For research use only. Not for therapeutic Use.
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.
| Catalog Number | I002474 |
| CAS Number | 845895-51-4 |
| Synonyms | AP23464; AP-23464; AP 23464;(4-((2-cyclopentyl-9-(3-hydroxyphenethyl)-9H-purin-6-yl)amino)phenyl)dimethylphosphine oxide |
| Molecular Formula | C26H30N5O2P |
| Purity | ≥95% |
| Solubility | Soluble in DMSO, not in water |
| Storage | 0 - 4°Cfor short term (days to weeks), or -20 °C for long term (months). |
| IUPAC Name | 3-[2-[2-cyclopentyl-6-(4-dimethylphosphorylanilino)purin-9-yl]ethyl]phenol |
| 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 |
| SMILES | CP(=O)(C)C1=CC=C(C=C1)NC2=NC(=NC3=C2N=CN3CCC4=CC(=CC=C4)O)C5CCCC5 |
| Reference | </br>1:In vitro and in vivo activity of ATP-based kinase inhibitors AP23464 and AP23848 against activation-loop mutants of Kit. 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.Blood. 2005 Jul 1;106(1):227-34. Epub 2005 Mar 3. PMID: 15746079 Free Article</br>2:Inhibition of wild-type and mutant Bcr-Abl by AP23464, a potent ATP-based oncogenic protein kinase inhibitor: implications for CML. 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.Blood. 2004 Oct 15;104(8):2532-9. Epub 2004 Jul 15. PMID: 15256422 Free Article |
