Design, synthesis and evaluation of anti-CD38 antibody drug conjugate based on Daratumumab and maytansinoid. Issue 3 (1st February 2019)

• Record Type: Journal Article
• Authors: Zhang, Xinfu; Zhang, Chengxiang; Yang, Xiaomei; Hou, Xucheng; Zhao, Weiyu; Benson, Don; Yu, Jianhua; Dong, Yizhou
• Is Part Of: Bioorganic & medicinal chemistry. Volume 27:Issue 3(2019)
• Page Start: 479
• Page End: 482
• Publication Date: 2019-02-01
• Subjects: CD38 -- Maytansinoid -- Multiple myeloma -- Antibody drug conjugate; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2018.12.024
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: Daratumumab, an FDA approved antibody drug, displays specific targeting ability to abnormal white blood cells overexpressing CD38 and provides efficacious therapy for multiple myeloma. Here, in order to achieve enhanced remission of multiple myeloma, we designedDara-DM4, antibody drug conjugates (ADCs) by conjugating Daratumumab and DM4 via a disulfide linker.Dara-DM4 showed significantly higher cellular uptake and inhibitory efficacy on MM1S cells that overexpressing CD38 with an IC50 of 0.88 µg/mL post 72 hr treatment. These results support a promising ADCs strategy for multiple myeloma treatment.