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PPAP #122

Development stage: Preclinical
Lead developer: Kantonsspital St. Gallen
Modality: Small Molecules

Overview

PPAP #122 is a synthetic Type-B polycyclic polyprenylated acylphloroglucinol (PPAP-B) developed for the treatment of acute myeloid leukemia (AML), particularly to overcome resistance to venetoclax. It functions by inducing the mitochondrial apoptosis pathway, characterized by BAX activation, cytochrome C release, and cleavage of caspases 8 and 3. Mechanistically, it suppresses the transcription of anti-apoptotic proteins MCL-1 and BCL-XL, potentially through the inhibition of the JAK-STAT signaling pathway. PPAP #122 has demonstrated high synergy with venetoclax in both in vitro and ex vivo AML models, including venetoclax-resistant cell lines, while maintaining low toxicity and favorable physicochemical properties such as water solubility and photochemical stability.

Other names: Type-B polycyclic polyprenylated acylphloroglucinol #122

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