Datopotamab deruxtecan

Datopotamab deruxtecan (DS-1062) is an antibody-drug conjugate (ADC) that targets tropomyosin 2 (TROP2) on the surface of trophoblast cells. Datopotamab deruxtecan exhibits antitumor activity by specifically binding to TROP2 and internalizing, releasing DXd to inhibit topoisomerase I (IC₅₀ = 0.31 μM), thereby inducing DNA damage and apoptosis. Datopotamab deruxtecan induces significant antibody-dependent cellular cytotoxicity in the presence of peripheral blood lymphocytes and inhibits tumor growth in xenograft models.

CFPAC-1 cells (Trop2-expressing):706 ng/mL, HGSOC cells (TROP2-negative) viability:5.1 µM, TROP2-over expressing HGSOC cells viability:0.49 µM, BxPC-3 cells (Trop2-expressing):74.6 ng/mL

Methods: Add Datopotamab deruxtecan at concentration gradients (0.01, 0.1, 0.5, 5.0, 50 μg/mL) to USC cell lines, incubate for 72 hours, then assess cell viability via flow cytometry.
Results: TROP2-high cells exhibited high sensitivity to Dato-DXd, while TROP2-low cells showed poor sensitivity. [1]

Methods: TROP2-overexpressing USC cells were subcutaneously implanted into SCID mice. After tumor formation, mice were grouped as follows: Datopotamab deruxtecan, control ADC, datopotamab monoclonal antibody, and solvent control. A single intraperitoneal injection (10 mg/kg) was administered on Day 0, followed by 50 days of maintenance.
Results: Compared to the control group, tumor growth was significantly suppressed and overall survival was markedly prolonged in the Datopotamab deruxtecan-treated mice. [1]
Methods: Male cynomolgus monkeys received intravenous Datopotamab deruxtecan at 6 mg/kg. Plasma concentrations of Datopotamab deruxtecan, total antibody, and DXd, along with tumor DXd concentrations, were measured over 21 days post-administration.
Results: High and sustained DXd concentrations were observed in tumors, while plasma levels remained low, indicating efficient drug delivery to tumors. [2]

Human

Immobilized Human TROP2 Protein (His) at 2 μg/mL (30 μL/well) can bind Datopotamab deruxtecan. The EC50 is 0.006524 μg/mL.

Monoclonal

DXd