P2/3, N=30, Recruiting, M.D. Anderson Cancer Center | Active, not recruiting --> Recruiting | N=11 --> 30

P1, N=32, Recruiting, Capital Medical University | Not yet recruiting --> Recruiting

We verify the structure using mutagenesis and confirm that the conformation corresponds to the active state of the receptor. Subsequent study of TrkB interaction with the antidepressant drug fluoxetine, and the antipsychotic drug chlorpromazine, provides a clear self-consistent model, describing the mechanism by which fluoxetine activates the receptor by binding to its transmembrane domain.

P1, N=32, Not yet recruiting, Capital Medical University

Previous studies have shown that chlorpromazine (CPZ) can inhibit YAP1 expression...Collectively, our findings indicate that FOXP3 competitively binds TEAD4 to regulate YAP1 localization in the nucleus and cytoplasm to suppress NPC progression. Consequently, FOXP3 may be a prognostic indicator for HNSCC.

We conclude that a therapeutic window for dopamine receptor antagonists in combination with radiation potentially exists, making it a novel combination therapy against glioblastoma. Normal tissue toxicity following this treatment scheme likely differs depending on age and sex and should be taken into consideration when designing clinical trials.

P3, N=100, Recruiting, Benaroya Research Institute | Not yet recruiting --> Recruiting

P4, N=60, Completed, All India Institute of Medical Sciences, Bhubaneswar | Recruiting --> Completed

P2, N=350, Active, not recruiting, LB Pharmaceuticals Inc. | Recruiting --> Active, not recruiting

P=N/A, N=338, Suspended, The Affiliated Hospital of Shandong Second Medical University; The Affiliated Hospital of Shandong Second Medical University | Not yet recruiting --> Suspended

Disrupting this loop via pharmacological targeting of ASCT2 or glutaminase, in combination with pimozide, induces remarkable mitochondrial damage and oxidative stress, leading to GBM cell death in vitro and in vivo. Our findings underscore the promising therapeutic potential of effectively targeting GBM by combining glutamine metabolism inhibition with lysosome suppression.

P3, N=100, Not yet recruiting, Benaroya Research Institute

P=N/A, N=200, Completed, Central South University | Recruiting --> Completed

P=N/A, N=200, Completed, Central South University | Recruiting --> Completed

Chlorpromazine potentiates the cytotoxic effects of the alkylating agent temozolomide through a mechanism involving downregulation of Cx43 expression and disruption of the cell cycle arrest essential for DNA repair processes. This finding suggests that chlorpromazine may be a potential therapeutic strategy to overcome TMZ resistance in GBM cells by inhibiting their DNA repair mechanisms.

P3, N=0, Withdrawn, Centre Hospitalier St Anne | N=40 --> 0 | Unknown status --> Withdrawn

P2/3, N=11, Active, not recruiting, M.D. Anderson Cancer Center | Enrolling by invitation --> Active, not recruiting | N=150 --> 11

P2, N=350, Recruiting, LB Pharmaceuticals Inc. | Trial completion date: Dec 2025 --> Jan 2025 | Trial primary completion date: Sep 2025 --> Oct 2024

This is one of the few published cases of COVID-19 associated persistent hiccups, occurring more than a month after the initial presentation. Most of the published cases report hiccups occurring in the acute COVID-19 period. Consequently, hiccups occurring in the post-acute COVID-19 period may not be attributable to COVID-19. This case has highlighted the need to consider post-acute COVID-19 in the differential diagnosis of persistent hiccup.

In conclusion, our results demonstrate that OXCT1 epigenetically suppresses antitumor immunity, suggesting that suppressing OXCT1 activity in TAMs is an effective approach for treating liver cancer.

Taurine and COQ-10 alone notably improved the antioxidant/anti-inflammatory status relative to controls. Among other mechanisms, taurine and COQ-10 abated CPZ-induced hematological deficiencies, via decreased serum levels of oxidative stress, and pro-inflammatory cytokines release, with increased antioxidants and anti-inflammation function.

P2/3, N=410, Recruiting, Acacia Pharma Ltd | Not yet recruiting --> Recruiting | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Jun 2024 --> Jun 2025

P4, N=102, Terminated, Sumitomo Pharma (Suzhou) Co., Ltd. | N=248 --> 102 | Recruiting --> Terminated; Company's business decision

Based on our findings, a mechanism of cell death was not able to be established due to lack of cleaved caspase-3 expression. Capable of bypassing many aspects of the lengthy, costly, and difficult cancer drug approval process, chlorpromazine and prazosin deserve further investigation for use in conjunction with traditional chemotherapeutics.

