Karthik Selvaraju

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Inhibition of deubiquitinase (DUB) activity is a promising strategy for cancer therapy. VLX1570 is an inhibitor of proteasome DUB activity currently in clinical trials for relapsed multiple myeloma. Here we show that VLX1570 binds to and inhibits the activity of ubiquitin-specific protease-14 (USP14) in vitro, with comparatively weaker inhibitory activity(More)
Although more traditionally associated with degradation and maintenance of protein homeostasis, the ubiquitin-proteasome system (UPS) has emerged as a critical component in the regulation of cancer cell growth and survival. The development of inhibitors that block the proteolytic activities of the proteasome have highlighted its suitability as a bona fide(More)
“We are grateful to Hans Rosén and Per Hagmar (Vivolux AB) for discussions and study support and to Marina Ciomei (Accelera, Nerviano, Italy) for performance of animal studies. We are grateful to Ingrid Holmberg for artwork. We acknowledge Cancerfonden, Radiumhemmets forskningsfonder, Vetenskapsrådet, Barncancerfonden for support. We would like to(More)
The non-genotoxic nature of proteasome inhibition makes it an attractive therapeutic option for the treatment of pediatric malignancies. We recently described the small molecule VLX1570 as an inhibitor of proteasome deubiquitinase (DUB) activity that induces proteotoxic stress and apoptosis in cancer cells. Here we show that acute lymphoblastic leukemia(More)
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