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DRUG CLASS:

Protease inhibitor

12d
First in Human Study of TLC-ART 101 (ACTU 2001) (clinicaltrials.gov)
P1, N=12, Completed, University of Washington | Recruiting --> Completed | Trial completion date: Dec 2025 --> Jun 2024 | Trial primary completion date: Oct 2025 --> Jun 2024
Trial completion • Trial completion date • Trial primary completion date
17d
Identification of common core genes and pathways in childhood sepsis and cancer by bioinformatics analysis. (PubMed, Discov Oncol)
We identified genes with common effects on both childhood sepsis and cancer, which provides new insights into the association between sepsis and cancer. In addition, two drugs with potential clinical application value were identified. Further studies are required to validate the role of these common core genes in sepsis and cancer and to evaluate the potential utility of these drugs.
Journal • BRCA Biomarker
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TOP2A (DNA topoisomerase 2-alpha) • BRCA (Breast cancer early onset) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • IL10 (Interleukin 10) • ITGAM (Integrin, alpha M) • TLR4 (Toll Like Receptor 4) • MMP9 (Matrix metallopeptidase 9) • BCAT1 (Branched Chain Amino Acid Transaminase 1 ) • CDK1 (Cyclin-dependent kinase 1) • IL13 (Interleukin 13) • IL1B (Interleukin 1, beta) • IL4 (Interleukin 4) • ITGB2 (Integrin Subunit Beta 2) • TLR2 (Toll Like Receptor 2)
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TOP2A expression
25d
STARLITE for Unresectable High-Grade Gliomas (clinicaltrials.gov)
P1, N=24, Not yet recruiting, University of Miami | Trial completion date: May 2029 --> Mar 2030 | Initiation date: Nov 2024 --> Mar 2025 | Trial primary completion date: May 2028 --> Mar 2029
Trial completion date • Trial initiation date • Trial primary completion date
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temozolomide • ritonavir
28d
Oral Fosamprenavir + Sodium Alginate for GERD (clinicaltrials.gov)
P2, N=60, Not yet recruiting, Medical College of Wisconsin
New P2 trial
1m
Highly Active Antiretroviral Therapy for Patients With Primary Biliary Cirrhosis (clinicaltrials.gov)
P=N/A, N=13, Terminated, University of Alberta | Completed --> Terminated; Protracted gastrointestinal symptoms were experienced by most patients who were subsequently found to be in the treatment arm on LPV/r. This observation resulted in cessation of enrolment and a decision not to continue the RCT
Trial termination
1m
Therapeutic Effects of Different Doses of Ulinastatin in Acute Pancreatitis Patients (ChiCTR2400091262)
P=N/A, N=238, Not yet recruiting, The first affiliated hostipal of nanchang university; The first affiliated hostipal of nanchang university
New trial
1m
The efficacy and safety observation study of Eravacycline treatment in patients with neutropenia and fever: A multicenter retrospective cohort study based on HIS data (ChiCTR2400089338)
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
New trial
1m
Clinical efficacy of ulinastatin in the perioperative period of cardiopulmonary bypass in cardiac surgery: a retrospective real-world study (ChiCTR2400089064)
P=N/A, N=3000, Not yet recruiting, Beijing Anzhen Hospital Affiliated to Capital Medical University; Beijing Anzhen Hospital Affiliated to Capital Medical University
New trial • Real-world evidence • Surgery • Real-world
1m
Phase II clinical trial of lopinavir/ritonavir in patients with castration-resistant prostate cancer (ChiCTR2400089169)
P2, N=20, Not yet recruiting, Xiangya Hospital of Central South University; Xiangya Hospital of Central South University
New P2 trial
2ms
New trial
2ms
New trial • Real-world evidence • Real-world
2ms
Susceptibility of HPV-18 Cancer Cells to HIV Protease Inhibitors. (PubMed, Viruses)
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.
Journal
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ANXA5 (Annexin A5)
2ms
Regulatory Role of IL6 in Immune-Related Adverse Events during Checkpoint Inhibitor Treatment in Melanoma. (PubMed, Int J Mol Sci)
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.
