P=N/A, N=238, Not yet recruiting, The first affiliated hostipal of nanchang university; The first affiliated hostipal of nanchang university

P=N/A, N=200, Not yet recruiting, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College; Institute of Hematology and

P=N/A, N=3000, Not yet recruiting, Beijing Anzhen Hospital Affiliated to Capital Medical University; Beijing Anzhen Hospital Affiliated to Capital Medical University

P2, N=20, Not yet recruiting, Xiangya Hospital of Central South University; Xiangya Hospital of Central South University

P2, N=40, Recruiting, Code Pharma

P=N/A, N=50, Not yet recruiting, Peking University Third Hospital

P=N/A, N=100, Not yet recruiting, Sichuan Provincial People's Hospital

Therefore, the use of HIV drugs, particularly HIV-1 protease inhibitors, as potential cancer therapeutics represents a promising strategy. This is supported by our study demonstrating their anticancer properties, notably in HPV-associated cervical cancer cell line.

Furthermore, we conducted an integrative network and molecular-level analysis, including virtual screening, of drug libraries, such as the Collection of Open Natural Products (COCONUT) and the Zinc15 FDA-approved library, to identify potential IL6 inhibitors. Subsequently, the compound amprenavir was identified as the best molecule that may disrupt essential interactions between IL6 and IL6R, which are responsible for initiating the signaling cascades underlying irAEs in ICI therapies.

We further revealed that UTI could inhibit NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome activation by increasing the expression of nuclear factor-κB (IκB) kinase-alpha (IKKα) interacting with apoptosis-associated speck-like protein containing CARD (ASC) to alleviate kidney damage. These findings provide evidence of the renoprotective role of UTI in cardiac surgery-associated (CSA)-AKI, which is associated with the inhibition of NLRP3 inflammasome activation by upregulating IKKα.

Further, the addition of MALT1 inhibitor to temozolomide reduces immunosuppression in the tumor microenvironment, which may enhance the efficacy of this standard-of-care chemotherapeutic. Together, our findings suggest that MALT1 protease inhibition represents a promising macrophage-targeted immunotherapeutic strategy for the treatment of GBM.

The structure shows that serpin B9 adopts a relaxed conformation, with its cleaved reactive-centre loop inserted into the central β-sheet. Unlike other serpins, serpin B9 shows significant structural deviations around helix D, with a larger surface cavity, which could serve as a promising target for small-molecule inhibitors.

Transgenic K14E6/E7 mice with established high-grade anal dysplasia were treated topically at the anus with the protease inhibitor saquinavir (SQV) in the setting of CD4+ T-cell depletion to mimic immunodeficiency...The CD4-depleted mice treated with DMBA had significantly increased tumor-free survival and overall survival as well as decreased tumor-volume growth over time when treated with SQV. These data suggest that topical SQV, in the setting of CD4 depletion and high-grade anal dysplasia, can increase tumor-free and overall survival; thus, it may represent a viable topical therapy to decrease the risk of progression of anal dysplasia to anal cancer.

P1, N=144, Active, not recruiting, Aligos Therapeutics | Recruiting --> Active, not recruiting | Trial completion date: Jul 2024 --> Nov 2024

As expected, application of ERV improved the efficacy of anti-PD1. Overall, our results approved that ERV enhances the efficacy of anti-PD1 immunotherapy in melanoma by promoting the polarization of M1 macrophages, which provided novel therapeutic strategy for improving the effectiveness of melanoma anti-PD1 immunotherapy.

P4, N=16, Not yet recruiting, Huashan Hospital, Fudan University; Huashan Hospital, Fudan University

P3, N=447, Completed, NEAT ID Foundation | Active, not recruiting --> Completed

P1, N=16, Not yet recruiting, Aligos Therapeutics

P1, N=9, Completed, Mayo Clinic | Active, not recruiting --> Completed | Trial completion date: Aug 2024 --> Nov 2023

The use of conventional antibiotics such as TIENAM (imipenem and cilastatin sodium for injection, TIE) is challenging because of the increasing bacterial resistance, which diminishes their efficacy and leads to adverse effects. Our findings indicate that UTI and TIE combination therapy can significantly enhance sepsis outcomes by reducing inflammation and boosting the immune system. The results offer a promising therapeutic approach for future sepsis treatment.

