Synthesis and evaluation of homocamptothecin antibody-drug conjugates for cancer treatment
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...
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Published in | European journal of medicinal chemistry Vol. 279; p. 116899 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
France
Elsevier Masson SAS
05.12.2024
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Subjects | |
Online Access | Get full text |
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Summary: | 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.
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•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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0223-5234 1768-3254 1768-3254 |
DOI: | 10.1016/j.ejmech.2024.116899 |