title: Discovery of selective phosphatidylinositol 3-kinase inhibitors to treat hematological malignancies.
abstract: The phosphatidylinositol 3-kinase (PI3K) signaling pathway is associated with chemoresistance and poor prognosis of many cancers, including hematological malignancies (HM), such as leukemia, lymphomas, and multiple myeloma (MM). Targeting PI3K is emerging as a promising strategy in the treatment of these blood cancers. Recent approval of idelalisib, a specific inhibitor of PI3Kδ, for the treatment of several types of HM, is likely to attract more interest in search for novel PI3K inhibitors. Here, we discuss classic and cutting-edge techniques and strategies to identify PI3K inhibitors for the treatment of HM. Each technique has its own strengths and limitations, and their combined application will accelerate the drug discovery process with fewer associated costs.
authors: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-psycho-diseases, Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu 215123, China; College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
authors: Jingyu
authors: J
authors: Zhu
authors: College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China. Electronic address: tingjunhou@zju.edu.cn.
authors: Tingjun
authors: T
authors: Hou
authors: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-psycho-diseases, Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu 215123, China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, Jiangsu 215123, China. Electronic address: xinliangmao@suda.edu.cn.
authors: Xinliang
authors: X
authors: Mao
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D055808:Drug Discovery / Q000379:methods*; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D057166:High-Throughput Screening Assays; D006801:Humans; D062105:Molecular Docking Simulation; D058990:Molecular Targeted Therapy; D058539:Phosphatidylinositol 3-Kinase / Q000737:chemistry / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011487:Protein Conformation; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D058539:Phosphatidylinositol 3-Kinase