Phosphoinositide 3-kinases (PI3Ks) are a family of ubiquitously distributed lipid kinases that control a wide variety of intracellular signaling pathways. Over the years, PI3K has emerged as an attractive target for the development of novel pharmaceuticals to treat cancer and various other diseases. In the last five years, four of the PI3K inhibitors viz. Idelalisib, Copanlisib, Duvelisib, and Alpelisib were approved by the FDA for the treatment of different types of cancer and several other PI3K inhibitors are currently under active clinical development. So far clinical candidates are non-selective kinase inhibitors with various off-target liabilities due to cross-reactivities. Hence, there is a need for the discovery of isoform-selective inhibitors with improved efficacy and fewer side-effects. The development of isoform-selective inhibitors is essential to reveal the unique functions of each isoform and its corresponding therapeutic potential. Although the clinical effect and relative benefit of pan and isoformselective inhibition will ultimately be determined, with the development of drug resistance and the demand for next-generation inhibitors, it will continue to be of great significance to understand the potential mechanism of isoform-selectivity. Because of the important role of type I PI3K family members in various pathophysiological processes, isoform-selective PI3K inhibitors may ultimately have considerable efficacy in a wide range of human diseases. This review summarizes the progress of isoformselective PI3K inhibitors in preclinical and early clinical studies for anticancer and other various diseases.

磷酸肌醇3-激酶（PI3Ks）是一类无处不在的脂质激酶，可控制多种细胞内信号通路。多年来，PI3K已成为开发用于治疗癌症和各种其他疾病的新型药物的有吸引力的目标。在过去的五年中，有四种PI3K抑制剂。FDA批准将Idelalisib，Copanlisib，Duvelisib和Alpelisib用于治疗不同类型的癌症，并且目前正在积极开发其他几种PI3K抑制剂。迄今为止，由于交叉反应性，临床候选药物是具有各种脱靶作用的非选择性激酶抑制剂。因此，需要发现具有改善的功效和更少的副作用的同工型选择性抑制剂。开发同工型选择性抑制剂对于揭示每种同工型的独特功能及其相应的治疗潜力至关重要。尽管将最终确定泛和同工型选择性抑制的临床效果和相对利益，但随着耐药性的发展和对下一代抑制剂的需求，了解同工型选择性的潜在机制仍将具有重要意义。由于I型PI3K家族成员在各种病理生理过程中的重要作用，同工型选择性PI3K抑制剂最终可能在多种人类疾病中具有相当大的功效。这篇综述总结了同种型选择性PI3K抑制剂在抗癌和其他各种疾病的临床前和早期临床研究中的进展。尽管将最终确定泛和同工型选择性抑制的临床效果和相对利益，但随着耐药性的发展和对下一代抑制剂的需求，了解同工型选择性的潜在机制仍将具有重要意义。由于I型PI3K家族成员在各种病理生理过程中的重要作用，同工型选择性PI3K抑制剂最终可能在多种人类疾病中具有相当大的功效。这篇综述总结了同种型选择性PI3K抑制剂在抗癌和其他各种疾病的临床前和早期临床研究中的进展。尽管将最终确定泛和同工型选择性抑制的临床效果和相对利益，但随着耐药性的发展和对下一代抑制剂的需求，了解同工型选择性的潜在机制仍将具有重要意义。由于I型PI3K家族成员在各种病理生理过程中的重要作用，同工型选择性PI3K抑制剂最终可能在多种人类疾病中具有相当大的功效。这篇综述总结了同种型选择性PI3K抑制剂在抗癌和其他各种疾病的临床前和早期临床研究中的进展。了解同工型选择性的潜在机理将继续具有重要意义。由于I型PI3K家族成员在各种病理生理过程中的重要作用，同工型选择性PI3K抑制剂最终可能在多种人类疾病中具有相当大的功效。这篇综述总结了同种型选择性PI3K抑制剂在抗癌和其他各种疾病的临床前和早期临床研究中的进展。了解同工型选择性的潜在机理将继续具有重要意义。由于I型PI3K家族成员在各种病理生理过程中的重要作用，同工型选择性PI3K抑制剂最终可能在多种人类疾病中具有相当大的功效。这篇综述总结了同种型选择性PI3K抑制剂在抗癌和其他各种疾病的临床前和早期临床研究中的进展。