B026

B026 is a selective, potent, orally active p300/CBP histone acetyltransferase (HAT) inhibitor with IC50 values of 1.8 nM and 9.5 nM for p300 and CBP enzyme, respectively. B026 has anticancer activity for androgen receptor-positive (AR+) prostate cancer cell lines[1].

Research Areas >> Cancer

Signaling Pathways >> Epigenetics >> Histone Acetyltransferase

p300:8.1 nM (IC50)

CBP:9.5 nM (IC50)

B026 (0-5 μM; 12 h; cancer cell lines) has antiproliferative activity[1]. B026 (0-5 μM; 6 h; MV-4-11 cells) exhibits inhibitory effects on H3K27Ac expression[1]. B026 (0-5 μM; 12 h; MV-4-11 cells) targets the cellular p300 protein and increases the thermal stability of p300 protein in a dose-dependent manner[1]. B026 (0-1 μM; 24 h; MV-4-11 cells) decreases the expression of MYC, which a key oncogenictranscription factor that is regulated by superenhancer regions containing p300/CBP[1]. Cell Viability Assay[1] Cell Line: Maver-1, MV-4-11, K562, Kasumi-1, LnCaP-FGC and 22Rv1 cells Concentration: 0-5 μM Incubation Time: 12 hours Result: Inhibited cell growth with IC50 values of 2.6, 4.2, 4.4, 9.8, 40.5 and 104.4 nM for Maver-1, MV-4-11, 22Rv1, LnCaP-FGC, Kasumi-1 and K562 cells, respectively. Western Blot Analysis[1] Cell Line: MV-4-11 cells Concentration: 0, 0.313, 0.625, 1.25, 2.5 and 5 μM Incubation Time: 6 hours Result: Decreased the expression of H3K27Ac in a dose-dependent manner.

B026 (1-3 mg/kg; i.v. and p.o.; 0-24 h; male SD rats) has a low clearance (13.4 mL/min/kg) and good oral exposure (AUC=3.71 μM·h) with good oral bioavailability (F=56%) in rat[1]. B026 (50-100 mg/kg; p.o.; daily, for 28 days; balb/c female mice) inhibits tumor growth in a dose-dependent manner[1]. Animal Model: Balb/c female mice with MV-4-11 xenograft[1] Dosage: 50 and 100 mg/kg Administration: Oral administration; daily, for 28 days Result: Inhibited tumor growth with TGI of 75.0% at 50 mg/kg and 85.7% at 100 mg/kg, respectively. Animal Model: Male SD rats[1] Dosage: 1 and 3 mg/kg Administration: Intravenous injection and oral administration; 0.25, 0.5 , 1 , 2 , 4 , 8 and 24 hours Result: 1.19 Administration i.v. (1 mg/kg) p.o. (3 mg/kg) T1/2 (h) 1.5 1.02 Tmax (h) 0.83 Cmax (μM) 1.12 AUClast (μM·h) 2.22 3.71 Vdss (L/kg) 1.5 CL_obs (mL/min/kg) 13.4 PPB % 98.2 F % 56

[1]. Yang Y, et, al. Discovery of Highly Potent, Selective, and Orally Efficacious p300/CBP Histone Acetyltransferases Inhibitors. J Med Chem. 2020 Feb 13;63(3):1337-1360.