2-[(6-Amino-9H-purin-9-yl)methyl]-5-methyl-3-(2-methylphenyl)-4(3H)-quinazolinone (IC87114)
selective inhibitor of the p110δ isoform of PI3 kinase

OTAVA Catalogue Number: 7070707046
CAS Registry Number: 371242-69-2
Purity: 95%+ (HPLC)

Ref.: Billottet et al. A selective inhibitor of the p110δ isoform of PI 3-kinase inhibits AML cell proliferation and survival and increases the cytotoxic effects of VP16. Oncogene (2006), 25, 6648-6659

Abstract: Current therapy for acute myeloid leukemia (AML) is suboptimal with a high incidence of relapse. There is strong evidence that constitutive phosphoinositide 3-kinase (PI3K) activity plays a significant role in the pathophysiol. of AML. PI3K products are derived from the activity of a no. of PI3K catalytic isoforms (class I, II and III) but the relative contribution of these enzymes in AML remains unknown. As nonisoform-selective inhibitors of PI3K such as LY294002 may produce unwanted toxicity to normal tissues, the authors have investigated the role of the leukocyte-restricted p110δ PI3K isoform in 14 cases of AML. The isoform p110δ was detected in all cases whereas the expression levels of the other class I PI3Ks varied more widely, and were often undetectable. The p110δ-selective compd. IC87114 inhibited constitutive phosphorylation of the PI3K target Akt/PKB and reduced cell no. to a mean of 66±5% (range 14-88%). In eight cases, the combination of IC87114 and VP16 (a topoisomerase II inhibitor) was synergistic in reducing viable cell no., and was associated with a reduction in constitutive NF-κB activity. IC87114 did not have direct adverse effects or enhance the activity of VP16 on the proliferation and survival of normal hemopoietic progenitors. Overall, our results identify the p110δ isoform as a potential therapeutic target in AML and support a clinical approach to use isoform-selective over broad-spectrum PI3K inhibitors.