Viracept (nelfinavir) / ViiV Healthcare, Roche - LARVOL DELTA

Results of an Open-Label Phase 1 Study Repurposing Oral Metformin and Nelfinavir in Combination with Subcutaneous Bortezomib in Patients with Relapsed and/or Refractory Multiple Myeloma (ASH 2023) - "This is the first study to evaluate the safety and efficacy of this repurposed drug combination in this very difficult-to-treat population of RRMM. While no ORR was observed, identification of biomarkers used for selection of patients with no other SOC options who could experience at least SD responses may be beneficial in allowing this combination to slow or stabilize the disease progression until other novel therapies or clinical trials are available."

Clinical • Combination therapy • IO biomarker • P1 data • Anemia • Fatigue • Hematological Malignancies • Multiple Myeloma • Pulmonary Disease • SLC2A4

Nelfinavir, Cisplatin, and External Beam Radiation Therapy for the Treatment of Locally Advanced Vulvar Cancer That Cannot Be Removed by Surgery (clinicaltrials.gov) - P1 | N=25 | Recruiting | Sponsor: M.D. Anderson Cancer Center | N=18 ➔ 25

Enrollment change • Gynecologic Cancers • Oncology • Solid Tumor • Vulvar Cancer

Insights into Antiviral Candidates against Oropouche Virus: A Molecular Dynamics Study. (PubMed, ACS Phys Chem Au) - "While docking initially ranked Saquinavir as the top binder, subsequent MD simulations revealed that nelfinavir and indinavir exhibited superior performance across multiple criteria, including binding energy, structural stability, center-of-mass distance maintenance, and consistent hydrogen bonding. These findings emphasize the limitations of docking-only approaches and highlight the importance of dynamic and energetic analyses for accurate inhibitor selection. The proposed computational pipeline demonstrates its value in identifying stable, high-affinity ligands and offers a promising route for accelerating drug discovery against neglected viral diseases such as OROV."

Journal • Human Immunodeficiency Virus • Infectious Disease

Nelfinavir triggers ferroptosis by inducing ER stress mediated downregulation of GPX4/GSH system, upregulation of NRF2/HO-1 axis, and mitochondrial impairment in hepatocellular carcinoma cells. (PubMed, Cell Death Discov) - "In a mouse model of HCC xenografts, nelfinavir treatment significantly suppressed tumor growth, and this effect was more pronounced when nelfinavir and sorafenib were administered together. Collectively, we demonstrate that nelfinavir can induce ferroptosis in an ER stress dependent manner, thereby identifying a new inducer of ferroptosis that can potentially be repurposed to treat HCC."

Journal • Hepatocellular Cancer • Human Immunodeficiency Virus • Infectious Disease • Oncology • Solid Tumor • GPX4 • HMOX1

COAST Therapy in Advanced Solid Tumors and Prostate Cancer (clinicaltrials.gov) - P1/2 | N=76 | Recruiting | Sponsor: Medical University of South Carolina | Trial completion date: Oct 2026 ➔ May 2027 | Trial primary completion date: Oct 2025 ➔ May 2026

Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Autophagy Maintenance (AUTOMAIN) (clinicaltrials.gov) - P2 | N=20 | Not yet recruiting | Sponsor: Medical University of South Carolina | Initiation date: Sep 2025 ➔ Jan 2026

Trial initiation date • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor

NELCER: Radiosensitizing Effect of Nelfinavir in Locally Advanced Carcinoma of Cervix (clinicaltrials.gov) - P3 | N=348 | Active, not recruiting | Sponsor: Tata Memorial Hospital | Recruiting ➔ Active, not recruiting

Enrollment closed • Cervical Cancer • Oncology • Solid Tumor • Uterine Cancer

QSPR graph model to explore physicochemical properties of potential antiviral drugs of dengue disease through novel coloring-based topological indices. (PubMed, Front Chem) - "Some of the promising antiviral drugs include UV-4B (N-9-methoxynonyl-1-deoxynojirimycin), Lycorine, ST-148, 4-HPR, Silymarin, Baicalein, Quercetin, Naringenin, Nelfinavir, Ivermectin, Mosnodenvir (JNJ-1802), NITD-688, Metoclopramide, JNJ-A07 and Betulinic acid. Linear regression is employed in the QSPR(Quantitative Structure Property Relationship) analysis to examine the dengue antivirals through the computed topological indices of the aforementioned drugs. The results of the QSPR analysis reveal that the induced color-based indices provide better predictions of the physicochemical properties of dengue-treating drugs."

