LRK-4189

LRK-4189 is a first-in-class, orally bioavailable, selective small molecule degrader of the lipid kinase phosphatidylinositol 5-phosphate 4-kinase type II gamma (PIP4K2C). Developed by Larkspur Biosciences, LRK-4189 targets cancer cell fitness by inducing proteasomal degradation of PIP4K2C. This degradation disrupts tumor adaptive stress pathways, leading to intrinsic apoptosis, activation of interferon signaling, and stimulation of both intrinsic and immune-mediated cancer cell death. LRK-4189 has shown subnanomolar potency in primary human cells, demonstrated single-agent efficacy and synergy with standard-of-care chemotherapy in preclinical colorectal cancer models, and achieved a 50% response rate in primary CRC patient-derived spheroids—favorably compared to the benchmark cetuximab. It is being developed primarily for microsatellite stable (MSS) colorectal cancer and has completed IND-enabling studies, with a Phase 1 clinical trial slated for late 2025[1][2][3][4][5][7][8].

Other names

Compound 319 [WO2024233846]