XYD190 (Compound 14g) is an orally active degrader of CBP/p300. It inhibits the bromodomain of CBP/p300 with an IC50 of 483.7 nM and demonstrates antitumor activity against acute myeloid leukemia.

XYD190, at concentrations ranging from 0 to 1 μM over 72 to 120 hours, inhibits the proliferation of acute myeloid leukemia (AML) cells MV4;11, MOLM-13, and MOLM-16, with IC50 values of 1.8, 26.9, and 4.6 nM, respectively. Additionally, at concentrations of 0 to 150 nM for 6 hours, XYD190 induces the degradation of CBP and p300 in the bromodomain protein family in a CRBN and protease-dependent manner.

CBP/p300 ligand 4, administered orally at 5 mg/kg every other day for two weeks, demonstrates antitumor activity in the MV4;11 xenograft mouse model, achieving a tumor growth inhibition (TGI) rate of 88%.