| Identification | Back Directory | [Name]
Spiro[imidazolidine-4,1'-[1H]indene]-2,5-dione, 1-[2-[(3S)-7-fluoro-2,3-dihydro-3-(trifluoromethyl)-1,4-benzoxazepin-4(5H)-yl]-2-oxoethyl]-2',3'-dihydro-5'-(1-methyl-1H-pyrazol-4-yl)-, (1'S)- | [CAS]
2379416-48-3 | [Synonyms]
B026
Spiro[imidazolidine-4,1'-[1H]indene]-2,5-dione, 1-[2-[(3S)-7-fluoro-2,3-dihydro-3-(trifluoromethyl)-1,4-benzoxazepin-4(5H)-yl]-2-oxoethyl]-2',3'-dihydro-5'-(1-methyl-1H-pyrazol-4-yl)-, (1'S)- | [Molecular Formula]
C27H23F4N5O4 | [MOL File]
2379416-48-3.mol | [Molecular Weight]
557.5 |
| Hazard Information | Back Directory | [Uses]
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]. | [in vivo]
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 |
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| [IC 50]
p300: 8.1 nM (IC50); CBP: 9.5 nM (IC50) | [References]
[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. DOI:10.1021/acs.jmedchem.9b01721 |
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