CD123-CPI dimer ADC

A **CD123-targeted antibody-drug conjugate (ADC)** comprising an anti-CD123 monoclonal antibody covalently linked, via a cleavable linker, to a dimer of the cytotoxic payload **cyclopropylpyrroloindoline (CPI)**. Upon binding to CD123—overexpressed on leukemic blasts and leukemic stem cells (LSCs), particularly in **acute myeloid leukemia (AML)**—the ADC is internalized. In the endosomal-lysosomal pathway, proteolytic cleavage releases the CPI dimer payload, which crosslinks and alkylates DNA, leading to activation of DNA damage response pathways (ATM/ATR, CHK1, CHK2, FANCD2) and subsequent **tumor cell death**. The conjugate is designed to maximize selective cytotoxicity against CD123+ malignant cells while sparing normal hematopoietic cells. Preclinical studies, primarily by Pfizer, indicate robust anti-leukemia activity and a favorable toxicity profile versus other ADCs such as those targeting CD33[1][5][9].

Other names

CD123-CPI dimer ADCCD-123-CPI dimer ADCCD 123-CPI dimer ADCCD123-ADCCD-123-ADCCD 123-ADCAnti-CD123 monoclonal antibody CPI conjugateAnti-CD-123 monoclonal antibody CPI conjugateAnti-CD 123 monoclonal antibody CPI conjugateAnti-CD123-CPIAnti-CD-123-CPIAnti-CD 123-CPI