AP23464
WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#:406169
CAS#:845895-51-4
Description:AP23464 is a potent adenosine 5'-triphosphate (ATP)-based inhibitor of Src and Abl kinases, displays antiproliferative activity against a human CML cell line and Bcr-Abl-transduced Ba/F3 cells (IC(50) = 14 nM. AP23464 ablates Bcr-Abl tyrosine phosphorylation, blocks cell cycle progression, and promotes apoptosis of Bcr-Abl-expressing cells. Biochemical assays with purified glutathione S transferase (GST)-Abl kinase domain confirmed that AP23464 directly inhibits Abl activity. Importantly, the low nanomolar cellular and biochemical inhibitory properties of AP23464 extend to frequently observed imatinib mesylate-resistant Bcr-Abl mutants, including nucleotide binding P-loop mutants Q252H, Y253F, E255K, C-terminal loop mutant M351T, and activation loop mutant H396P. AP23464 was ineffective against mutant T315I, an imatinib mesylate contact residue. The potency of AP23464 against imatinib mesylate-refractory Bcr-Abl and its distinct binding mode relative to imatinib mesylate warrant further investigation of AP23464 for the treatment of CML.
Price and Availability
AP23464, purity > 98%,is not in stock, may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.
Chemical Structure
Theoretical Analysis
MedKoo Cat#: 406169Name: AP23464CAS#: 845895-51-4Chemical Formula: C26H30N5O2PExact Mass: 475.21371Molecular Weight: 475.52Elemental Analysis: C, 65.67; H, 6.36; N, 14.73; O, 6.73; P, 6.51
Synonym:AP23464; AP-23464; AP 23464
IUPAC/Chemical Name:(4-((2-cyclopentyl-9-(3-hydroxyphenethyl)-9H-purin-6-yl)amino)phenyl)dimethylphosphine oxide
InChi Key:VVOYROSONSLQQK-UHFFFAOYSA-N
InChi Code:InChI=1S/C26H30N5O2P/c1-34(2,33)22-12-10-20(11-13-22)28-25-23-26(30-24(29-25)19-7-3-4-8-19)31(17-27-23)15-14-18-6-5-9-21(32)16-18/h5-6,9-13,16-17,19,32H,3-4,7-8,14-15H2,1-2H3,(H,28,29,30)
SMILES Code:CP(C)(C1=CC=C(NC2=C3N=CN(CCC4=CC=CC(O)=C4)C3=NC(C5CCCC5)=N2)C=C1)=O
Technical Data
Additional Information
References
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8: Brunton VG, Avizienyte E, Fincham VJ, Serrels B, Metcalf CA 3rd,Sawyer TK, Frame MC. Identification of Src-specific phosphorylation siteon focal adhesion kinase: dissection of the role of Src SH2 andcatalytic functions and their consequences for tumor cell behavior.Cancer Res. 2005 Feb 15;65(4):1335-42. PubMed PMID: 15735019.
9: O"Hare T, Pollock R, Stoffregen EP, Keats JA, Abdullah OM, MosesonEM, Rivera VM, Tang H, Metcalf CA 3rd, Bohacek RS, Wang Y,Sundaramoorthi R, Shakespeare WC, Dalgarno D, Clackson T, Sawyer TK,Deininger MW, Druker BJ. Inhibition of wild-type and mutant Bcr-Abl byAP23464, a potent ATP-based oncogenic protein kinase inhibitor:implications for CML. Blood. 2004 Oct 15;104(8):2532-9. Epub 2004 Jul15. PubMed PMID: 15256422.
