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Axitinib

Axitinib structure

CAS No:
319460-85-0
Formula:
C22H18N4OS
Chemical Name:
Axitinib
Synonyms:
Benzamide,N-methyl-2-[[3-[(1E)-2-(2-pyridinyl)ethenyl]-1H-indazol-6-yl]thio]-;N-Methyl-2-[[3-[(1E)-2-(2-pyridinyl)ethenyl]-1H-indazol-6-yl]thio]benzamide;AG 013736;Axitinib;Inlyta;790713-39-2
Categories:
Active Pharmaceutical Ingredients > Antineoplastic Agents

Description

Axitinib is a multi-targeted tyrosine kinase inhibitor with IC50s of 0.1, 0.2, 0.1-0.3, 1.6 nM for VEGFR1, VEGFR2, VEGFR3 and PDGFRβ, respectively.

Axitinib is 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 treatment. It has a role as an antineoplastic agent, a tyrosine kinase inhibitor and a vascular endothelial growth factor receptor antagonist. It is a member of indazoles, a member of pyridines, an aryl sulfide and a member of benzamides.|Axitinib is a second generation tyrosine kinase inhibitor that works by selectively inhibiting vascular endothelial growth factor receptors (VEGFR-1, VEGFR-2, VEGFR-3). Through this mechanism of action, axitinib blocks angiogenesis, tumour growth and metastases. It is reported to exhibit potency that is 50-450 times higher than that of the first generation VEGFR inhibitors. Axitinib is an indazole derivative. It is most commonly marketed under the name Inlyta® and is available in oral formulations.|Axitinib is a Kinase Inhibitor. The mechanism of action of axitinib is as a Receptor Tyrosine Kinase Inhibitor.|Axitinib is an oral tyrosine kinase inhibitor selective for vascular endothelial growth factor (VEGF) receptors -1, -2 and -3 that is used in the therapy of advanced renal cell carcinoma. Axitinib therapy is commonly associated with transient elevations in serum aminotransferase that are generally mild and asymptomatic. Axitinib has yet to be linked to instances of clinically apparent acute liver injury.|Axitinib is an orally bioavailable tyrosine kinase inhibitor. Axitinib inhibits the proangiogenic cytokines vascular endothelial growth factor (VEGF) and platelet-derived growth factor receptor (PDGF), thereby exerting an anti-angiogenic effect.|A benzamide and indazole derivative that acts as a TYROSINE KINASE inhibitor of the VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR. It is used in the treatment of advanced RENAL CELL CARCINOMA.

Axitinib Basic Attributes

Molecular Weight：

386.47

Exact Mass：

386.47

EC Number：

1308068-626-2

UNII：

C9LVQ0YUXG

NSC Number：

757441

DSSTox ID：

DTXSID3049049

NCI Thesaurus Code：

C38718

ATC Code：

L01EK01|L01XE17|L - Antineoplastic and immunomodulating agents

HScode：

2933990090

Characteristics

PSA：

XLogP3：

4.2

Appearance：

white to tan

Density：

1.4±0.1 g/cm3

Melting Point：

213-215°C

Boiling Point：

668.9°C at 760 mmHg

Flash Point：

358.3±31.5 °C

Refractive Index：

1.728

Water Solubility：

In aqueous media with a pH between 1.1 to 7.8, axitinib has a solubility of over 0.2 μg/mL.DMSO: ≥8mg/mL

Storage Conditions：

-20°C Freezer

Dissociation Constants：

4.8

Safety Information

Transport codes：

UN 3077 9 / PGIII

wgk germany：

hazard class code：

22-50/53

safety instructions：

60-61

Marks：

Xn,N

Precautionary statement(s)：

P273

Hazard Statements：

H302-H400

GHS Classification：

|Warning|H302 (55.07%): Harmful if swallowed [Warning Acute toxicity, oral]|P201, P202, P260, P264, P270, P273, P281, P301+P312, P308+P313, P314, P330, P391, P405, and P501|Aggregated GHS information provided by 69 companies from 4 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Toxicity

Toxicity Summary：

Some of the more serious toxic effects seen in patients taking axitinib include, but are not limited to, hypertension, thrombotic events, hemorrhage, and GI perforation.

