Axitinib

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Chemical compound

title: "Axitinib" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public tags: ["receptor-tyrosine-kinase-inhibitors", "2-pyridyl-compounds", "alkene-derivatives", "drugs-developed-by-pfizer", "indazoles", "thioethers", "benzamides"] description: "Chemical compound" topic_path: "general/receptor-tyrosine-kinase-inhibitors" source: "https://en.wikipedia.org/wiki/Axitinib" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0

::summary Chemical compound ::

| bioavailability = 58% | protein_bound = 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%)

| IUPAC_name = N-Methyl-2-[[3-[(E)-2-pyridin-2-ylethenyl]-1H-indazol-6-yl]sulfanyl]benzamide | C=22 | H=18 | N=4 | O=1 | S=1 | smiles = CNC(=O)c1ccccc1Sc4ccc3c(C=Cc2ccccn2)n[nH]c3c4 | StdInChI_Ref = | StdInChI = 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+ | StdInChIKey_Ref = | StdInChIKey = RITAVMQDGBJQJZ-FMIVXFBMSA-N

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 and has shown partial responses in clinical trials with renal cell carcinoma (RCC) and several other tumour types.

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, though there have been reports of fatal adverse effects.

Medical uses

Renal cell carcinoma

It has received approval for use as a treatment for renal cell carcinoma from the US Food and Drug Administration (FDA) (January 2012), the European Medicines Agency (EMA) (September 2012), the UK Medicines and Healthcare products Regulatory Agency (MHRA) (September 2012) and the Australian Therapeutic Goods Administration (TGA) (July 2012).

Clinical trials

A Phase II clinical trial showed good response in combination chemotherapy with gemcitabine for advanced pancreatic cancer. However, Pfizer reported on 30 January 2009, that Phase III clinical trials of the drug when used in combination with gemcitabine showed no evidence of improved survival rates over treatments using gemcitabine alone for advanced pancreatic cancer and halted the trial.

In 2010, a Phase III trial for previously treated metastatic renal cell carcinoma (mRCC) showed significantly extended progression-free survival when compared to sorafenib. In December 2011, the Oncologic Drugs Advisory Committee (ODAC) voted unanimously to recommend that US FDA approve axitinib for the second-line treatment of patients with advanced renal cell carcinoma (RCC), based on the results of the Phase III trial comparing axitinib and sorafenib.

It has also been studied in combination with the ALK1 inhibitor dalantercept.

A study published in 2015 showed that axitinib effectively inhibits a mutated gene (BCR-ABL1[T315I]) that is common in chronic myeloid leukemias and adult acute lymphoblastic leukemias which have become resistant to other tyrosine kinase inhibitors like imatinib. This is one of the first examples of a new indication for an existing drug being discovered by screening known drugs using a patient's own cells.

Adverse effects

Diarrhea, hypertension, fatigue, decreased appetite, nausea, dysphonia, hand-foot syndrome, weight decreased, vomiting, asthenia, and constipation are the most common side effects occurring in more than 20% of patients.

Interactions

Coadministration with strong CYP3A4/CYP3A5 inhibitors and inducers should be avoided where possible as they may increase or reduce plasma exposure of axitinib, respectively.

Mechanism of action

Its primary mechanism of action is thought to be vascular endothelial growth factor receptor 1–3, c-KIT and PDGFR inhibition, this, in turn, enables it to inhibit angiogenesis (the formation of new blood vessels by tumours).

It was also proposed that it might act by inducing autophagy, as some other tyrosine kinase inhibitors, like sorafenib.

It has also been shown to bind (in a different conformation from the VEGF binding) to the BCR-ABL fusion protein, specifically inhibiting the drug-resistant T315I mutant isoform.

::data[format=table title="'''The effect of axitinib on tyrosine kinases'''"]

Protein	IC50 (nM)
VEGFR1	0.1
VEGFR2	0.2
VEGFR3	0.1-0.3
PDGFR	1.6
c-KIT	1.7
::

Pharmacokinetics

::data[format=table title="'''Pharmacokinetic parameters of Axitinib'''"]

Bioavailability	Tmax	Cmax	AUC	Vd	Plasma protein binding	Metabolising enzymes	t1/2	Excretion routes
58%	2.5-4.1 hr	27.8 ng/mL	265 ng•h/mL	160 L	99%	Mostly CYP3A4 and CYP3A5. Lesser contributions from CYP1A2, CYP2C19, UGT1A1	2.5-6.1 hr	Faeces (41%), urine (23%)
::

Society and culture

Legal status

In July 2024, the Committee for Medicinal Products for Human Use of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Axitinib Accord, intended for the treatment of adults with renal cell carcinoma. The applicant for this medicinal product is Accord Healthcare S.L.U.

Economics

Pfizer reported revenue of for Inlyta in 2023.

Brand names

In the European Union, it is sold under the brand name Inlyta.

References

(3 September 2012). "Inlyta EPAR".
"Inlyta (axitinib) dosing, indications, interactions, adverse effects, and more". WebMD.
(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.
(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.
(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.
(27 January 2012). "FDA Approves Inlyta for Advanced Renal Cell Carcinoma".
(27 October 2014). "The Slippery Slope: Is a Surrogate Endpoint Evidence of Efficacy?". MedPage Today.
"Inlyta- axitinib tablet, film coated". Pfizer Inc..
(17 December 2013). "Inlyta : EPAR - Product Information". Pfizer Ltd..
(5 December 2013). "Inlyta 1 mg 3mg, 5 mg & 7mg film-coated tablets - Summary of Product Characteristics (SPC)". Pfizer Limited.
(5 July 2013). "PRODUCT INFORMATION INLYTA (axitinib)". Pfizer Australia Pty Ltd..
(June 2008). "Efficacy of gemcitabine plus axitinib compared with gemcitabine alone in patients with advanced pancreatic cancer: an open-label randomised phase II study". Lancet.
(30 January 2009). "Pfizer pancreatic cancer drug fails, trial halted". Reuters.
(19 November 2010). "Pfizer's Phase III Trial in mRCC Turns Up Positive Results".
(7 December 2011). "ODAC Unanimously Supports Axitinib for Renal Cell Carcinoma".
"ALK1/VEGF Combo Active in Advanced RCC. Jan 2017".
(March 2015). "Axitinib effectively inhibits BCR-ABL1(T315I) with a distinct binding conformation". Nature.
(30 January 2012). "FDA Prescribing Information".
(7 February 2024). "FDA Prescribing Information".
(2011). "Axitinib for the management of metastatic renal cell carcinoma". Drugs in R&D.
(January 2014). "Screening of kinase inhibitors targeting BRAF for regulating autophagy based on kinase pathways". Molecular Medicine Reports.
(25 July 2024). "Axitinib Accord EPAR".
(31 December 2023). "Pfizer's year in review".

::callout[type=info title="Wikipedia Source"] This article was imported from Wikipedia and is available under the Creative Commons Attribution-ShareAlike 4.0 License. Content has been adapted to SurfDoc format. Original contributors can be found on the article history page. ::