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AP23464

NMR下載 COA and HPLC MSDS下載
names：
(4-((2-cyclopentyl-9-(3-hydroxyphenethyl)-9H-purin-6-yl)amino)phenyl)dimethylphosphine oxide
CAS號(hào)：
845895-51-4
MDL Number：
MF(分子式)： C26H30N5O2P MW(分子量)： 475.52
EINECS: Reaxys Number:
Pubchem ID: Brand:BIOFOUNT

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中文別名	AP23464
英文別名	AP23464; AP-23464; AP 23464
CAS號(hào)	845895-51-4
Inchi	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)
InchiKey	VVOYROSONSLQQK-UHFFFAOYSA-N
分子式 Formula	C26H30N5O2P
分子量 Molecular Weight	475.52
溶解度Solubility
性狀	Solid powder
儲(chǔ)藏條件 Storage conditions	Dry, dark and store at 0-4℃ for short term (days to weeks) or -20℃ for long term (Store correctly 2-3years).

產(chǎn)品說明	AP23464(CAS:845895-51-4):僅限應(yīng)用于工業(yè)或者科學(xué)研究過程中非醫(yī)療目的，不應(yīng)用于人類或動(dòng)物的臨床診斷以及治過程療，該產(chǎn)品非藥用，非食用。
Introduction	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.
Application1
Application2
Application3

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[1]Maekawa T, Ashihara E, Kimura S. The Bcr-Abl tyrosine kinase inhibitor imatinib and promising new agents against Philadelphia chromosome-positive leukemias. Int J Clin Oncol. 2007 Oct;12(5):327-40. Epub 2007 Oct 22. Review. PubMed PMID: 17929114.

[2]Jakubowska J, Czyz M. [Novel inhibitors of Bcr-Abl]. Postepy Hig Med Dosw (Online). 2006;60:697-706. Review. Polish. PubMed PMID: 17245319.

[3] Kimura S, Ashihara E, Maekawa T. New tyrosine kinase inhibitors in the treatment of chronic myeloid leukemia. Curr Pharm Biotechnol. 2006 Oct;7(5):371-9. Review. PubMed PMID: 17076652.

[4] Gotlib J. KIT mutations in mastocytosis and their potential as therapeutic targets. Immunol Allergy Clin North Am. 2006 Aug;26(3):575-92. Review. PubMed PMID: 16931294.

[5] Azam M, Nardi V, Shakespeare WC, Metcalf CA 3rd, Bohacek RS, Wang Y, Sundaramoorthi R, Sliz P, Veach DR, Bornmann WG, Clarkson B, Dalgarno DC, Sawyer TK, Daley GQ. Activity of dual SRC-ABL inhibitors highlights the role of BCR/ABL kinase dynamics in drug resistance. Proc Natl Acad Sci U S A. 2006 Jun 13;103(24):9244-9. Epub 2006 Jun 5. PubMed PMID: 16754879; PubMed Central PMCID: PMC1482597.

6: Dalgarno D, Stehle T, Narula S, Schelling P, van Schravendijk MR, Adams S, Andrade L, Keats J, Ram M, Jin L, Grossman T, MacNeil I, Metcalf C 3rd, Shakespeare W, Wang Y, Keenan T, Sundaramoorthi R, Bohacek R, Weigele M, Sawyer T. Structural basis of Src tyrosine kinase inhibition with a new class of potent and selective trisubstituted purine-based compounds. Chem Biol Drug Des. 2006 Jan;67(1):46-57. PubMed PMID: 16492148.7: Corbin AS, Demehri S, Griswold IJ, Wang Y, Metcalf CA 3rd, Sundaramoorthi R, Shakespeare WC, Snodgrass J, Wardwell S, Dalgarno D, Iuliucci J, Sawyer TK, Heinrich MC, Druker BJ, Deininger MW. In vitro and in vivo activity of ATP-based kinase inhibitors AP23464 and AP23848 against activation-loop mutants of Kit. Blood. 2005 Jul 1;106(1):227-34. Epub 2005 Mar 3. PubMed PMID: 15746079.8: Brunton VG, Avizienyte E, Fincham VJ, Serrels B, Metcalf CA 3rd, Sawyer TK, Frame MC. Identification of Src-specific phosphorylation site on focal adhesion kinase: dissection of the role of Src SH2 and catalytic 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, Moseson EM, 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 by AP23464, a potent ATP-based oncogenic protein kinase inhibitor: implications for CML. Blood. 2004 Oct 15;104(8):2532-9. Epub 2004 Jul 15. PubMed PMID: 15256422.

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