ZSH-2208 is a synthetic analog of all-trans retinoic acid (ATRA) designed to overcome resistance and improve differentiation therapy in acute promyelocytic leukemia (APL) and other malignancies. In published studies, ZSH-2208 has shown superior anti-proliferative and pro-differentiation activity compared to ATRA in ATRA-resistant APL cell lines such as NB4-R2. For example, ZSH-2208 induced significant G1 phase arrest and granulocytic differentiation in NB4-R2 cells at concentrations around 1–10 µM, whereas ATRA was largely ineffective at equivalent doses. In mouse xenograft models, ZSH-2208 treatment led to marked tumor growth inhibition without the rapid metabolic degradation seen with ATRA. These data suggest that ZSH-2208 is a promising candidate for treating retinoic acid-resistant leukemias and potentially other cancers sensitive to retinoid signaling.
