Basic information Safety Supplier Related

AAL-993

Basic information Safety Supplier Related

AAL-993 Basic information

Product Name:
AAL-993
Synonyms:
  • AAL-993
  • CS-2315
  • 2-[(4-Pyridinylmethyl)amino]-N-[3-(trifluoromethyl)phenyl]benzami de
  • VEGFR Tyrosine Kinase Inhibitor VI, AAL-993 - CAS 269390-77-4 - Calbiochem
  • 2-(Pyridin-4-ylmethylamino)-N-[3-(trifluoromethyl)phenyl]benzamide
  • Benzamide, 2-[(4-pyridinylmethyl)amino]-N-[3-(trifluoromethyl)phenyl]-
  • antiangiogenic,antitumor properties,AAL 993,VEGFR1,VEGFR2,orally active,VEGFR,AAL993,VEGFR3,Inhibitor,VEGFR inhibitor,AAL-993,Vascular endothelial growth factor receptor,inhibit
CAS:
269390-77-4
MF:
C20H16F3N3O
MW:
371.36
Mol File:
269390-77-4.mol
More
Less

AAL-993 Chemical Properties

Melting point:
158-160 °C
Boiling point:
441.3±45.0 °C(Predicted)
Density 
1.349±0.06 g/cm3(Predicted)
storage temp. 
+2C to +8C
solubility 
Soluble in DMSO (up to 25 mg/ml) or in Ethanol (up to 15 mg/ml).
form 
Off-white powder
pka
12.95±0.70(Predicted)
color 
Pale yellow
Stability:
Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 3 months.
More
Less

AAL-993 Usage And Synthesis

Description

AAL-993 (269390-77-4) inhibits VEGFR-1 (IC50 = 130 nM), VEGFR-2 (IC50 = 23 nM), and VEGFR-3 (IC50 = 18 nM). PDGFR-β, cKit, and CSF-1R are also inhibited at higher concentrations (IC50‘s 640 nM, 236 nM and 380 nM respectively). Screening studies have shown no inhibitory activity against a range of other kinases. X-Ray crystallography has shown that AAL-993 binds to the catalytic domain of VEGFR-2 when the protein is in an inactive conformation. Cell permeable, active in vivo and in whole animal studies.

Uses

AAL-993 is a VEGFR tyrosine kinase inhibitor that possess dual inhibition of VEGFR signaling and HIF-1α expression through ERK inhibition without affecting Akt phosphorylation.

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.

in vitro

aal-993 was found to be a highly potent and selective inhibitor of the recombinant vegfr-2 and vegfr-3 kinases. at 3- to 5-fold higher concentration, aal-993 also inhibited vegfr-1 and, although it possessed some activity against other members of the pdgfr kinase family at submicromolar concentrations, aal-993 did not significantly inhibit any of the other kinases tested at concentrations

in vivo

animal efficacy study found that aal-993 was able to potently inhibit vegf-induced angiogenesis in an implant model, with ed50 values of 7 mg/kg. moreover, in a mouse orthotopic model of melanoma, aal-993 could potently inhibit both the growth of the primary tumor as well as the formation of spontaneous peripheral metastases [1].

IC 50

130, 23, and 18 nm for vegfr1, 2, and 3, respectively

References

1) Manley et al. (2002), Anthranilic acid amides: a novel class of antiangiogenic VEGF receptor kinase inhibitors; J. Med. Chem., 45 5687 2) Manley et al. (2004), Advances in the structural biology, design and clinical development of VEGF-R kinase inhibitors for the treatment of angiogenesis; Biochim. Biophys. Acta, 1697 17

AAL-993Supplier

Shanghai Boyle Chemical Co., Ltd.
Tel
Email
sales@boylechem.com
Sigma-Aldrich
Tel
021-61415566 800-8193336
Email
orderCN@merckgroup.com
Shanghai Lollane Biological Technology Co.,Ltd.
Tel
021-52996696,15000506266 15000506266
Shanghai EFE Biological Technology Co., Ltd.
Tel
021-65675885 18964387627
Email
info@efebio.com
ShangHai Biochempartner Co.,Ltd
Tel
177-54423994 17754423994
Email
2853530910@QQ.com