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.

P=N/A, N=100, Enrolling by invitation, Wroclaw Medical University | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

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.

P4, N=368, Not yet recruiting, Aga Khan University

P3, N=222, Recruiting, Affiliated Hospital of Qinghai University | Initiation date: Sep 2025 --> Feb 2026

This case underscores the importance of considering MEN1 even in elderly patients with atypical manifestations, emphasizes the value of integrating prior medical history into diagnosis, and suggests a potential role of rs2959656 in MEN1 pathogenesis.

P2, N=90, Recruiting, Jazz Pharmaceuticals | Not yet recruiting --> Recruiting

The findings demonstrate that CLZ exerts neuroprotective effects in an LPS-induced rat model, improving cognition through modulation of cholinergic transmission, oxidative stress, and apoptosis pathways. These results clarify key mechanistic pathways through which CLZ may exert cognitive benefits and highlight its potential relevance for improving schizophrenia-related cognitive dysfunction. Further molecular studies are warranted to confirm and extend these observations toward clinical translation.

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.

In our MEN1 cohort, PitNETs were frequent but largely indolent, with a predominance of microadenomas and limited need for surgery. Our findings support individualized, subtype-driven surveillance strategies, with conservative management for clinically non-functioning microadenomas and closer monitoring of prolactin-secreting PitNETs due to variable medical responsiveness.

P4, N=5, Terminated, Ohio State University | N=60 --> 5 | Trial completion date: Jun 2026 --> Jan 2026 | Recruiting --> Terminated; Not able to recruit enough subjects