PD 180970

• CAT Number: R062076
• CAS Number: 287204-45-9
• Molecular Formula: C21H15Cl2FN4O
• Molecular Weight: 429.276
• Purity: ≥95%
• Target: Bcr-Abl
• Solubility: Soluble in DMSO > 10 mM
• Storage: Store at +4C
• IUPAC Name: 6-(2,6-dichlorophenyl)-2-(4-fluoro-3-methylanilino)-8-methylpyrido[2,3-d]pyrimidin-7-one
• InChI: InChI=1S/C21H15Cl2FN4O/c1-11-8-13(6-7-17(11)24)26-21-25-10-12-9-14(20(29)28(2)19(12)27-21)18-15(22)4-3-5-16(18)23/h3-10H,1-2H3,(H,25,26,27)
• InChIKey: SLCFEJAMCRLYRG-UHFFFAOYSA-N
• SMILES: CC1=C(C=CC(=C1)NC2=NC=C3C=C(C(=O)N(C3=N2)C)C4=C(C=CC=C4Cl)Cl)F

PD180970 is a novel Bcr-Abl inhbiitor. PD180970 inhibited in vivo tyrosine phosphorylation of p210Bcr-Abl (IC50 = 170 nM) and the p210BcrAbl substrates Gab2 and CrkL (IC50 = 80 nM) in human K562 chronic myelogenous leukemic cells. In vitro, PD180970 potently inhibited autophosphorylation of p210Bcr-Abl (IC50 = 5 nM) and the kinase activity of purified recombinant Abl tyrosine kinase (IC50 = 2.2 nM). Incubation of K562 cells with PD180970 resulted in cell death. PD180970 is among the most potent inhibitors of the p210Bcr-Abl tyrosine kinase, which is present in almost all cases of human chronic myelogenous leukemia. PD180970 is a promising candidate as a novel therapeutic agent for Bcr-Abl-positive leukemia.

Reference

1: Corbin AS, Griswold IJ, La Rosée P, Yee KW, Heinrich MC, Reimer CL, Druker BJ, Deininger MW. Sensitivity of oncogenic KIT mutants to the kinase inhibitors MLN518 and PD180970. Blood. 2004 Dec 1;104(12):3754-7. Epub 2004 Aug 10. PubMed PMID: 15304388.2: La Rosée P, Corbin AS, Stoffregen EP, Deininger MW, Druker BJ. Activity of the Bcr-Abl kinase inhibitor PD180970 against clinically relevant Bcr-Abl isoforms that cause resistance to imatinib mesylate (Gleevec, STI571). Cancer Res. 2002 Dec 15;62(24):7149-53. PubMed PMID: 12499247.3: Huang M, Dorsey JF, Epling-Burnette PK, Nimmanapalli R, Landowski TH, Mora LB, Niu G, Sinibaldi D, Bai F, Kraker A, Yu H, Moscinski L, Wei S, Djeu J, Dalton WS, Bhalla K, Loughran TP, Wu J, Jove R. Inhibition of Bcr-Abl kinase activity by PD180970 blocks constitutive activation of Stat5 and growth of CML cells. Oncogene. 2002 Dec 12;21(57):8804-16. PubMed PMID: 12483533.4: Nimmanapalli R, O/’Bryan E, Huang M, Bali P, Burnette PK, Loughran T, Tepperberg J, Jove R, Bhalla K. Molecular characterization and sensitivity of STI-571 (imatinib mesylate, Gleevec)-resistant, Bcr-Abl-positive, human acute leukemia cells to SRC kinase inhibitor PD180970 and 17-allylamino-17-demethoxygeldanamycin. Cancer Res. 2002 Oct 15;62(20):5761-9. PubMed PMID: 12384536.5: Dorsey JF, Jove R, Kraker AJ, Wu J. The pyrido[2,3-d]pyrimidine derivative PD180970 inhibits p210Bcr-Abl tyrosine kinase and induces apoptosis of K562 leukemic cells. Cancer Res. 2000 Jun 15;60(12):3127-31. PubMed PMID: 10866298.