676504

VEGFR Tyrosine Kinase Inhibitor VI, AAL-993

The VEGFR Tyrosine Kinse Inhibitor VI, ALL-993, also referenced under CAS 269390-77-4, controls the biological activity of VEGFR Tyrosine Kinase. This small molecule/inhibitor is primarily used for Cancer applications.

• Synonym(s): VEGFR Tyrosine Kinase Inhibitor VI, AAL-993, 2-((4-Pyridyl)methyl)amino-N-(3-(trifluoromethyl)phenyl)benzamide, ZK260253, PDGFR Tyrosine Kinase Inhibitor XXIII, VEGFR2 Kinase Inhibitor XXXIII, VEGFR1 Kinase Inhibitor VIII, VEGFR3 Kinase Inhibitor VII, AAL993, PDGFR Tyrosine Kinase Inhibitor XXIII, 2-((4-Pyridyl)methyl)amino-N-(3-(trifluoromethyl)phenyl)benzamide, ZK260253, VEGFR2 Kinase Inhibitor XXXIII, VEGFR1 Kinase Inhibitor VIII, VEGFR3 Kinase Inhibitor VII, AAL993
• Empirical Formula (Hill Notation): C₂₀H₁₆F₃N₃O
• CAS Number: 269390-77-4
• Molecular Weight: 371.36
• UNSPSC Code: 12352200
• NACRES: NA.28

Properties

• Quality Level: 100
• assay: ≥97% (HPLC)
• form: powder
• manufacturer/tradename: Calbiochem^®
• storage condition: OK to freeze; protect from light
• color: off-white
• solubility: DMSO: 100 mg/mL
• shipped in: ambient
• storage temp.: 2-8°C
• InChI: 1S/C20H16F3N3O/c21-20(22,23)15-4-3-5-16(12-15)26-19(27)17-6-1-2-7-18(17)25-13-14-8-10-24-11-9-14/h1-12,25H,13H2,(H,26,27)
• InChI key: BLAFVGLBBOPRLP-UHFFFAOYSA-N

Description

General description

A cell-permeable anthranilamide that acts as a potent VEGFR inhibitor (IC₅₀ = 130, 23, and 18 nM against VEGFR-1, -2, and -3, respectively; IC₅₀ = 1.24 nM against VEGF-induced human VEGFR-2 phosphorylation in CHO cells) by targeting the ATP-binding site of VEGFR in its inactive "DFG-out" conformation and effectively suppresses tumor growths (50 to 100 mg/kg; p.o.) via its anti-angiogenesis activity in mice and rats in vivo, while inhibiting c-kit, CSF-1R/c-Fms, PDGFR-β, and c-Abl only at higher concentrations (IC₅₀ = 236, 380, 640, and 2820 nM, respectively). AAL933 and two other VEGFR inhibitors, KRN633 and SU5416, are also shown to inhibit hypoxia-induced HIF-1α expression (by <90% at 30 M) and transcription activation. Unlike KRN633 and SU5416, AAL933 prevents only hypoxia-induced Erk, but not Akt, phosphorylation in HeLa cells.

A cell-permeable anthranilamide that acts as a potent VEGFR inhibitor (IC₅₀ = 130, 23, and 18 nM against VEGFR-1, -2, and -3, respectively; IC₅₀ = 1.24 nM against VEGF-induced human VEGFR-2 phosphorylation in CHO cells) by targeting the ATP-binding site of VEGFR in its inactive "DFG-out" conformation, while inhibiting c-kit, CSF-1R/c-Fms, PDGFR-β, and c-Abl only at higher concentrations (IC₅₀ = 236, 380, 640, and 2820 nM, respectively) and displaying little or no activity against EGFR/HER-1/ErbB (IC₅₀ = 10.4 M) and six other kinases (IC₅₀ ≥10 M). Reported to be orally available in mice (Conc. in plasma = 9.5, 4.7, 1.5, and 1.1 M, respectively, 0.5 h, 1 h, 1.5 h, and 2 h after p.o. dosage of 50 mg/kg), rats, and dogs, and effectively suppress tumor growths (50 to 100 mg/kg; p.o.) via its anti-angiogenesis activity in various cancer models in vivo, including murine melanoma B16-BL6, rat mammary adenocarcinoma BN472, as well as human prostate cancer DU145-grafted mice in vivo. AAL933 and two other VEGFR inhibitors, KRN633 and SU5416, are also shown to inhibit hypoxia- (1% O₂) induced HIF-1α expression (by <90% at 30 M) and transcription activation (IC₅₀ = 6.53, 3.79, and 8.24 M, respectively, by AAL933, KRN633, and SU5416 in HeLa-HRE-Luc reporter assays). However, unlike KRN633 and SU5416, AAL933 prevents only hypoxia-induced Erk, but not Akt, phosphorylation in HeLa cells.

Packaging

Packaged under inert gas

Warning

Toxicity: Regulatory Review (Z)

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Other Notes

Ban, H.S., et al. 2010. Cancer Lett.296, 17; Manley, P.W., et al. 2004. Biochim. Biophys. Acta1697, 17; Manley, P.W., et al. 2002. J. Med. Chem.45, 5687.

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Safety Information

• Storage Class: 11 - Combustible Solids
• wgk_germany: WGK 2
• flash_point_f: Not applicable
• flash_point_c: Not applicable