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SMI#9

Development stage: Preclinical
Lead developer: Wayne State University
Modality: Small Molecules

Overview

SMI#9 is a small molecule inhibitor selective for Rad6 (specifically Rad6B), an ubiquitin-conjugating enzyme. Rad6B is a positive regulator of β-catenin stability; it induces K63-linked polyubiquitination of β-catenin, preventing its proteasomal degradation. By inhibiting Rad6B, SMI#9 leads to decreased levels of β-catenin and its downstream transcriptional targets, such as vimentin, Mitf-M, and Melan A. In melanoma models, SMI#9 treatment impairs cell migration and invasion and suppresses melanomagenesis. It was developed by researchers at Wayne State University and the Karmanos Cancer Institute.

Targets

UBE2B (Ubiquitin-conjugating enzyme E2 B)

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