CD38-DAC

CD38-directed degrader-antibody conjugates (CD38-DACs) represent an innovative class of targeted cancer therapeutics that combine the precision of antibody-based targeting with the catalytic power of targeted protein degradation (TPD). These conjugates consist of a monoclonal antibody targeting CD38—a glycoprotein highly and uniformly expressed on multiple myeloma cells—linked via a cleavable linker to a potent small-molecule protein degrader, typically a cereblon (CRBN) E3 ligase modulator (CELMoD) or molecular glue degrader (MGD) targeting Ikaros (IKZF1) and Aiolos (IKZF3). Upon binding to CD38 on the surface of multiple myeloma cells, the DAC is internalized, and the linker is cleaved to release the degrader payload. The payload then binds to CRBN, redirecting the E3 ligase complex to induce the selective ubiquitination and proteasomal degradation of IKZF1 and IKZF3. This degradation leads to down-regulation of key oncogenic transcription factors and triggers robust apoptosis in myeloma cells. Intriguingly, CD38-DACs exhibit a unique positive feedback loop: the degradation of IKZF1/3 relieves transcriptional repression of the CD38 gene, upregulating CD38 expression on the tumor cell surface, which in turn enhances the binding and internalization of subsequent DAC molecules. CD38-DACs are primarily being developed for the treatment of relapsed or refractory multiple myeloma (RRMM).

Other names

CD38 degrader-antibody conjugateCD-38 degrader-antibody conjugateCD 38 degrader-antibody conjugateCD38-directed DACCD-38-directed DACCD 38-directed DACCD38-targeting DACCD-38-targeting DACCD 38-targeting DACanti-CD38 DACanti-CD-38 DACanti-CD 38 DAC