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| 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]- | | CAS: | 269390-77-4 | | MF: | C20H16F3N3O | | MW: | 371.36 | | EINECS: | | Product Categories: | | Mol File: | 269390-77-4.mol |
| 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. |
| 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-993 Preparation Products And Raw materials |
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