Characterization of selective and potent PI3Kδ inhibitor (PI3KDIN- 015) for B-Cell malignances.

Related Articles

Characterization of selective and potent PI3Kδ inhibitor (PI3KDIN- 015) for B-Cell malignances.

Oncotarget. 2016 May 31;7(22):32641-51

Authors: Liu X, Wang A, Liang X, Chen C, Liu J, Zhao Z, Wu H, Deng Y, Wang L, Wang B, Wu J, Liu F, Fernandes SM, Adamia S, Stone RM, Galinsky IA, Brown JR, Griffin JD, Zhang S, Loh T, Zhang X, Wang W, Weisberg EL, Liu J, Liu Q

Abstract
PI3Kδ is predominately expressed in leukocytes and has been found overexpressed in B-cell related malignances such as CLL and AML. We have discovered a highly selective ATP competitive PI3Kd inhibitor PI3KD-IN-015, which exhibits a high selectivity among other PI3K isoforms in both biochemical assays and cellular assay, meanwhile did not inhibit most of other protein kinases in the kinome. PI3KD-IN-015 demonstrates moderately anti-proliferation efficacies against a variety of B-cell related cancer cell lines through down-regulate the PI3K signaling significantly. It induced both apoptosis and autophagy in B-cell malignant cell lines. In addition, combination of autophagy inhibitor Bafilomycin could potentiate the moderate anti-proliferation effect of PI3KD-IN-015. PI3KD-IN-015 shows anti-proliferation efficacy against CLL and AML patient primary cells. Collectively, these results indicate that PI3KD-IN-015 may be useful drug candidate for further development of anti-B-cell related malignances therapies.

PMID: 27081697 [PubMed - indexed for MEDLINE]

http://ift.tt/2ncBpu7