Author correction to “YPD-30, a prodrug of YPD-29B, is an oral small-molecule inhibitor targeting PD-L1 for the treatment of human cancer” [Acta Pharmaceutica Sinica B 12 (2022) 2845–2858]

作者: Jin, Jing ; Dong, Kai ; Chen, Xiaoguang ; Huang, Lei ; Ji, Ming ; Yao, Xiaoqing ; Du, Tingting ; Lai, Fangfang ; Feng, Zhiqiang ; Xue, Nina ; Wang, Yunchen

[This corrects the article DOI: 10.1016/j.apsb.2022.02.031.].

2022-06-01·Acta pharmaceutica Sinica. B

YPD-30, a prodrug of YPD-29B, is an oral small-molecule inhibitor targeting PD-L1 for the treatment of human cancer

Article

作者: Jin, Jing ; Dong, Kai ; Chen, Xiaoguang ; Huang, Lei ; Ji, Ming ; Yao, Xiaoqing ; Feng, Zhiqiang ; Lai, Fangfang ; Du, Tingting ; Xue, Nina ; Wang, Yunchen

PD-1 and PD-L1 antibodies have brought about extraordinary clinical benefits for cancer patients, and their indications are expanding incessantly. Currently, most PD-1/PD-L1 agents are administered intravenously, which may be uncomfortable for some cancer patients. Herein, we develop a novel oral-delivered small molecular, YPD-29B, which specifically targets human PD-L1. Our data suggested that YPD-29B could potently and selectively block the interaction between PD-L1 and PD-1, but did not inhibit any other immune checkpoints. Mechanistically, YPD-29B induced human PD-L1 dimerization and internalization, which subsequently activated T lymphocytes and therefore overcomes immunity tolerance in vitro. YDP-29B was modified as the YPD-30 prodrug to improve druggability. Using humanized mice with human PD-1 xenografts of human PD-L1 knock-in mouse MC38 cancer cells, we demonstrated that YPD-30 exhibited significant antitumor activity and was well tolerated in vivo. Taken together, our results indicate that YPD-30 serves as a promising therapeutic candidate for anti-human PD-L1 cancer immunotherapy.

项与 YPD-30 相关的新闻（医药）

2022-07-06

·生物谷

药学学报！YPD-30是一种针对PD-L1的口服小分子抑制剂，用于治疗人类癌症

癌症免疫治疗是癌症治疗的一个突破，不仅通过延长癌症患者的总体生存时间，而且通过提高生活质量来改变癌症治疗的格局。目前，最成功的免疫疗法包括免疫检查点抑制剂和嵌合抗原受体(CAR)T细胞疗法。癌症免疫治疗是癌症治疗的一个突破，不仅通过延长癌症患者的总体生存时间，而且通过提高生活质量来改变癌症治疗的格局。目前，最成功的免疫疗法包括免疫检查点抑制剂和嵌合抗原受体(CAR)T细胞疗法。抗人类细胞毒性T淋巴细胞抗原4(CTLA4)抗体是第一个被美国食品和药物协会(FDA)正式批准的免疫检查点抑制剂，其次是抗程序性死亡蛋白1(PD-1)/程序性死亡配体1(PD-L1)抗体。由于这些免疫检查点抑制剂的显著疗效已在不同的临床试验中反复报道，这些免疫治疗药物的适应症现已扩大到黑色素瘤、皮肤癌、膀胱癌、头颈癌、肺癌、淋巴瘤、胃癌、胰腺癌和尿路上皮癌。 PD-1和PD-L1抗体为癌症患者带来了非凡的临床益处，其适应证也在不断扩大。目前，大多数PD-1/PD-L1药物都是静脉给药，这可能会让一些癌症患者感到不舒服。图片来源: https://doi-org.libproxy1.nus.edu.sg/10.1016/j.apsb.2022.02.031 近日，来自中国医学科学院和北京协和医学院的研究者们在Acta Pharmaceutica Sinica B杂志上发表了题为“YPD-30, a prodrug of YPD-29B, is an oral small-molecule inhibitor targeting PD-L1 for the treatment of human cancer”的文章，该研究表明YPD-30有望成为抗人PD-L1肿瘤免疫治疗的候选药物。在本研究中，研究者开发了一种新型的口服给药小分子YPD-29B，它专门针对人PD-L1。我们的数据表明YPD-29B可以有效和选择性地阻断PD-L1和PD-1之间的相互作用，但不抑制任何其他免疫检查点。从机制上讲，YPD-29B可诱导人PD-L1的二聚化和内化，进而激活T淋巴细胞，从而克服体外免疫耐受。将YDP-29B修饰为YPD-30前体药，以提高其可药性。用人PD-1基因敲除的小鼠MC38细胞移植人PD-1的人源化小鼠，研究者证明YPD-30具有显著的抗肿瘤活性，在体内耐受性良好。 YPD-29B激活PD-1/NFA T报告基因-Jurkat细胞图片来源: https://doi-org.libproxy1.nus.edu.sg/10.1016/j.apsb.2022.02.031 总之，在本研究中研究者开发了一种针对人PD-L1的有效和选择性的小分子YPD-29B，它可以通过诱导PD-L1二聚化和内化来下调PD-L1的水平，进而激活T淋巴细胞。其前体药物YPD-30具有较强的抗肿瘤活性，在体内耐受性良好，有望作为癌症治疗的药物。（生物谷 Bioon.com）参考文献 Fangfang Lai et al. YPD-30, a prodrug of YPD-29B, is an oral small-molecule inhibitor targeting PD-L1 for the treatment of human cancer. Acta Pharm Sin B. 2022 Jun;12(6):2845-2858. doi: 10.1016/j.apsb.2022.02.031.