For research use only. Not for therapeutic Use.
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].
I-138 (0.5 μM; 4 h) eliminates USP1 self-lysis in HAP-1 USP1 WT and knockout cells[1].I-138 (0.5 μM; 4 h) induces the monoubiquitination of FANCD2 and PCNA in MDA-MB-436 cells[1]. (0.01-10 μM; 10 days) dose-dependently inhibits MDA-MB-436 cells viability and don’t affect HCC1954 cells[1].
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].
| Catalog Number | I041282 |
| CAS Number | 2098211-50-6 |
| Synonyms | 9-[[4-[1-methyl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]-2-(2-propan-2-ylphenyl)-7H-purin-8-one |
| Molecular Formula | C26H23F3N6O |
| Purity | ≥95% |
| InChI | InChI=1S/C26H23F3N6O/c1-15(2)18-6-4-5-7-19(18)22-30-12-20-24(33-22)35(25(36)31-20)13-16-8-10-17(11-9-16)23-32-21(14-34(23)3)26(27,28)29/h4-12,14-15H,13H2,1-3H3,(H,31,36) |
| InChIKey | MVCJEDLGJGHLJM-UHFFFAOYSA-N |
| SMILES | CC(C)C1=CC=CC=C1C2=NC=C3C(=N2)N(C(=O)N3)CC4=CC=C(C=C4)C5=NC(=CN5C)C(F)(F)F |
| Reference | [1]. Simoneau A, et al. Ubiquitinated PCNA Drives USP1 Synthetic Lethality in Cancer. Mol Cancer Ther. 2023 Feb 1;22(2):215-226. |
