PMB212 (IND) : Removing seed of cancers

The flagship candidate, PMB212, is a PIN1 inhibitor, developing as a cancer-stemness blocking agent. Pin1 is a pluripotential target for cancer stemness. It participates in pathways that up-regulate over 50 oncogenic proteins and down-regulate over 20 tumor suppressor proteins. Despite of involving in many pathways, its knockout animals grow normally. Pin1 is overexpressed in cancer cells of most cancer types, and even more so in cancer-stem-cells. In cellular studies, PMB212 kills specifically cancer cells with higher stemness. In the view of MoA, PMB212 blocks expression of cyclinD1 and ABC transporters, EMT process, and cancer-stemness related pathways including Wnt, Notch, HedgeHog, Hippo, STAT3, NFkB and BMI1, resulting in the inhibition of cancer-stemness markers. Such pluripotential actions of PMB212 would be different from the failed previous approaches to target a single pathway ignoring heterogeneity, complexity, and plasticity of cancer stem cells. In animal studies, PMB212 has shown efficacy in blocking tumor growth and metastasis. PMB212 has completed GLP-toxicity studies and submitted IND recently.