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

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

  • Oncotarget. 2016 May 31;7(22):32641-51. doi: 10.18632/oncotarget.8702.
Xiaochuan Liu 1 2,  Aoli Wang 2 3,  Xiaofei Liang 2 4,  Cheng Chen 2 4,  Juanjuan Liu 2 3,  Zheng Zhao 2 4,  Hong Wu 2 3,  Yuanxin Deng 2 3,  Li Wang 2 4,  Beilei Wang 2 4,  Jiaxin Wu 2 3,  Feiyang Liu 2 3,  Stacey M Fernandes 5,  Sophia Adamia 5,  Richard M Stone 5,  Ilene A Galinsky 5,  Jennifer R Brown 5,  James D Griffin 5,  Shanchun Zhang 4 6,  Teckpeng Loh 1,  Xin Zhang 2,  Wenchao Wang 2 4,  Ellen L Weisberg 5,  Jing Liu 2 4,  Qingsong Liu 2 4 7
Affiliations

Affiliations

  • 1 Department of Chemistry, University of Science and Technology of China, Hefei 230036, Anhui, P. R. China.
  • 2 High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei 230031, Anhui, P. R. China.
  • 3 University of Science and Technology of China, Hefei 230036, Anhui, P. R. China.
  • 4 CHMFL-HCMTC Target Therapy Joint Laboratory, Hefei 230031, Anhui, P. R. China.
  • 5 Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
  • 6 Hefei Cosource Medicine Technology Co. LTD., Hefei 230031, Anhui, P.R.China.
  • 7 Hefei Science Center, Chinese Academy of Sciences, Hefei 230031, Anhui, P. R. China.
PMID: 27081697 DOI: 10.18632/oncotarget.8702
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.

Keywords

B-cell malignances; PI3K; PI3Kδ; kinase inhibitors; leukemia.

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