FBXW17 Inhibitors

The chemical class termed FBXW17 Inhibitors encompasses a group of compounds that can indirectly influence the activity of FBXW17 through modulation of the ubiquitin-proteasome pathway. These compounds are not direct antagonists of FBXW17 but act on different components of the pathway that FBXW17 is a part of, primarily the proteasome itself or enzymes involved in the ubiquitination process. Proteasome inhibitors like MG132, Bortezomib, Lactacystin, Epoxomicin, Velcade, and Oprozomib can prevent the degradation of proteins that FBXW17 may target for ubiquitination, leading to their accumulation. This stabilization of substrates can indirectly reduce the functional impact of FBXW17 in cellular processes.

On the other hand, compounds such as PYR-41 and MLN4924 (Pevonedistat) target upstream elements of the ubiquitin-proteasome system. PYR-41 inhibits the E1 enzyme, necessary for the initiation of the ubiquitination cascade, whereas MLN4924 inhibits the neddylation of cullin proteins, which is crucial for the activation of cullin-RING ubiquitin ligases, a category to which the SCF complex containing FBXW17 belongs. Nutlin-3 affects the p53 pathway, potentially altering the pool of substrates available to FBXW17. Celastrol, Thalidomide, and Withaferin A modulate stress responses and protein turnover, thereby potentially altering FBXW17's role in protein homeostasis.