Journal • Adverse events • Checkpoint inhibition
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PD-L1 (Programmed death ligand 1) • PD-1 (Programmed cell death 1) • IL6 (Interleukin 6) • IL6R (Interleukin 6 receptor)
2ms
Ulinastatin attenuates renal ischemia-reperfusion injury by inhibiting NLRP3 inflammasome-triggered pyroptosis. (PubMed, Int Immunopharmacol)
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.
Journal
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IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • IL18 (Interleukin 18) • NLRP3 (NLR Family Pyrin Domain Containing 3)
2ms
MALT1 protease inhibition restrains glioblastoma progression by reversing tumor-associated macrophage-dependent immunosuppression. (PubMed, bioRxiv)
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.
Journal
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MALT1 (MALT1 Paracaspase)
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temozolomide
2ms
Crystallization and crystallographic studies of human serine protease inhibitor (serpin) B9. (PubMed, Acta Crystallogr F Struct Biol Commun)
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.
Journal
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GZMB (Granzyme B)
3ms
Topical Protease Inhibitor Increases Tumor-Free and Overall Survival in CD4-Depleted Mouse Model of Anal Cancer. (PubMed, Viruses)
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.
Preclinical • Journal
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CD4 (CD4 Molecule)
3ms
A Study in Healthy Volunteers to Evaluate the Safety, Tolerability, Pharmacokinetics, and Drug-Drug Interaction Potential of Single and Multiple Doses of ALG-097558 (clinicaltrials.gov)
P1, N=144, Active, not recruiting, Aligos Therapeutics | Recruiting --> Active, not recruiting | Trial completion date: Jul 2024 --> Nov 2024
Enrollment closed • Trial completion date
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itraconazole • midazolam hydrochloride
3ms
Eravacycline improves the efficacy of anti-PD1 immunotherapy via AP1/CCL5 mediated M1 macrophage polarization in melanoma. (PubMed, Biomaterials)
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.
Journal • PD(L)-1 Biomarker • IO biomarker
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CCL5 (Chemokine (C-C motif) ligand 5) • MAPK8 (Mitogen-activated protein kinase 8)
3ms
The Late Presenter Treatment Optimisation Study (clinicaltrials.gov)
P3, N=447, Completed, NEAT ID Foundation | Active, not recruiting --> Completed
Trial completion • Metastases
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CD4 (CD4 Molecule)
4ms
Metformin, Nelfinavir, and Bortezomib in Treating Patients With Relapsed and/or Refractory Multiple Myeloma (clinicaltrials.gov)
P1, N=9, Completed, Mayo Clinic | Active, not recruiting --> Completed | Trial completion date: Aug 2024 --> Nov 2023
Trial completion • Trial completion date • Combination therapy
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SLC2A4 (Solute Carrier Family 2 Member 4)
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bortezomib • Viracept (nelfinavir)
4ms
Combining ulinastatin with TIENAM improves the outcome of sepsis induced by cecal ligation and puncture in mice by reducing inflammation and regulating immune responses. (PubMed, Int Immunopharmacol)
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.
Preclinical • Journal
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CD8 (cluster of differentiation 8) • IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • IL1B (Interleukin 1, beta)
4ms
BI-LIGHT: Study Evaluating the Safety, in Terms of HBV Virological Control at 96 Weeks, of 2 Antiviral Treatment Relief Strategies, in Patients Co-infected With the HIV-1 and HBV Viruses (clinicaltrials.gov)
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
Trial completion date • Trial initiation date • Trial primary completion date
5ms
Inhibition of human DNA alkylation damage repair enzyme ALKBH2 by HIV protease inhibitor ritonavir. (PubMed, DNA Repair (Amst))
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.
