DC-U4106 is a USP8 targeting inhibitor with the Kdvalue of 4.7 μM and the IC50 value of 1.2 μM. DC-U4106 can target the ubiquitin pathway and facilitate the degradation of Erα. DC-U4106 inhibits tumor growth with minimal toxicity and has the potential for the research of breast cancer[1].
DC-U4106 (1.2-45.2 μM) inhibits USP8 and USP2 with the IC50 values of 1.2 μM and 58.4 μM, respectively, and no activity in USP7[1].
DC-U4106 (0-7 μM, 24 hours) reduces mRNA levels of ERα and PR[1].
DC-U4106 (0-5 μM, 24 hours) can regulate the RTK pathway related proteins and the expression of ERα and PR proteins[1].
DC-U4106 (0-5 μM, 12 hours) can induce apoptosis and inhibit cell proliferation[1].
Western Blot Analysis[1]
| Cell Line: | USP8-positive cell line MCF-7 |
| Concentration: | 0-5 μM |
| Incubation Time: | 24 hours |
| Result: | Reduced the expression of EGFR, ErbB2, and ErbB3 proteins with increasing concentrations and caused degradation of ERα and PR proteins. |
RT-PCR[1]
| Cell Line: | USP8-positive cell line MCF-7 |
| Concentration: | 0-7 μM |
| Incubation Time: | 24 hours |
| Result: | Reduced mRNA levels of ERα and PR. |
Cell Proliferation Assay[1]
| Cell Line: | USP8-positive cell line MCF-7 |
| Concentration: | 0-5 μM |
| Incubation Time: | |
| Result: | Inhibited cell growth in a dose-dependent manner. |
Apoptosis Analysis[1]
| Cell Line: | USP8-positive cell line MCF-7 |
| Concentration: | 0-5 μM |
| Incubation Time: | 12 hours |
| Result: | Resulted in increasing in the proportion of apoptotic cells with increasing concentrations. |
DC-U4106 (intraperitoneal injection, 5 mg/kg or 20 mg/kg, every 2 days, 14 days) inhibits the proliferation of tumors and no significantly effects on body weight, organ morphology and structure in BALB/c nude mice[1].
| Animal Model: | BALB/c nude mice[1] |
| Dosage: | 5 mg/kg , 20 mg/kg |
| Administration: | Intraperitoneal injection, Every 2 days, 14 days |
| Result: | Inhibited tumor growth significantly at a concentration of 20 mg/kg. |
[1]. Yucheng Tian, et al. Discovery of Potent Small-Molecule USP8 Inhibitors for the Treatment of Breast Cancer through Regulating ERα Expression. J Med Chem. 2022 Jul 5.