Datopotamab deruxtecan
[CAS# 2238831-60-0]

Identification

• Classification: Biochemical >> Antibody
• Name: Datopotamab deruxtecan
• Molecular Weight: ~156,000
• CAS Registry Number: 2238831-60-0

Discovory and Applicatios

Datopotamab deruxtecan is an antibody-drug conjugate (ADC) developed for targeted cancer therapy, particularly in tumors expressing the TROP2 (trophoblast cell-surface antigen 2) protein. It combines a monoclonal antibody that specifically binds to TROP2 with a cytotoxic payload, enabling selective delivery of the drug to cancer cells while sparing normal tissues.

The discovery of datopotamab deruxtecan involved the identification of TROP2 as a promising target due to its high expression in several epithelial cancers, including lung, breast, and urothelial carcinomas, and its limited presence on normal tissues. This selectivity supports the rationale for ADC development, aiming to increase anti-tumor efficacy and reduce systemic toxicity.

Datopotamab deruxtecan consists of a humanized anti-TROP2 antibody linked to a potent topoisomerase I inhibitor payload via a cleavable linker. After binding to TROP2 on the tumor cell surface, the ADC is internalized, and the linker is cleaved intracellularly to release the cytotoxic agent. This results in DNA damage and cell death, specifically targeting cancer cells overexpressing TROP2.

The application of datopotamab deruxtecan is primarily in oncology, where it is being evaluated in clinical trials for various solid tumors. Early-phase studies have shown promising anti-tumor activity in non-small cell lung cancer (NSCLC) and triple-negative breast cancer (TNBC), especially in patients with tumors expressing high levels of TROP2. The ADC’s design allows for enhanced potency and bystander killing effects, potentially overcoming tumor heterogeneity and resistance mechanisms.

Datopotamab deruxtecan’s development reflects the broader advancement of ADC technology, which combines the specificity of monoclonal antibodies with the cytotoxic power of chemotherapy agents. Its safety profile generally aligns with other ADCs, with manageable adverse events such as hematologic toxicities and gastrointestinal symptoms observed during clinical evaluation.

Ongoing clinical trials are further assessing the efficacy, safety, and optimal dosing regimens of datopotamab deruxtecan, with the goal of expanding its use across a range of TROP2-expressing cancers. This compound exemplifies the potential of targeted therapies to improve outcomes for patients with difficult-to-treat malignancies through precise molecular targeting and delivery.

Datopotamab deruxtecan represents a significant advancement in precision oncology, offering a novel therapeutic option that harnesses the specificity of antibody targeting and the potency of cytotoxic chemotherapy in a single agent designed to maximize tumor cell killing while minimizing systemic toxicity.