SAF-248, a novel PI3Kδ-selective inhibitor, potently suppresses the growth of diffuse large B-cell lymphoma
| Autor: | Zhou Zuwen, Yi Chen, Dong-Ze Lin, Yu-Ting Duan, Jiang Lihua, Liu Yanxin, Xingdong Zhao, Yu-xiang Wang, Yi Wang, Xi Zhang, Yiming Sun, Jian Ding, Meiyu Geng, Linghua Meng |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cell Survival Class I Phosphatidylinositol 3-Kinases Mice Nude Antineoplastic Agents mTORC1 Article Mice Structure-Activity Relationship 03 medical and health sciences 0302 clinical medicine hemic and lymphatic diseases medicine Animals Humans Pharmacology (medical) Kinome Cells Cultured Cell Proliferation Phosphoinositide-3 Kinase Inhibitors Pharmacology Mice Inbred BALB C Dose-Response Relationship Drug Molecular Structure Kinase Chemistry fungi Neoplasms Experimental General Medicine medicine.disease Lymphoma 030104 developmental biology Apoptosis Cell culture 030220 oncology & carcinogenesis Cancer research Female Lymphoma Large B-Cell Diffuse Drug Screening Assays Antitumor Idelalisib Diffuse large B-cell lymphoma |
| Zdroj: | Acta Pharmacol Sin |
| ISSN: | 1745-7254 1671-4083 |
| DOI: | 10.1038/s41401-021-00644-1 |
| Popis: | PI3Kδ is expressed predominately in leukocytes and overexpressed in B-cell-related malignances. PI3Kδ has been validated as a promising target for cancer therapy, and specific PI3Kδ inhibitors were approved for clinical practice. However, the substantial toxicity and relatively low efficacy as a monotherapy in diffuse large B-cell lymphoma (DLBCL) limit their clinical use. In this study, we described a novel PI3Kδ inhibitor SAF-248, which exhibited high selectivity for PI3Kδ (IC(50) = 30.6 nM) over other PI3K isoforms at both molecular and cellular levels, while sparing most of the other human protein kinases in the kinome profiling. SAF-248 exhibited superior antiproliferative activity against 27 human lymphoma and leukemia cell lines compared with the approved PI3Kδ inhibitor idelalisib. In particular, SAF-248 potently inhibited the proliferation of a panel of seven DLBCL cell lines (with GI(50) values |
| Databáze: | OpenAIRE |
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