Endocytosis inhibitors identified that Monensin and Chlorpromazine hydrochloride significantly reduced MM-ZC internalization...Overall, the current study provides valuable insights into the cellular uptake and intracellular trafficking of MM-ZC in myeloma cells. Identifying these mechanisms and molecular players involved in MM-ZC uptake contributes to a better understanding of the delivery and potential applications of cell-specific Zip-Codes in gene delivery and drug targeting in cancer research.

P2, N=155, Completed, Integrative Research Laboratories AB | Phase classification: P2b --> P2

The knockdown of RAF1 expression induced autophagy and apoptosis in breast cancer cells, consistent with the results of pimozide or sorafenib alone. Blocked autophagy by chloroquine resulted in the impairment of pimozide-induced apoptosis. These data showed that pimozide inhibits breast cancer by regulating the RAF/ERK signaling pathway and might activate cAMP-induced autophagy to promote apoptosis and it may be a potential drug for breast cancer treatment.

Mechanistically, the direct binding of JX57 to GRP75 impairs the structure of the mitochondria-associated endoplasmic reticulum membrane and disrupts the endoplasmic reticulum-mitochondrial calcium homeostasis, resulting in a mitochondrial energy crisis and AMP-activated protein kinase activation. Taken together, these findings highlight GRP75 as a potential prognostic biomarker and direct therapeutic target in endometrial cancer and suggest that the chlorpromazine derivative JX57 can potentially be a new therapeutic option for endometrial cancer.

In this phase II clinical trial, we evaluated the addition of chlorpromazine to temozolomide in the adjuvant phase of the standard first-line therapeutic protocol in patients with unmethylated MGMT gene promoter. These findings provide proof-of-concept for the potential of adding CPZ to standard TMZ treatment in GBM patients with unmethylated MGMT gene promoter. https://clinicaltrials.gov/study/NCT04224441, identifier NCT04224441.

P2, N=350, Recruiting, LB Pharmaceuticals Inc.

The effect of CPZ can be epitomized as an inhibition of the Warburg effect and thus malignancy in GBM cells, while sparing RPE-1 cells. These preclinical data enforce the rationale that allowed us to investigate the role of CPZ in GBM treatment in a recent multicenter Phase II clinical trial.

P1, N=70, Completed, Whanin Pharmaceutical Company | .

P1, N=127, Completed, Simone Grimm | Not yet recruiting --> Completed

Amisulpride enhanced Wnt/GSK-3β/β-catenin signaling, increased BDNF levels, and abrogated 5-FU-induced neuroinflammation, apoptosis, β-amyloid accumulation, and neurodegenerative changes with an improvement of cognitive performance. This study draws attention to the pro-cognitive effects of amisulpride in 5-FU-exposed rats that could be attributed to enhancing hippocampal Wnt/GSK-3β/β-catenin signaling pathway, and this could offer a promising therapeutic option for subjects with CICI.

P1/2, N=266, Completed, Otsuka Pharmaceutical Development & Commercialization, Inc. | Phase classification: P1b --> P1/2

6,9). The addition of Chlorpromazine to temozolomide was well tolerated in newly diagnosed Glioblastoma unmethylated patients, with promising impact on outcome measures.

However, their phenotypic and functional similarity to their normal counterparts leaves limited road maps for their selective elimination. Tremblay and colleagues recently unraveled the fundamental role of overactivated pSTAT5 as a functional marker of ETP-ALL LSCs driving leukemic progression, and highlighted its potential use as a therapeutic target to prevent fatal outcomes.

P2/3, N=70, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Jun 2023 --> Jun 2025

P1, N=15, Recruiting, Mohammed Milhem | Trial completion date: Jun 2025 --> Jul 2024 | Trial primary completion date: Jun 2023 --> Jul 2024

Our study revealed that chronic stress accelerates GBM progression via DRD2/ERK/β-catenin axis and Dopamine/ERK/TH positive feedback loop. DRD2 together with β-catenin may serve as a potential predictive biomarker for worse prognosis as well as therapeutic target of GBM patients with depression.