PDB ligand	AXI (PDBe, RCSB PDB);
CompTox Dashboard (EPA)	DTXSID3049049 ;
ECHA InfoCard	100.166.384
Chemical and physical data
Formula	C22H18N4OS
Molar mass	386.47 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CNC(=O)c1ccccc1Sc4ccc3c(C=Cc2ccccn2)n[nH]c3c4;
	InChI InChI=1S/C22H18N4OS/c1-23-22(27)18-7-2-3-8-21(18)28-16-10-11-17-19(25-26-20(17)14-16)12-9-15-6-4-5-13-24-15/h2-14H,1H3,(H,23,27)(H,25,26)/b12-9+ ; Key:RITAVMQDGBJQJZ-FMIVXFBMSA-N ;
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Axitinib, sold under the brand name Inlyta, is a small molecule tyrosine kinase inhibitor developed by Pfizer. It has been shown to significantly inhibit growth of breast cancer in animal (xenograft) models^[4] and has shown partial responses in clinical trials with renal cell carcinoma (RCC)^[5] and several other tumour types.^[6]

It was approved to treat renal cell carcinoma by the U.S. Food and Drug Administration after showing a modest increase in progression-free survival,^[7] though there have been reports of fatal adverse effects.^[8]

^ Cite error: The named reference Inlyta FDA label was invoked but never defined (see the help page).
^ "Inlyta EPAR". European Medicines Agency (EMA). 3 September 2012. Retrieved 6 August 2024.
^ ^a ^b ^c ^d ^e "Inlyta (axitinib) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 25 January 2014.
^ Wilmes LJ, Pallavicini MG, Fleming LM, Gibbs J, Wang D, Li KL, et al. (April 2007). "AG-013736, a novel inhibitor of VEGF receptor tyrosine kinases, inhibits breast cancer growth and decreases vascular permeability as detected by dynamic contrast-enhanced magnetic resonance imaging". Magnetic Resonance Imaging. 25 (3): 319–327. doi:10.1016/j.mri.2006.09.041. PMID 17371720.{{cite journal}}: CS1 maint: overridden setting (link)
^ Rini B, Rixe O, Bukowski R, Michaelson MD, Wilding G, Hudes G, et al. (June 2005). "AG-013736, a multi-target tyrosine kinase receptor inhibitor, demonstrates anti-tumor activity in a Phase 2 study of cytokine-refractory, metastatic renal cell cancer (RCC)". Journal of Clinical Oncology ASCO Annual Meeting Proceedings. 23 (16S): 4509. Archived from the original on 26 January 2014.{{cite journal}}: CS1 maint: overridden setting (link)
^ Rugo HS, Herbst RS, Liu G, Park JW, Kies MS, Steinfeldt HM, et al. (August 2005). "Phase I trial of the oral antiangiogenesis agent AG-013736 in patients with advanced solid tumors: pharmacokinetic and clinical results". Journal of Clinical Oncology. 23 (24): 5474–5483. doi:10.1200/JCO.2005.04.192. PMID 16027439.{{cite journal}}: CS1 maint: overridden setting (link)
^ "FDA Approves Inlyta for Advanced Renal Cell Carcinoma". Drugs.com. 27 January 2012.
^ Fauber J, Chu E (27 October 2014). "The Slippery Slope: Is a Surrogate Endpoint Evidence of Efficacy?". MedPage Today.

[Inlyta_FDA_label-1] Cite error: The named reference Inlyta FDA label was invoked but never defined (see the help page).

[Inlyta_EPAR-2] "Inlyta EPAR". European Medicines Agency (EMA). 3 September 2012. Retrieved 6 August 2024.

[MSR-3] "Inlyta (axitinib) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 25 January 2014.

[4] Wilmes LJ, Pallavicini MG, Fleming LM, Gibbs J, Wang D, Li KL, et al. (April 2007). "AG-013736, a novel inhibitor of VEGF receptor tyrosine kinases, inhibits breast cancer growth and decreases vascular permeability as detected by dynamic contrast-enhanced magnetic resonance imaging". Magnetic Resonance Imaging. 25 (3): 319–327. doi:10.1016/j.mri.2006.09.041. PMID 17371720.{{cite journal}}: CS1 maint: overridden setting (link)

[5] Rini B, Rixe O, Bukowski R, Michaelson MD, Wilding G, Hudes G, et al. (June 2005). "AG-013736, a multi-target tyrosine kinase receptor inhibitor, demonstrates anti-tumor activity in a Phase 2 study of cytokine-refractory, metastatic renal cell cancer (RCC)". Journal of Clinical Oncology ASCO Annual Meeting Proceedings. 23 (16S): 4509. Archived from the original on 26 January 2014.{{cite journal}}: CS1 maint: overridden setting (link)

[6] Rugo HS, Herbst RS, Liu G, Park JW, Kies MS, Steinfeldt HM, et al. (August 2005). "Phase I trial of the oral antiangiogenesis agent AG-013736 in patients with advanced solid tumors: pharmacokinetic and clinical results". Journal of Clinical Oncology. 23 (24): 5474–5483. doi:10.1200/JCO.2005.04.192. PMID 16027439.{{cite journal}}: CS1 maint: overridden setting (link)

[FDA3072-7] "FDA Approves Inlyta for Advanced Renal Cell Carcinoma". Drugs.com. 27 January 2012.

[endpoint-8] Fauber J, Chu E (27 October 2014). "The Slippery Slope: Is a Surrogate Endpoint Evidence of Efficacy?". MedPage Today.

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