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Duocarmycin-based antibody–drug conjugates as an emerging biotherapeutic entity for targeted cancer therapy: Pharmaceutical strategy and clinical progress.
- Source :
-
Drug Discovery Today . Aug2021, Vol. 26 Issue 8, p1857-1874. 18p. - Publication Year :
- 2021
-
Abstract
- • Duocarmycins and analogues are DNA-alkylators highly cytotoxic to cancer cells. • Up to now, none of duocarmycins have not been approved for oncological practice. • Novel features make duocarmycins an ideal payload for targeted drug delivery. • Various duocarmycin-based antibody-drug conjugates are in clinical development. • An emerging era of duocarmycin-based anticancer biotherapeutics is in the horizon. Duocarmycins are a class of DNA minor-groove-binding alkylating molecules. For the past decade, various duocarmycin analogues have been used as payloads in the development of antibody–drug conjugates (ADCs). Currently, more than 15 duocarmycin-based ADCs have been studied preclinically, and some of them such as SYD985 have been granted Fast-Track Designation status. Nevertheless, progress in duocarmycin-based ADCs also faces challenges, with setbacks including the termination of BMS-936561/MDX-1203. In this review, we discuss issues associated with the efficacy, pharmacokinetic profile, and toxicological activity of these biotherapeutics. Furthermore, we summarize the latest advances in duocarmycin-based ADCs that have different target specificities and linker chemistries. Evidence from preclinical and clinical studies has indicated that duocarmycin-based ADCs are promising biotherapeutics for oncological application in the future. [ABSTRACT FROM AUTHOR]
- Subjects :
- *ANTIBODY-drug conjugates
*TARGETED drug delivery
*CANCER treatment
Subjects
Details
- Language :
- English
- ISSN :
- 13596446
- Volume :
- 26
- Issue :
- 8
- Database :
- Academic Search Index
- Journal :
- Drug Discovery Today
- Publication Type :
- Academic Journal
- Accession number :
- 152163359
- Full Text :
- https://doi.org/10.1016/j.drudis.2021.06.012