Platform programs

PDK1 Inhibitors
The PDK1 inhibitor PHT-427 has entered IND enabling studies

RAS Inhibitors
Through a genome wide screen for selective inhibitors of mutant KRAS, two novel druggable PH domain target proteins have been identified around which PHusis has developed discovery programs.

CNKSR1
CNKSR1 has been shown as a critical protein anchoring mutant KRAS in its plasma membrane signaling nanocluster allowing its activation and downstream signaling. PHusis has identified low micromolar inhibitors that are selectively active in mutant KRAS cell lines. Lead optimization is underway.

PLEK
The PH-domain of PLEK has also been identified as critical for the activation of mutant KRAS. PHusis has resolved crystal structure of the PLEK PH domain and has begun a screening discovery program against this novel drug target. Lead selection is anticipated in the next 12 months.

RAL Inhibitors
RalGEF and/or Ral activation is involved in KRAS-mediated activation of various signaling targets. The PH-domain of regulators of RAL activity has provided PHusis a novel approach to RAL inhibitor.