CBPD-268 is an effective orally active CBP/p300 PROTAC degrader, with a DC50 value of ≤ 0.03 nM. It induces degradation of CBP/p300 and inhibits cell growth, exhibiting antitumor activity. Additionally, CBPD-268 shows potential for research in AR-positive prostate cancer.

CBPD-268 demonstrates high degradation efficiency on CBP and p300 proteins in 22Rv1 cells with DC50 values of 0.01 and 0.03 nM, respectively, after 4 hours. The compound achieves degradation by binding to CBP/p300 and CRBN proteins. Additionally, CBPD-268 (0-1000 nM; 4 days) inhibits cell growth with IC50 values of 3.7, 10.3, and 4.6 nM in 22Rv1, LNCaP, and VCaP cells, respectively.

CBPD-268, administered orally at doses of 0.3, 1, 3, to 10, and 30 mg/kg as a single dose, induces degradation of CBP and p300 proteins in tumor tissues. When given at 1 mg/kg twice a week or 3 mg/kg weekly for 4 weeks, CBPD-268 shows antitumor activity.