Program
One focused program. Two lead branches.
Isoform-selective PHD1 inhibitors for chemoresistance in microsatellite-stable colorectal cancer.
Lead-generation pipeline
EBP-4 — tool compound
Computationally designed PHD1 binder validating the design method: engages the p53 axis and suppresses MSS CRC proliferation in HCT-116.
Branch A — in silico lead series
Selectivity-optimized scaffold with three additive design mechanisms; docking-predicted PHD1 preference, pending enzymatic confirmation.
Branch B — synthesis-ready series
Homophthalimide analogs with PHD1 and PHD2 poses in hand and a non-chelating binding mode; prioritized for synthesis with Enamine.
Development path
Aim 1 — Target engagement & selectivityCell-based p53-axis engagement + HIF counter-screen; outsourced enzymatic IC₅₀ across PHD1/PHD2/PHD3.
Aim 2 — Chemo-potentiationCombination with oxaliplatin and SN-38 across p53-wild-type and p53-mutant MSS CRC models.
Toward IND-enablingLead optimization, then IND-enabling studies as data and funding support — plan-contingent, not a fixed schedule.
Future directions may extend PHD/EGLN biology beyond oncology; the current focus is MSS CRC.