Journal
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ALKBH2 (AlkB Homolog 2)
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ritonavir
5ms
Oral Fosamprenavir-Sodium Alginate for LPR (clinicaltrials.gov)
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
Phase classification • Trial completion date • Trial primary completion date
5ms
Use of protease substrate specificity screening in the rational design of selective protease inhibitors with unnatural amino acids: Application to HGFA, matriptase, and hepsin. (PubMed, Protein Sci)
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.
Journal
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ST14 (ST14 transmembrane serine protease matriptase)
5ms
SCALOP-2: Systemic Therapy and Chemoradiation in Advanced Localised Pancreatic Cancer - 2 (clinicaltrials.gov)
P1/2, N=159, Completed, University of Oxford | Unknown status --> Completed | N=289 --> 159
Trial completion • Enrollment change • Metastases
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KRAS (KRAS proto-oncogene GTPase)
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gemcitabine • capecitabine • albumin-bound paclitaxel • Viracept (nelfinavir)
5ms
Effect and mechanism of dexmedetomidine and ulinastatin combined with healthy lateral position on pulmonary complications in patients with pulmonary lobectomy under thoracic microscope (ChiCTR2300074039)
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
Phase classification • Enrollment change
6ms
HIV-protease inhibitors potentiate the activity of carfilzomib in triple-negative breast cancer. (PubMed, Br J Cancer)
Proteasome inhibition by carfilzomib combined with nelfinavir/lopinavir represents a potential treatment option for TNBC, warranting further investigation.
Journal
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ABCB1 (ATP Binding Cassette Subfamily B Member 1) • ABCG2 (ATP Binding Cassette Subfamily G Member 2) • XBP1 (X-box-binding protein 1)
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bortezomib • carfilzomib • Viracept (nelfinavir)
6ms
Minimal involvement of P-gp and BCRP in oral absorption of ensitrelvir, an oral SARS-CoV-2 3C-like protease inhibitor, in a non-clinical investigation. (PubMed, J Pharm Sci)
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.
Journal
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ABCB1 (ATP Binding Cassette Subfamily B Member 1)
7ms
Oral Docetaxel (ModraDoc/r) in Combination With Hormonal Treatment and Radiation Therapy in High-risk Prostate Cancer (clinicaltrials.gov)
P1, N=24, Terminated, The Netherlands Cancer Institute | Unknown status --> Terminated; low inclusion of patients and availability of the IP
Trial termination • Combination therapy
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docetaxel oral/ritonavir (ModraDoc006/r) • ritonavir
7ms
TheraCRAB: Therapeutic Options for CRAB (clinicaltrials.gov)
P4, N=108, Not yet recruiting, Clinical Hospital Centre Zagreb
New P4 trial
7ms
Lopinavir/Ritonavir in PLWH With High-Grade AIN (clinicaltrials.gov)
P1, N=21, Recruiting, University of Wisconsin, Madison | Trial completion date: Dec 2024 --> Jun 2025 | Trial primary completion date: Jun 2024 --> Jun 2025
Trial completion date • Trial primary completion date
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CD4 (CD4 Molecule)
7ms
STARLITE for Unresectable High-Grade Gliomas (clinicaltrials.gov)
P1, N=24, Not yet recruiting, University of Miami
New P1 trial
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temozolomide • ritonavir
7ms
High expression of serine protease inhibitor kazal type 1 predicts poor prognosis and promotes the progression and invasion of oral tongue squamous cell carcinoma. (PubMed, Arch Oral Biol)
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.
Journal
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SPINK1 (Serine peptidase inhibitor, kazal type 1)
8ms
Rapid Reinitiation of a Single Tablet Antiretroviral Therapy Using Symtuza® in HIV-1 Infected Treatment-Experienced Patients Off Therapy. (ReSTART) (clinicaltrials.gov)
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
Trial completion • Trial completion date • Trial primary completion date
8ms
PPP2R1A silencing suppresses LUAD progression by sensitizing cells to nelfinavir-induced apoptosis and pyroptosis. (PubMed, Cancer Cell Int)
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.
Journal
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PPP2R1A (Protein Phosphatase 2 Scaffold Subunit Aalpha)
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Viracept (nelfinavir)