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Oncology

PMB212 (IND) : Removing seed of cancers

The flagship candidate, PMB212, is a PIN1 inhibitor being developed as an agent to block cancer stemness. Pin1 is the target protein and is involved in pathways that upregulate more than 50 oncogenic proteins and downregulate over 20 tumor suppressor proteins. Despite its involvement in numerous pathways, Pin1 knockout animals develop normally, likely because Pin1 does not activate all disease-related pathways simultaneously; instead, it only triggers pathways relevant to specific disease contexts. Under normal physiological conditions, the absence of Pin1 has minimal impact. Importantly, Pin1 is overexpressed in the cancer cells of most tumor types, with even higher expression in cancer stem cells.
In cellular studies, PMB212 selectively kills cancer cells with high stemness. Mechanistically, PMB212 blocks the expression of cyclin D1 and ABC transporters, inhibits the EMT process, and suppresses cancer stemness-related pathways including Wnt, Notch, Hedgehog, Hippo, STAT3, NFkB, and BMI1, resulting in the downregulation of cancer stemness markers. This broad mechanism of action distinguishes PMB212 from previous approaches that targeted only a single pathway, which often failed to address the heterogeneity, complexity, and plasticity of cancer stem cells. In animal studies, PMB212 has demonstrated efficacy in inhibiting tumor growth and metastasis. The compound has completed GLP-compliant toxicity studies and an IND application has recently been submitted.