P2, N=140, Not yet recruiting, ANRS, Emerging Infectious Diseases | Trial completion date: Feb 2027 --> Sep 2027 | Initiation date: May 2024 --> Oct 2024 | Trial primary completion date: Feb 2027 --> Sep 2027

Interestingly, we observed that one of the inhibitors, ritonavir, could inhibit ALKBH2-mediated DNA repair significantly via competitive inhibition and sensitized cancer cells to alkylating agent methylmethane sulfonate (MMS). This work may provide new insights into the possibilities of utilizing HIV protease inhibitor ritonavir as a DNA repair antagonist.

P2, N=104, Not yet recruiting, Medical College of Wisconsin | Phase classification: P3 --> P2 | Trial completion date: Oct 2025 --> Apr 2026 | Trial primary completion date: Oct 2025 --> Feb 2026

The tripeptide inhibitor PK-1-89 (2) has excellent pharmacokinetics in mice with good compound exposure out to 24 h. In addition, we obtained an X-ray structure of the inhibitor MM1132 (15) bound to matriptase revealing an interesting binding conformation useful for future inhibitor design.

P1/2, N=159, Completed, University of Oxford | Unknown status --> Completed | N=289 --> 159

P=N/A, N=500, Recruiting, Union Hospital affiliated to Fujian Medical University; Union Hospital affiliated to Fujian Medical University | Phase classification: P1 --> P=N/A | N=252 --> 500

P2/3, N=26, Completed, University of Liverpool | Active, not recruiting --> Completed

Proteasome inhibition by carfilzomib combined with nelfinavir/lopinavir represents a potential treatment option for TNBC, warranting further investigation.

Based on our previous retrospective analyses, such a low AUC ratio (<3) in the Mdr1a/1b (-/-) mice indicates a minimal impact of P-gp on the oral absorption in humans. In conclusion, our studies demonstrate that the involvement of both P-gp and BCRP in the oral absorption of ensitrelvir is minimal, and suggest that ensitrelvir has a low risk for DDIs mediated by P-gp and BCRP inhibition in humans.

P1, N=24, Terminated, The Netherlands Cancer Institute | Unknown status --> Terminated; low inclusion of patients and availability of the IP

P4, N=108, Not yet recruiting, Clinical Hospital Centre Zagreb

P1, N=21, Recruiting, University of Wisconsin, Madison | Trial completion date: Dec 2024 --> Jun 2025 | Trial primary completion date: Jun 2024 --> Jun 2025

P1, N=24, Not yet recruiting, University of Miami

Suppression of SPINK1 inhibited OTSCC cell proliferation, invasion, and motility while promoting apoptosis. These findings suggest that SPINK1 may serve as a prognostic biomarker as well as a potential therapeutic target for managing OTSCC.

P4, N=75, Completed, The Crofoot Research Center, Inc. | Active, not recruiting --> Completed | Trial completion date: Dec 2023 --> Apr 2024 | Trial primary completion date: Sep 2023 --> Apr 2024

Additionally, repression of PPP2R1A enhances cellular susceptibility to nelfinavir-induced apoptosis and pyroptosis. Collectively, our findings indicated that meiosis-related genes might be therapeutic targets in LUAD and provided crucial guidelines for LUAD clinical intervention.

P2, N=135, Completed, Modra Pharmaceuticals | Phase classification: P2b --> P2 | N=102 --> 135

P1, N=22, Not yet recruiting, Cytonics Corporation | Initiation date: Mar 2024 --> Jun 2024

P2, N=140, Not yet recruiting, ANRS, Emerging Infectious Diseases

After adjustment, abnormal PHF19 post induction treatment was independently related to shortened EFS (hazard ratio = 2.474) and OS (hazard ratio = 3.124). PHF19 is aberrantly high and declines post induction therapy, which simultaneously reflects unfavorable treatment response to protease inhibitors as well as shorter EFS and OS in MM patients.

These results improve the understanding of the TME of pancreatic cancer and provide a foundation for further studies on intratumoral heterogeneity. In addition, differentially expressed gene secretory leukocyte protease inhibitor (SLPI) was identified in pancreatic cancer, and functional experiments showed that SLPI had a strong impact on cell viability and apoptosis, which offers a potential therapy target for pancreatic cancer.

P3, N=104, Not yet recruiting, Medical College of Wisconsin | Trial completion date: Oct 2024 --> Oct 2025 | Trial primary completion date: Oct 2024 --> Oct 2025