PPI Pharmaceuticals develops cancer therapeutics by exploiting protein-protein interactions, focused on protein kinases deregulated in oncology.REPLACE is the technology that makes more of those targets accessible.

From August 2025 to the present, PPI Pharmaceuticals is investigating abbapolin PLK1 polo-box domain inhibitors as potential therapeutics for colorectal cancers. National Cancer Institute grant R41CA298584 has two aims: medicinal chemistry optimization of the abbapolin leads, and testing their activity against colorectal cancers, including a panel of patient-derived organoids.

A Phase I STTR from May 2017 to May 2021, Polo-box PLK1 inhibitors targeting tumors resistant to ATP-competitive compounds, provided full in vivo validation of the REPLACE strategy in prostate cancer. Orally dosed abbapolins showed no overt signs of toxicity, and 6369 and 6190 produced a statistically significant reduction in PC-3 xenograft tumor volume. In the NCI-60 panel, abbapolins 6157, 6171, and 6190 were active against prostate, CNS, and colorectal lines, but not breast lines.

A Phase II grant applied for in September 2026, $2.5 million over two years, would determine in vivo activity in a colon cancer model.