CAS Number319460-85-0
SynonymsN-Methyl-2-({3-[(E)-2-(2-pyridinyl)vinyl]-1H-indazol-6-yl}sulfanyl)benzamide; Inlyta; Axitinib (usan); N-Methyl-2-({3-[(E)-2-(pyridin-2-yl)vinyl]-1H-indazol-6-yl}sulfanyl)benzamide; AG-013736 N-Methyl-2-((3-((1E)-2-(pyridin-2-yl)ethenyl)-1H-indazol-6-yl)sulfanyl)benzamide; Axtinib; AVERMECTINB; Axitinib; N-methyl-2-({3-[(E)-2-(pyridin-2-yl)ethenyl]-1H-indazol-6-yl}sulfanyl)benzamide
Molecular FormulaC22H18O1N4S1
Molecular Weight386.48
Purity98.00%
Density1.4±0.1 g/cm3
Boiling Point668.9±55.0 °C at 760 mmHg
Melting Point213-215ºC
Appearanceoff-white solid
Symbol
Signal WordWarning
| Chemical & Physical Properties | |
|---|---|
| CAS Number | 319460-85-0 |
| Catalog No. | 2A-9056537 |
| Chinese Name | 阿西替尼 |
| Synonyms | N-Methyl-2-({3-[(E)-2-(2-pyridinyl)vinyl]-1H-indazol-6-yl}sulfanyl)benzamide; Inlyta; Axitinib (usan); N-Methyl-2-({3-[(E)-2-(pyridin-2-yl)vinyl]-1H-indazol-6-yl}sulfanyl)benzamide; AG-013736 N-Methyl-2-((3-((1E)-2-(pyridin-2-yl)ethenyl)-1H-indazol-6-yl)sulfanyl)benzamide; Axtinib; AVERMECTINB; Axitinib; N-methyl-2-({3-[(E)-2-(pyridin-2-yl)ethenyl]-1H-indazol-6-yl}sulfanyl)benzamide |
| Molecular Formula | C22H18O1N4S1 |
| Molecular Weight | 386.48 |
| Purity | 98.00 |
| Density | 1.4±0.1 g/cm3 |
| Boiling Point | 668.9±55.0 °C at 760 mmHg |
| Melting Point | 213-215ºC |
| Appearance | off-white solid |
| Water Solubility | Water solubility: insoluble; very slightly soluble |
| Storage Condition | -20°C Freezer |
| Application | Axitinib is a multi-target tyrosine kinase inhibitor with IC50 values for inhibiting VEGFR1, VEGFR2, VEGFR3, and PDGFRβ of 4, 20, 4, and 2 nM respectively. |
| HTC | 2933990090 |
| MDL Number | MFCD09837898 |
| SMILES | CNC(=O)c1ccccc1Sc1ccc2c(C=Cc3ccccn3)n[nH]c2c1 |
| 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+ |
| InChI Key | RITAVMQDGBJQJZ-FMIVXFBMSA-N |
| Hazard Symbols | transportation |
| MSDS | msds/56537_1_319460_85_0.pdf |
| Bioactivity | 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. Related Catalog Signaling Pathways >> Protein Tyrosine Kinase/RTK >> PDGFR Signaling Pathways >> Protein Tyrosine Kinase/RTK >> VEGFR Research Areas >> Cancer Target VEGFR1:0.1 nM (IC50) VEGFR2:0.2 nM (IC50) VEGFR3:0.1 nM (IC50) PDGFRβ:1.6 nM (IC50) In Vitro Axitinib (AG-013736) is a potent and selective inhibitor of VEGFR 1 to 3. In transfected or endogenous RTK-expressing cells, Axitinib potently blocks growth factor-stimulated phosphorylation of VEGFR-2 and VEGFR-3 with average IC50 values of 0.2 and 0.1 to 0.3 nM, respectively. Cellular activity against VEGFR-1 is 1.2 nM (measured in the presence of 2.3% bovine serum albumin), equivalent to an absolute IC50 of ~0.1 nM, based on protein binding of Axitinib. The potency against murine VEGFR-2 (Flk-1) in Flk-1-transfected NIH-3T3 cells is 0.18 nM, similar to that of its human homologue. Axitinib shows ~8- to 25-fold higher IC50 against the closely related type III and V family RTKs, including PDGFR-β (1.6 nM), KIT (1.7 nM), and PDGFR-α (5 nM); nanomolar concentrations of Axitinib blocks PDGF BB-mediated human glioma U87MG cell (PDGFR-β-positive) migration but not proliferation[2]. In Vivo A single oral dose of Axitinib (100 mg/kg) markedly suppresses murine VEGFR-2 phosphorylation for up to 7 h compared with control tumors. Axitinib rapidly inhibits VEGF-induced vascular permeability in the skin of mice; the inhibition is dose-dependent and directly correlated with drug concentration in mice. Pharmacokinetic/pharmacodynamic analysis indicate an unbound EC50 of 0.46 nM. Similar inhibitory effects are also shown in the skin of MV522 tumor-bearing mice without exogenous VEGF-A stimulation. Axitinib inhibits the growth of human xenograft tumors in mice. Axitinib produces dose-dependent growth delay regardless of initial tumor size, model type, or implant site[2]. Cell Assay Endothelial or tumor cells are starved for 18 h in the presence of either 1% FBS (HUVEC) or 0.1% FBS (tumor cells). Axitinib is added and cells are incubated for 45 min at 37°C in the presence of 1 mM Na3VO4. The appropriate growth factor is added to the cells, and after 5 min, cells are rinsed with cold PBS and lysed in the lysis buffer and a protease inhibitor cocktail. The lysates are incubated with immunoprecipitation antibodies for the intended proteins overnight at 4°C. Antibody complexes are conjugated to protein A beads and supernatants are