Proteins of B-cell lymphoma (Bcl-2) family are key regulators of apoptosis and are involved in the pathogenesis of various cancers. Disrupting the interactions between the antiapoptotic and proapoptotic Bcl-2 members is an attractive strategy to reactivate the apoptosis of cancer cells. Structure-based drug design (SBDD) has been successfully applied to the discovery of small molecule inhibitors targeting Bcl-2 proteins in past decades. Up to now, many Bcl-2 inhibitors with different paralogue selectivity profiles have been developed and some were used in clinical trials. This review focused on the recent applications of SBDD strategies in the development of small molecule inhibitors targeting Bcl-2 family proteins.

B细胞淋巴瘤（Bcl-2）家族的蛋白是细胞凋亡的关键调节因子，并参与各种癌症的发病机制。破坏抗凋亡和促凋亡Bcl-2成员之间的相互作用是重新激活癌细胞凋亡的有吸引力的策略。在过去的几十年中，基于结构的药物设计（SBDD）已成功应用于发现针对Bcl-2蛋白的小分子抑制剂。迄今为止，已经开发了许多具有不同旁系选择性的Bcl-2抑制剂，其中一些已用于临床试验。这篇综述集中在SBDD策略在靶向Bcl-2家族蛋白的小分子抑制剂的开发中的最新应用。