Pharmacological inhibitors of specific USPs, such as pimozide, trifluoperazine, rottlerin, 6-thioguanine, and costunolide, are highlighted for their potential to inhibit proliferation, metastasis, induce apoptosis, and circumvent therapy resistance across breast cancer subtypes (triple-negative and HER-2 positive). The review highlights the complex and often contradictory roles of USPs in breast cancer and points to the immense promise of targeting these enzymes to develop new and efficacious anticancer therapies.

This further suggests that if chlorpromazine binding alters coupling between the PAS/CNBH domain ring, VSD and pore, as predicted by the network analysis, these alterations occur at potential more depolarized than the ones eliciting the Cole-Moore shift. Taken together, our study provides an insight into the allosteric pathways of EAG1 channel regulation by small molecule PAS domain binders.

We demonstrate that CPZ, alone or in combination with temozolomide (TMZ), the current standard of care, activates the cGAS-STING signaling pathway, thus promoting anti-tumor immune responses. This study uncovers that CPZ exerts a previously unrecognized anti-cancer immunomodulatory activity, remodeling the immune microenvironment and enhancing the anti-tumor immune response. By overcoming TMZ resistance, CPZ not only exerts a direct anti-neoplastic effect, but also sensitizes GBM cells to standard therapy.

Pimozide exerts anticancer effects through coordinated disruption of nucleocytoplasmic transport, proteostasis regulation, and matrix remodeling. These findings support the repositioning of pimozide as a multi-target anticancer agent and provide a mechanistic foundation for further translational investigation.

Empagliflozin protects brain function after CA by enhancing oxidative metabolism of ketone body, and its underlying mechanism is associated with reducing neuroinflammation and improving mitochondrial energy metabolism. These findings suggest that empagliflozin may represent a novel therapeutic strategy for mitigating brain injury following CA.

This study uncovered a novel oncogenic axis in neuroblastoma, where NeuroD1 transcriptionally upregulates USP1, promoting N-Myc stabilization and tumor progression. Furthermore, the findings highlight the therapeutic potential of repurposing Pimozide as a promising treatment strategy for this aggressive tumor subtype.

P4, N=1, Terminated, University of Miami | N=60 --> 1

P2, N=180, Active, not recruiting, Central Institute of Mental Health, Mannheim | Recruiting --> Active, not recruiting | Trial completion date: Jun 2026 --> Dec 2027 | Trial primary completion date: Jun 2026 --> Dec 2027

P=N/A, N=104, Not yet recruiting, Huashan Hospital Fudan University; Huashan Hospital Fudan University

P3, N=900, Not yet recruiting, LB Pharmaceuticals Inc.

P3, N=456, Not yet recruiting, LB Pharmaceuticals Inc.

P1, N=100, Not yet recruiting, Stanford University