| Identification | Back Directory | [Name]
7,9-Dihydro-2-[2-(1-methylethyl)phenyl]-9-[[4-[1-methyl-4-(trifluoromethyl)-1H-imidazol-2-yl]phenyl]methyl]-8H-purin-8-one | [CAS]
2098211-50-6 | [Synonyms]
I-138
7,9-Dihydro-2-[2-(1-methylethyl)phenyl]-9-[[4-[1-methyl-4-(trifluoromethyl)-1H-imidazol-2-yl]phenyl]methyl]-8H-purin-8-one | [Molecular Formula]
C26H23F3N6O | [MOL File]
2098211-50-6.mol | [Molecular Weight]
492.5 |
| Chemical Properties | Back Directory | [density ]
1.37±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted) | [form ]
Solid | [pka]
10.68±0.20(Predicted) | [color ]
White to light yellow |
| Hazard Information | Back Directory | [Uses]
I-138 is an orally active, reversible inhibitor of USP1-UAF1 (IC50: 4.1 nM; Ki: 5.4 nM), structurally related to ML323 (HY-17543). I-138 induces monoubiquitination of FANCD2 and PCNA in cells and eliminates USP1 autocleavage in cells[1]. | [in vivo]
I-138 (50 mg/kg/day; po, for 41 days) results USP1 inhibition and modest antitumor activity in mice bearing MDA-MB-436 tumors. However, the combination of I-138 and Niraparib (HY-10619), a PARP inhibitor, benefit the BRCA1/2 mutant tumors inhibition in vivo[1].
| [References]
[1] Simoneau A, et al. Ubiquitinated PCNA Drives USP1 Synthetic Lethality in Cancer. Mol Cancer Ther. 2023 Feb 1;22(2):215-226. DOI:10.1158/1535-7163.MCT-22-0409 |
|
|