A Selective Small Molecule Mcl-1 Inhibitor

Target: Induced myeloid leukemia cell differentiation protein (Mcl-1) /BH3 antiapoptotic interaction

  • Functional target class: MCL1 overexpression and interaction with BH3 is heavily implicated in survival and therapy resistance of tumor cells via inhibition of apoptosis
  • Goal: Development of BH3 SMOL mimetics disrupting Mcl-1-BH3 interaction, acting as apoptosis sensitizers and overcoming therapy resistance
  • Therapeutic area: Oncology
  • Indication: Several cancers (melanoma, myeloma, NSCLC, HCC)
  • Administration: oral
  • Combination therapy: optional but potentially especially with targeted therapies known for rapid resistance development
  • 347PXN0209 shows high activity in proprietary in-vitro and in-vivo assays
  • In-vitro: IC50 = 1.2µM Best in class
  • In-vivo: IC50 = 2.2 µM
  • Selectivity against BclXL: > 32-fold
  • Co-crystallization experiments in progress



The induced myeloid leukemia cell differentiation protein (Mcl-1) is a member of the Bcl-2 family of anti-apoptotic proteins. The overexpression of Mcl1 plays an essential role in survival and therapy resistance of tumor cells. Mcl1 acts by binding to BH3-domain of pro-apoptotic "BH3-only" proteins (Bad, Bim, Bid, PUMA, NOXA).

Mcl1 is a target of very high interest for all cancer researchers from big pharma to academia. Consequently the development of BH3-mimetic small molecules which disrupt Mcl1-BH3 interaction and act as apoptosis sensitizers to overcome resistance is one of Priaxon's leading projects.




Kang M. et al. Clin Cancer Res. 2009; 15(4): 1126-1132