Axitinib
[CAS# 319460-85-0]

Identification

• Classification: API >> Antineoplastic agents >> Tinic antineoplastic agents
• Name: Axitinib
• Synonyms: N-Methyl-2-((3-((1E)-2-(pyridin-2-yl)ethenyl)-1H-indazol-6-yl)sulfanyl)benzamide
• Molecular Formula: C₂₂H₁₈N₄OS
• Molecular Weight: 386.47
• CAS Registry Number: 319460-85-0
• EC Number: 638-771-6
• SMILES: CNC(=O)C1=CC=CC=C1SC2=CC3=C(C=C2)C(=NN3)/C=C/C4=CC=CC=N4

Properties

• Solubility: 25 mM (DMSO)

Safety Data

• Hazard Symbols: GHS07;GHS08;GHS09 Warning
• Risk Statements: H302-H341-H361-H373-H400
• Safety Statements: P203-P260-P264-P270-P273-P280-P301+P317-P318-P319-P330-P391-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute hazardous to the aquatic environment	Aquatic Acute	1	H400
Acute toxicity	Acute Tox.	4	H302
Specific target organ toxicity - repeated exposure	STOT RE	2	H373
Reproductive toxicity	Repr.	2	H361
Germ cell mutagenicity	Muta.	2	H341
Chronic hazardous to the aquatic environment	Aquatic Chronic	1	H410
Reproductive toxicity	Repr.	1B	H360FD
Specific target organ toxicity - single exposure	STOT SE	3	H335
Reproductive toxicity	Repr.	2	H361fd

Discovery and Applications

Axitinib is a small molecule tyrosine kinase inhibitor that has been widely studied for its therapeutic potential in cancer treatment, particularly in the inhibition of angiogenesis. Angiogenesis, the formation of new blood vessels, is a key process in tumor growth, and targeting this pathway has become an effective strategy in cancer therapy. Axitinib specifically inhibits vascular endothelial growth factor receptors (VEGFRs), which are critical for angiogenesis. The compound binds to the ATP-binding site of the VEGFRs, preventing the downstream signaling that promotes the proliferation and survival of endothelial cells.

The discovery of axitinib can be traced to research focused on the development of selective inhibitors for tyrosine kinases. Tyrosine kinase inhibitors have long been a target in the search for cancer therapies, given their role in various cellular signaling pathways that contribute to cancer progression. Through structure-based drug design and optimization, axitinib was developed as a potent and selective VEGFR inhibitor, with additional inhibitory effects on platelet-derived growth factor receptors (PDGFR) and c-Kit. These characteristics make axitinib a multi-targeted therapy that affects various signaling pathways involved in tumor angiogenesis and growth.

One of the main applications of axitinib is in the treatment of advanced renal cell carcinoma (RCC). After demonstrating significant efficacy in clinical trials, axitinib was approved for the treatment of RCC, particularly in patients who have not responded to prior therapies. Its ability to inhibit tumor growth by cutting off the blood supply makes it an important option in cancer treatment. Beyond RCC, axitinib is also being explored in combination therapies for other cancers, including thyroid cancer, hepatocellular carcinoma, and non-small cell lung cancer, where anti-angiogenic strategies are relevant.

In clinical practice, axitinib is typically administered orally, and its pharmacokinetics are characterized by a rapid absorption and metabolism primarily in the liver. Despite its efficacy, axitinib can cause side effects, including hypertension, fatigue, and gastrointestinal disturbances, which are common in therapies targeting angiogenesis. Continued research aims to optimize the use of axitinib in various cancers, as well as explore its combination with other targeted therapies or immunotherapies to enhance overall treatment outcomes.

References

2024. Clinical Relevance and Mechanistic Underpinnings of Tyrosine Kinase Inhibitor Associated Cardiotoxicities. Current Treatment Options in Cardiovascular Medicine, 26(12).
DOI: 10.1007/s11936-024-01067-x

2018. Therapeutic advances in anaplastic thyroid cancer: a current perspective. Molecular Cancer, 17(1).
DOI: 10.1186/s12943-018-0903-0

2017. The opening/closure of the P-loop and hinge of BCR-ABL1 decodes the low/high bioactivities of dasatinib and axitinib. Physical Chemistry Chemical Physics, 19(36).
DOI: 10.1039/c7cp03443a