XYD198 (Compound 14h) is an orally active degrader of CBP/p300. It inhibits the CBP/p300 bromodomain with an IC50 of 213.5 nM and exhibits antitumor activity against acute myeloid leukemia.

XYD198 effectively inhibits the proliferation of acute myeloid leukemia (AML) cells MV4;11, MOLM-13, and MOLM-16 at concentrations ranging from 0 to 1 μM over 72 to 120 hours, with IC50 values of 0.9, 47, and 5.5 nM, respectively. Additionally, XYD198 at 0 to 150 nM over 6 hours induces degradation of the bromodomain proteins CBP and p300 in a CRBN and proteasome-dependent manner.

In a MV4;11 xenograft mouse model, CBP/p300 ligand 4 (5 mg/kg, orally, administered once every two days for two weeks) demonstrated antitumor activity, achieving a tumor growth inhibition (TGI) rate of 93%.