Dxd Recombinant Mouse Monoclonal Antibody [PSH0-37]

Function

Dxd (Exatecan derivative for ADC) is a potent DNA topoisomerase I inhibitor, with an IC50 of 0.31 μM, used as a conjugated drug of HER2-targeting ADC (DS-8201a). Dxd is cytotoxic to human cancer cell lines of KPL-4, NCI-N87, SK-BR-3, and MDA-MB-468 with IC50s of 1.43 nM-4.07 nM, but the control IgG-ADC (Dxd is the payload) shows no inhibition on the four cell lines (with HER2 expression). DS-8201a (Dxd is the payload) displays significant suppression on the HER2-positive KPL-4, NCI-N87, and SK-BR-3 cell lines, with IC50 values of 26.8, 25.4, and 6.7 ng/mL, respectively, but with no such inhibition on MDA-MB-468. DXd is a part structure of DS-1062a which is a trophoblast cell surface protein 2 (TROP2)-targeting antibody-drug conjugate (ADC) comprised of a humanized anti-TROP2 monoclonal antibody, enzymatically cleavable peptide-linker, and DXd. DXd is an important part structure of DS-7300a, a novel B7-H3-targeting ADC, using DXd-ADC technology, which is composed of a humanized anti-B7-H3 mAb, an enzymatically cleavable tetra-peptide-based linker, and a potent TOP1 inhibitor, DXd.

Background References

1. Ogitani Y, Aida T, Hagihara K, et al. DS-8201a, A Novel HER2-Targeting ADC with a Novel DNA Topoisomerase I Inhibitor, Demonstrates a Promising Antitumor Efficacy with Differentiation from T-DM1Preclinical Efficacy of DS-8201a, a Novel HER2-Targeting ADC[J]. Clinical Cancer Research, 2016, 22(20): 5097-5108.

2. Okajima D, Yasuda S, Yokouchi Y, et al. Preclinical efficacy studies of DS-1062a, a novel TROP2-targeting antibody-drug conjugate with a novel DNA topoisomerase I inhibitor DXd[J]. 2018.

Synonyms

DXD antibody