Synthesis and evaluation of homocamptothecin antibody-drug conjugates for cancer treatment

• Published in: European journal of medicinal chemistry Vol. 279; p. 116899
• Main Authors: Li, Yalong, Cheng, Zhiyang, Zhou, Wei, Wang, Lei, Li, Xiaomei, Xia, Guangxin, Lu, Wei, Zhu, Shulei
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 05.12.2024
• Subjects: Antibody-drug conjugates (ADCs); Cancer treatment; Homocamptothecin; Antibody-drug conjugates (ADCs); Cancer treatment; Homocamptothecin
• ISSN: 0223-5234; 1768-3254; 1768-3254
• DOI: 10.1016/j.ejmech.2024.116899

As an emerging tumor therapeutic strategy, antibody-drug conjugates (ADCs) overcome the high toxicity of traditional small molecule chemotherapy and improve the targeting of treatment. In this study, we successfully constructed a novel ADC, Tras-16b, for the first time using homocamptothecin 16b as the payload. Tras-16b, at a dose of 3 mg/kg, exhibited comparable anti-tumor activity to Enhertu and demonstrated an enhanced safety profile in the NCI–N87 xenograft model. Notably, this is the first ADC developed based on homocamptothecin, marking a significant advancement with promising prospects for the structural modification of camptothecin ADCs. [Display omitted] •Two novel homocamptothecins were designed, synthesized, and evaluated.•Two antibody drug conjugates (ADCs) with homocamptothecins had comparable in vivo anti-tumor efficacy to Enhertu.•This work explored homocamptothecins as payloads of ADCs for the first time.