Hepatotoxicity：

In large clinical trials of axitinib, elevations in serum aminotransferase levels were common, occurring in up to 25% of patients. Values greater than 5 times the upper limit of normal (ULN), however, were uncommon, occurring in 1% to 2% of recipients. Furthermore, no instances of clinically apparent liver injury from axitinib were reported in prelicensure studies or during the more wide scale use since its approval. Nevertheless, periodic monitoring of liver tests during axitinib therapy is recommended.

Protein Binding：

Plasma protein binding for axitinib is high at over 99% with most protein binding to albumin followed by α1-acid glycoprotein.

Drug Information

Drug Indication：

Used in kidney cell cancer and investigated for use/treatment in pancreatic and thyroid cancer.|FDA Label|Inlyta is indicated for the treatment of adult patients with advanced renal cell carcinoma (RCC) after failure of prior treatment with sunitinib or a cytokine.|Drug: Axitinib

LiverTox Summary：

Axitinib is an oral tyrosine kinase inhibitor selective for vascular endothelial growth factor (VEGF) receptors -1, -2 and -3 that is used in the therapy of advanced renal cell carcinoma. Axitinib therapy is commonly associated with transient elevations in serum aminotransferase that are generally mild and asymptomatic. Axitinib has yet to be linked to instances of clinically apparent acute liver injury.

Drug Classes：

Antineoplastic Agents

Pharmacology：

Axitinib prevents the progression of cancer by inhibiting angiogenesis and blocking tumor growth.

MeSH：

Substances that inhibit or prevent the proliferation of NEOPLASMS. (See all compounds classified as Antineoplastic Agents.)|Agents that inhibit PROTEIN KINASES. (See all compounds classified as Protein Kinase Inhibitors.)

Absorption：

After one 5 mg dose of axitinib, it takes about 2.5 to 4.1 hours to reach maximum plasma concentration.|Axitinib is mainly eliminated unchanged in the feces (41%) with 12% of the original dose as unchanged axitinib. There is also 23% eliminated in the urine, most of which are metabolites.|The volume of distribution is 160 L.|The average clearance of axitinib is 38 L/h.

Metabolism/Metabolites：

Axitinib undergoes mainly hepatic metabolism. CYP3A4 and CYP3A5 are the main hepatic enzymes while CYP1A2, CYP2C19, and UGT1A1 enzymes are secondary.

Biological Half-Life：

Axitinib has a half life of 2.5 to 6.1 hours.

Mechanism of Action：

Axitinib selectively blocks the tyrosine kinase receptors VEGFR-1 (vascular endothelial growth factor receptor), VEGFR-2, and VEGFR-3.

MeSH Entry Terms：

AG 013736

Axitinib Use and Manufacturing

Uses

Axitinib is a tyrosine kinase inhibitor. Axitinib is used in cancer therapy.

Use Classification：

Human drugs -> Inlyta -> EMA Drug Category|Protein kinase inhibitors -> Human pharmacotherapeutic group|Human drugs -> Rare disease (orphan)|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients

Computed Properties

Molecular Weight:386.5
XLogP3:4.2
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:5
Exact Mass:386.12013238
Monoisotopic Mass:386.12013238
Topological Polar Surface Area:96
Heavy Atom Count:28
Complexity:557
Defined Bond Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes

Drug Function and Efficacy

Targets VEGFR-1, VEGFR-2, VEGFR-3, c-KIT

This ingredient has been used in drugs with the following functions (note: it does not mean that the ingredient itself has the following health functions)

Related Drugs

Axitinib Tablets
Ingredients	Axitinib
Indication	Drug interactions may occur if used with other drugs. Please consult your doctor or pharmacist for details.
Specifications	5 mg x 28 tablets

Axitinib Tablets
Specifications	5mg

Axitinib Tablets
Specifications	1mg

See More Related Drugs

Registered Holders

SHILPA PHARMA LIFESCIENCES LTD

United States
Active
Synthon B.V.

Netherlands
Active
APOTEX INC

Brazil
Active

See More Registered Holders

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