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Characterization of selective and potent PI3Kδ inhibitor (PI3KDIN- 015) for B-Cell malignances.
- Source :
-
Oncotarget [Oncotarget] 2016 May 31; Vol. 7 (22), pp. 32641-51. - Publication Year :
- 2016
-
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.<br />Competing Interests: No potential conflicts of interest were disclosed.
- Subjects :
- Amino Acid Sequence
Apoptosis drug effects
Autophagy drug effects
Cell Line, Tumor
Humans
Leukemia, B-Cell enzymology
Leukemia, B-Cell pathology
Models, Molecular
Phosphatidylinositol 3-Kinases chemistry
Enzyme Inhibitors pharmacology
Leukemia, B-Cell drug therapy
Phosphoinositide-3 Kinase Inhibitors
Protein Kinase Inhibitors pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1949-2553
- Volume :
- 7
- Issue :
- 22
- Database :
- MEDLINE
- Journal :
- Oncotarget
- Publication Type :
- Academic Journal
- Accession number :
- 27081697
- Full Text :
- https://doi.org/10.18632/oncotarget.8702