S227928

S227928 is a novel antibody-drug conjugate (ADC) designed for the treatment of hematologic malignancies, particularly acute myeloid leukemia (AML), chronic myelomonocytic leukemia (CMML), and myelodysplastic syndromes (MDS). The drug consists of an anti-CD74 monoclonal antibody linked via a cleavable valine-citrulline polyethylene glycol linker to an MCL-1 inhibitor payload, specifically S64315 (also known as MIK665). CD74 is highly expressed on the surface of malignant hematologic cells but has limited expression in normal tissues. Upon binding to CD74, the ADC is internalized by cancer cells, where it releases the MCL-1 inhibitor payload. This leads to inhibition of MCL-1, a protein that promotes cell survival by inhibiting proapoptotic proteins; its inhibition triggers apoptosis in cancer cells. Preclinical studies have shown potent antitumor activity both as monotherapy and in combination with venetoclax. As of early 2025, S227928 is being evaluated in phase 1/2 clinical trials for relapsed/refractory AML, CMML, and MDS/AML patients who are no longer candidates for standard therapies.

Other names

CD74-Mcl-1 ADCCD-74-Mcl-1 ADCCD 74-Mcl-1 ADCMIK665-conjugated anti-CD74 ADCMIK-665-conjugated anti-CD74 ADCMIK 665-conjugated anti-CD74 ADC