AC4847-trastuzumab dac

AC4847-trastuzumab dac is a first-in-class degrader-antibody conjugate (DAC) developed by Accutar Biotechnology for the treatment of HER2-overexpressing and PI3Kα-driven cancers, such as breast cancer. It consists of the HER2-targeted monoclonal antibody trastuzumab conjugated to AC4847, a highly potent and selective chimeric PI3Kα degrader payload, via an optimized cleavable linker. AC4847 recruits the Cereblon (CRBN) E3 ligase to induce rapid, proteasome-dependent degradation of PI3Kα, leading to the suppression of downstream pAKT signaling. By delivering the degrader payload selectively to HER2-expressing tumor cells, the DAC achieves robust anti-tumor efficacy and durable tumor regression in preclinical models. Crucially, this targeted delivery avoids the systemic wild-type PI3Kα inhibition that causes dose-limiting metabolic toxicities, such as hyperglycemia and insulin resistance, which are commonly associated with traditional small-molecule PI3Kα inhibitors.

Other names

HER2-PI3Kα DACtrastuzumab-AC4847trastuzumab-AC-4847trastuzumab-AC 4847trastuzumab-PI3Kα DACtrastuzumab-conjugated PI3Kα DAC