Journal • Dengue Fever • Infectious Disease

Investigating the eEF2K/eEF2 axis as a potential target in CLL following nelfinavir treatment (IWCLL 2025) - "Our previous studies demonstrated that treatment of chronic lymphocytic leukaemia (CLL) cells with the mTORC1 inhibitor rapamycin, resulted in eEF2 inhibition (increased p-eEF2 T56) via elevated eEF2K activity, leading to reduced MCL1 expression...Combining NFR with the BTK inhibitor ibrutinib enhanced the anti-proliferative activity of NFR in MEC1 cells...In the WT-CLL mouse model, NFR significantly inhibited cell proliferation in vitro, while this trend was attenuated in eEF2K-KI-CLL cells, further strengthening the central role of eEF2K in the mechanism of action of NFR. In summary, our data demonstrate that NFR inhibits CLL cell proliferation and survival through the activation of eEF2K signaling, supporting the eEF2K/eEF2 axis as a potential therapeutic target and highlighting NFR as a novel treatment for CLL."

Chronic Lymphocytic Leukemia • Hematological Malignancies • Multiple Myeloma • EEF2K • MCL1

Autophagy Maintenance (AUTOMAIN) (clinicaltrials.gov) - P2 | N=20 | Not yet recruiting | Sponsor: Medical University of South Carolina | Initiation date: Jun 2025 ➔ Sep 2025

Platinum sensitive • Trial initiation date • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor

A Comprehensive Molecular Dynamic Simulation Study of Plant Bioactive Phytoconstituents as Inhibitors for SARS-CoV-2 Main Protease and Spike (S) Glycoprotein. (PubMed, Curr Comput Aided Drug Des) - "The current investigation discovered bioactive phytoconstituents derived from plants that have the potential to be developed as therapeutic alternatives for COVID-19."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Machine learning-based identification of exosome-related biomarkers and drugs prediction in nasopharyngeal carcinoma. (PubMed, Discov Oncol) - "This study identifies five exosome-related key genes, utilizing machine learning approaches to develop a diagnostic model and uncover potential drug targets for NPC. These findings offer novel perspectives for both the diagnosis and therapeutic development of NPC."

Biomarker • Journal • Nasopharyngeal Carcinoma • Oncology • Solid Tumor • CCL2 • IDH1 • LGALS3 • LGALS3BP

Repurposing of approved drugs towards Nipah virus treatment: an in silico docking, molecular dynamics simulation and a MM/GBSA approach. (PubMed, In Silico Pharmacol) - "Binding affinities and 2D interaction profiles were analyzed, revealing five promising candidates: Saquinavir, Nelfinavir, Simeprevir, Paritaprevir, and Tipranavir. To evaluate their efficacy and contribute to the development of effective antiviral treatments against NiV, further in vivo testing in animal models and human trials is recommended. The online version contains supplementary material available at 10.1007/s40203-025-00371-z."

Journal • CNS Disorders • Infectious Disease

Postnatal prophylaxis and the use of presumptive HIV therapy for the prevention of vertical transmission of HIV in Canada 1997-2020. (PubMed, J Int AIDS Soc) - "PHT has been widely used in Canada in situations at high risk of VT, with 25% of newborns in this risk group receiving PHT as PNP. While PHT may reduce the risk of VT in high-risk situations and may be of benefit in cases of VT, these data also highlight ongoing gaps in perinatal HIV prevention in Canada."

Journal • Human Immunodeficiency Virus • Infectious Disease

Autophagy Maintenance (AUTOMAIN) (clinicaltrials.gov) - P2 | N=20 | Not yet recruiting | Sponsor: Medical University of South Carolina

New P2 trial • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor

Chemoradiation and IGBT Alone or in combination with Protein Kinase inhibitor in Stage III Cervical cancer: Results for Phase III Randomized trial. (ESTRO 2025) - P3 | "CRT included Image guided-intensity modulated radiotherapy (IG-IMRT) (45Gy/25#) and nodal boost up to 55 Gy/25/5 weeks for involved nodes and concurrent weekly cisplatin (40 mg/m 2). Though the conservative statistical futility boundary was not violated at this preplanned interim analysis, the 3-year DFS of Nelfinavir arm was not considered clinically efficacious enough to support continued recruitment for the clinical trial."

Clinical • Combination therapy • P3 data • Cervical Cancer • Oncology • Solid Tumor

ER-phagy mediates the anti-tumoral synergism between HDAC inhibition and chemotherapy. (PubMed, Cell Commun Signal) - "In summary, we provide mechanistic evidence for ER-phagy playing a hitherto unknown central role in the clinical synergy between HDACi and chemotherapy."

