6RK73

6RK73 is a covalent irreversible and specific UCHL1 inhibitor with an IC50 of 0.23 µM. 6RK73 shows almost no inhibition of UCHL3 (IC50=236 µM). 6RK73 specifically inhibit UCHL1 activity in breast cancer[1].

Research Areas >> Cancer

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

IC50: 0.23 µM (UCHL1), 236 µM (UCHL3)[1]

6RK73 (5 µM; 1-3 hours) treatment displays strong inhibition of the TGFβ-induced pSMAD2 and pSMAD3, and a decrease of TβRI and total SMAD protein levels in MDA-MB-436 cells[1]. 6RK73(5 µM; 24-48 hours) results migration significantly slower than the DMSO control group in MDA-MB-436 cells[1]. Cell Viability Assay[1] Cell Line: MDA-MB-436 cells Concentration: 5 µM Incubation Time: 24, 48 hours Result: Migrated significantly slower than the DMSO control group Western Blot Analysis[1] Cell Line: MDA-MB-436 cells Concentration: 5 µM Incubation Time: 1, 2, 3 hours Result: Displayed strong inhibition of the TGFβ-induced pSMAD2 and pSMAD3, and a decrease of TβRI and total SMAD protein levels.

6RK73 displays a potent inhibition of breast cancer extravasation in zebrafish[1].

[1]. Liu S, et al. Deubiquitinase activity profiling identifies UCHL1 as a candidate oncoprotein that promotes TGFβ-induced breast cancer metastasis. Clin Cancer Res. 2019 Dec 19. pii: clincanres.1373.2019.