269390-77-4 Usage
Description
AAL-993 is a cell-permeable anthranilamide that acts as a potent VEGFR inhibitor, targeting the ATP-binding site of VEGFR in its inactive "DFG-out" conformation. It effectively suppresses tumor growth through its anti-angiogenesis activity in mice and rats in vivo. AAL-993 also inhibits PDGFR-β, cKit, and CSF-1R at higher concentrations and has been shown to inhibit hypoxia-induced HIF-1α expression and transcription activation through ERK inhibition without affecting Akt phosphorylation.
Uses
Used in Oncology:
AAL-993 is used as an anti-cancer agent for its potent inhibition of VEGFR-1, VEGFR-2, and VEGFR-3, which contributes to the suppression of tumor growth and anti-angiogenesis activity. It is particularly effective in targeting various types of cancer by disrupting the blood supply necessary for tumor growth and survival.
Used in Drug Development:
AAL-993 is used as a research tool for studying the role of VEGFR signaling and HIF-1α expression in cancer cell growth and survival. Its dual inhibition of VEGFR signaling and HIF-1α expression makes it a valuable compound for understanding the underlying mechanisms of cancer progression and for developing novel therapeutic strategies.
Used in Pharmaceutical Industry:
AAL-993 is used as a lead compound for the development of new anti-cancer drugs targeting VEGFR and related signaling pathways. Its potent inhibition of VEGFR and selectivity for HIF-1α expression make it a promising candidate for further optimization and development into a therapeutic agent for various types of cancer.
Used in Preclinical Studies:
AAL-993 is used as an experimental compound in preclinical studies to evaluate its efficacy and safety in animal models of cancer. These studies help to determine the optimal dosing, administration, and potential side effects of AAL-993 before it can be considered for clinical trials in humans.
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
Check Digit Verification of cas no
The CAS Registry Mumber 269390-77-4 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 2,6,9,3,9 and 0 respectively; the second part has 2 digits, 7 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 269390-77:
(8*2)+(7*6)+(6*9)+(5*3)+(4*9)+(3*0)+(2*7)+(1*7)=184
184 % 10 = 4
So 269390-77-4 is a valid CAS Registry Number.
269390-77-4Relevant articles and documents
N-aryl(thio)anthranilic acid amide derivatives, their preparation and their use as VEGF receptor tyrosine kinase inhibitors
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, (2008/06/13)
Described are compounds of formula (I), wherein W is O or S; X is NR8; Y is CR9R10-(CH2)n wherein R9 and R10 are independently of each other hydrogen or lower alkyl, and n is an integer of
