DC-U4106

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].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> Cell Cycle/DNA Damage >> Deubiquitinase

Kd: 4.7 μM (USP8), IC50: 1.2 μM (USP8)[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.