A8370-100mg | Axitinib (AG 013736) [319460-85-0] Clinisciences

Background

Axitinib is a selective and oral inhibitor of vascular endothelial growth factor (VEGF) receptor tyrosine kinases 1, 2 and 3 with [1].

Axitinib inhibited the phosphorylation of VEGFR-1, 2 and 3 with IC50 values of 1.2 nM, 0.2 nM and 0.1 to 0.3 nM in cells, respectively. In HUVEC cells, Axitinib inhibited VEGFR-2 stimulated cell survival with about 1000-fold selectivity against FGFR-1. Axitinib also significantly suppressed the phosphorylation of VEGF downstream signaling molecules including Akt, eNOS and ERK1/2. Besides that, axitinib inhibited VEGFR-2 phosphorylation with EC50 value of 0.49 nM in vivo. It delayed tumore growth of human xenograft tumors in mice such as M24met, HCT-116 and SN12C [1].

References:
[1] Hu-Lowe D D, Zou H Y, Grazzini M L, 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. Clinical Cancer Research, 2008, 14(22): 7272-7283.

Product Citation

1. Schwartz, Hannah, et al. "In vitro Methods to Better Evaluate Drug Responses in Cancer." UMass Chan Medical School. September 8, 2022.
2. Paik ES, Kim TH, et al. "Preclinical assessment of the VEGFR inhibitor axitinib as a therapeutic agent for epithelial ovarian cancer." Sci Rep. 2020;10(1):4904. > PMID: 32184452
3. Anna V. Ivanina, Ballav Borah, et al. "The Role of the Vascular Endothelial Growth Factor (VEGF) Signaling in Biomineralization of the Oyster Crassostrea gigas." Front. Mar. Sci., 28 August 2018.

Chemical Properties

Storage	Store at -20°C
M.Wt	386.47
Cas No.	319460-85-0
Formula	C₂₂H₁₈N₄OS
Synonyms	AG 013736
Solubility	insoluble in H2O; ≥19.3 mg/mL in DMSO; ≥3.52 mg/mL in EtOH
Chemical Name	N-methyl-2-[[3-[(E)-2-pyridin-2-ylethenyl]-1H-indazol-6-yl]sulfanyl]benzamide
SDF	Download SDF
Canonical SMILES	CNC(=O)C1=CC=CC=C1SC2=CC3=C(C=C2)C(=NN3)C=CC4=CC=CC=N4
Shipping Condition	Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice.
General tips	We do not recommend long-term storage for the solution, please use it up soon.

Protocol

Cell experiment [1]:
Cell lines	PAE cells overexpressing RTK, Human umbilical vein endothelial cells (HUVEC)
Preparation method	The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.
Reaction Conditions	Cellular receptor kinase phosphorylation assay: 45 min at 37 ℃ in the presence of 1 mmol/L Na3VO4
Applications	In transfected or endogenous RTK-expressing cells, axitinib potently blocked growth factor-stimulated phosphorylation of VEGFR-2 and VEGFR-3 with average IC50 values of 0.2 and 0.1 to 0.3 nmol/L, respectively. Axitinib inhibited VEGF-stimulated survival of HUVEC with IC50 value of 0.17 nmol/L.
Animal experiment [2]:
Animal models	Female nu/nu mice or severe combined immunodeficient beige mice(ages 7-10 weeks)
Dosage form	Axitinib was dosed as a suspension at 5 mL/kg orally twice daily
Applications	Axitinib dose-dependently inhibits tumor growth in MV522 with ED50 value of 8.8 mg/kg twice daily, based on the relationship between dose and the corresponding TGI (tumor growth inhibition).
Other notes	Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
References: [1]. Hu-Lowe D D, Zou H Y, Grazzini M L, 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. Clinical Cancer Research, 2008, 14(22): 7272-7283.

Biological Activity

Description	Axitinib is a multi-target inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFRβ and c-Kit with IC50 values of 0.1 nM, 0.2 nM, 0.1-0.3 nM, 1.6 nM and 1.7 nM, respectively.
Targets	VEGFR1/FLT1	VEGFR2/Flk1	VEGFR2/KDR	VEGFR3	PDGFRβ	c-Kit
IC50	0.1 nM	0.18 nM	0.2 nM	0.1 nM-0.3 nM	1.6 nM	1.7 nM

Quality Control

Purity = 99.65%

Axitinib (AG 013736) [319460-85-0]

Référence A8370-100mg

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