Journal • Hematological Disorders • Hematological Malignancies • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor

Identification of potential SARS-CoV-2 inhibitors among well-tolerated drugs using drug repurposing and in vitro approaches. (PubMed, Sci Rep) - "Furthermore, dual combination experiments revealed that amcinonide, pimozide, lumacaftor, and eltrombopag acted as potent inhibitors at nanomolar concentrations when combined with candesartan. This study highlights lumacaftor, candesartan, and nelfinavir as effective inhibitors of SARS-CoV-2 replication in vitro and emphasizes their potential for repurposing as antiviral treatments. These findings support future clinical trials and may lead to breakthroughs in COVID-19 treatment strategies."

Journal • Preclinical • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Systems biology analysis of vitamin D3 reveals new anticancer properties (AACR 2025) - "This study provides a comprehensive in vitro examination of the cancer cell lines most impacted by treatment with vitamin D3. Further research will help better inform the use of vitamin D3 in nutrition plans and guide its use in cancer prevention and treatment."

Colorectal Cancer • Hematological Malignancies • Melanoma • Multiple Myeloma • Oncology • Solid Tumor • CTNNB1

Augmentation of statin-induced ATF4 stress response enhances the cancer cell-killing effect of statin (AACR 2025) - "These compounds include the endoplasmic reticulum (ER) stress sensor ATF6 activator, AA147, and the two ATF4 activators, Sal003 and Nelfinavir...Moreover, knocking down ATF4 was able to inhibit apoptosis and partially protect neuroblastoma cells from the effects of these drug combinations. These results suggest a strategy to enhance the anti-tumor effect of statins by amplifying ATF4 stress signaling to trigger apoptosis."

CNS Tumor • Neuroblastoma • Oncology • Solid Tumor • ATF3 • ATF4 • ATF6 • CASP3

The HIV protease inhibitor nelfinavir increases the sensitivity of epithelial ovarian cancer cells to cisplatin (AACR 2025) - "Cytosolic dsDNA is an activation signal for the AIM2 inflammasome; to confirm its involvement, EOC cells were incubated with CDDP and NFV in the presence or absence of the AIM2 inhibitor suramin. Resistance to apoptosis is a major mechanism by which EOC cells become Pt-resistant. Therefore, NFV and CDDP together, may be a feasible therapeutic option for these patients through the induction of pyroptosis."

Epithelial Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • ANXA5 • GSDME • IL1B

'Nelfinavir sensitizes a clinically relevant chemo-radioresistant cervical cancer in-vitro model by targeting the AKT-USP15/USP11-HPV16 E6/E7 axis. (PubMed, Biochem Biophys Rep) - "HPV16-positive SiHa cervical cancer cells were subjected to concurrent cisplatin and ionizing radiation, to simulate the clinical treatment regimen for locally advanced cervical cancer. Overall, this study successfully established a chemo-radioresistant SiHa cell model, providing a platform for investigating resistance mechanisms. It also highlights nelfinavir's potential as a therapeutic agent in overcoming chemo-radioresistance in cervical cancer."

Journal • Preclinical • Cervical Cancer • Human Immunodeficiency Virus • Infectious Disease • Oncology • Solid Tumor • USP11

KiBS: A Study of Zidovudine/Lamivudine and Either Nevirapine or Nelfinavir for Reduction of Mother-to-child HIV Transmission During Breastfeeding (clinicaltrials.gov) - P2 | N=520 | Completed | Sponsor: Centers for Disease Control and Prevention | Unknown status ➔ Completed

Trial completion • Human Immunodeficiency Virus • Infectious Disease • CD4

A Prospective Cohort of Children With HIV Infection (clinicaltrials.gov) - P=N/A | N=500 | Completed | Sponsor: The HIV Netherlands Australia Thailand Research Collaboration | Trial completion date: Jun 2024 ➔ Sep 2024 | Trial primary completion date: Jun 2024 ➔ Sep 2024 | Active, not recruiting ➔ Completed

Trial completion • Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease

ART Exposure and Accelerated Aging in PLHIV: Insights From Proteomic and Methylation Clocks (CROI 2025) - P | "Longer cumulative exposure to dolutegravir (DTG), rilpivirine (RPV) and nelfinavir (NFV) was associated with lower age advancement scores on at least a biological clock. In contrast, longer exposure to tenofovir disoproxil fumarate (TDF), emtricitabine (FTC), darunavir (DRV), atazanavir (ATV), and dideoxynucleoside analogues (d-drugs) was related to higher age advancement scores (Figure 1; P<0.05, adjusted for chronological age)...Conclusions Cumulative ART exposure influences age acceleration in PLHIV, with distinct effects across regimens and drug classes. Innate immune pathways appear to be key drivers of these effects and are promising therapeutic targets to mitigate accelerated aging."

Human Immunodeficiency Virus • Infectious Disease • Inflammation