separated by SDS-PAGE[2]. Animal Admin Mice and Rats[2] Mice with M24met xenograft tumors (400-600 mm3) are administered with a single dose of Axitinib or the control (0.5% carboxymethylcellulose/H2O). Blood and tumor tissue samples are collected for pharmacokinetic and VEGFR-2 measurements. Total protein concentrations in tumor tissues are determined using the Bradford colorimetric assay. Six-day-old Sprague-Dawley rats are given two i.p. injections of Axitinib (30 mg/kg ). Animals are sacrificed, retinas are collected and lysed, and immunoprecipitation/immunoblotting experiments are done. ECL-Plus is used for detection and densitometry analysis is done using the Alpha Imager 8800. References [1]. Fenton BM, et al. The addition of AG-013736 to rractionated radiation improves tumor response without functionally normalizing the tumor vasculature. Cancer Res. 2007 Oct 15;67(20):9921-8. [2]. Hu-Lowe DD, et al. Nonclinical antiangiogenesis and antitumor activities of axitinib (AG-013736), an oral, potent, and selective inhibitor of vascular endothelial growth factor receptor tyrosine kinases 1, 2, 3. Clin Cancer Res. 2008 Nov 15;14(22):7272-83 [3]. Allen E, et al. Metabolic Symbiosis Enables Adaptive Resistance to Anti-angiogenic Therapy that Is Dependent on mTOR Signaling. Cell Rep. 2016 May 10;15(6):1144-60. Chemical & Physical Properties Density 1.4±0.1 g/cm3 Boiling Point 668.9±55.0 °C at 760 mmHg Melting Point 213-215ºC Molecular Formula C22H18N4OS Molecular Weight 386.470 Flash Point 358.3±31.5 °C Exact Mass 386.120117 PSA 95.97000 LogP 4.15 Vapour Pressure 0.0±2.0 mmHg at 25°C Index of Refraction 1.728 InChIKey RITAVMQDGBJQJZ-FMIVXFBMSA-N SMILES CNC(=O)c1ccccc1Sc1ccc2c(C=Cc3ccccn3)n[nH]c2c1 Storage condition -20°C Freezer |
| Use of | 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. Properties Name axitinib Synonym More Synonyms Axitinib Biological Activity 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. Related Catalog Signaling Pathways >> Protein Tyrosine Kinase/RTK >> PDGFR Signaling Pathways >> Protein Tyrosine Kinase/RTK >> VEGFR Research Areas >> Cancer VEGFR1:0.1 nM (IC50) VEGFR2:0.2 nM (IC50) VEGFR3:0.1 nM (IC50) PDGFRβ:1.6 nM (IC50) References [1]. Fenton BM, et al. The addition of AG-013736 to rractionated radiation improves tumor response without functionally normalizing the tumor vasculature. Cancer Res. 2007 Oct 15;67(20):9921-8. [3]. Allen E, et al. Metabolic Symbiosis Enables Adaptive Resistance to Anti-angiogenic Therapy that Is Dependent on mTOR Signaling. Cell Rep. 2016 May 10;15(6):1144-60. Chemical & Physical Properties Molecular Formula C22H18N4OS Exact Mass 386.120117 PSA 95.97000 Index of Refraction 1.728 InChIKey RITAVMQDGBJQJZ-FMIVXFBMSA-N |
| Tax Rebate | 13.0% |
| Supervision | None. MFN tariff: 6.5%. Ordinary tariff: 20.0% |
| Transport Info | Shipping Name: UN |
| MSDS Transport Info | Module 14. Shipping information 14.1 UN dangerous goods number European Land Transport Danger Regulations: 3077 International Maritime Transport Danger Regulations: 3077 International Air Transport Danger Regulations: 3077 14.2 United Nations shipping name European land transport hazard regulations: ENVIRONMENTALLY HAZARDOUS SUBSTANCE, SOLID, N.O.S. (Axitinib) IMDG: ENVIRONMENTALLY HAZARDOUS SUBSTANCE, SOLID, N.O.S. (Axitinib) International air transport hazard regulations: Environmentally hazardous substance, solid, n.o.s. (Axitinib) 14.3 Transport hazard categories European land transport Dangerous Regulations: 9 International sea transport Dangerous Regulations: 9 International air transport Dangerous Regulations: 9 14.4 Package group European Land Transport Danger Regulations: III International Maritime Transport Danger Regulations: III International Air Transport Danger Regulations: III 14.5 Environmental hazards European Land Transport Dangerous Regulations: Yes International Maritime Transport Dangerous Regulations International Air Transport Dangerous Regulations: Yes Marine Pollutants (Yes/No): Yes 14.6 Special reminder to users further information Dangerous goods are individually packaged, with liquids exceeding 5 liters or solids exceeding 5 kilograms. The outer packaging of each independent package and the combined independent inner package must have EHS on it. Identification (according to European ADR Regulation 2.2.9.1.10, IMDG Regulation 2.10.3), |
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