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

A combination of MD-derived pharmacophores and structure-based strategy identifies dual allosteric inhibitors of NS2B-NS3 proteases in Zika and West Nile viruses. (PubMed, Eur J Med Chem) - "Biochemical evaluation identified several inhibitors, with the antiretroviral drug Nelfinavir emerging as the most promising compound...The activity observed across flavivirus proteases highlights the value of targeting conserved allosteric regions. Overall, this integrated computer-aided drug design (CADD) strategy demonstrates the power of dynamic, structure-based pharmacophores to uncover novel allosteric inhibitors and accelerate antiviral drug repurposing."

Journal • Infectious Disease

Repurposing Nelfinavir: AIM2 inflammasome-associated anti-tumor effects in Glioblastoma. (PubMed, Biochim Biophys Acta Mol Basis Dis) - "We further evaluated the anti-tumor potential of NFR in combination with standard chemotherapeutic agents, carboplatin and doxorubicin, across these platforms. However, activation of the AIM2 inflammasome alone is not essential to induce its anti-tumor effects in GBM. Collectively, our findings highlight NFR as a promising therapeutic candidate for GBM, exerting its effects through anti-proliferative and pro-death mechanisms."

Journal • Brain Cancer • Glioblastoma • Glioma • Human Immunodeficiency Virus • Infectious Disease • Oncology • Solid Tumor

Betulinaldehyde Ameliorates Aβ-Induced Neurotoxicity and Cognitive Deficits by Modulating the eEF2K/eEF2 Pathway. (PubMed, CNS Neurosci Ther) - "These findings demonstrate that Betu protects against Aβ42-induced neurotoxicity by modulating the eEF2K/eEF2 pathway, highlighting its potential as a lead compound for AD."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Aβ42 • EEF2K • HMOX1

A Priori Design, Combinatorial Synthesis, and Assessment of an Antipackaging Peptide Against Human Immunodeficiency Virus 1: Functional Role of Unnatural Trp Mimetics and Serendipitous Discovery of a Protease Inhibitor. (PubMed, ChemMedChem) - "Instead, our best analog (IC50 2.84 µM) was a potent protease inhibitor, comparable to FDA-approved Lopinavir (1.44 µM) and Nelfinavir (1.54 µM). Together, our studies demonstrate the perils that can accompany early-phase discovery efforts, and the serendipitous findings that can sometimes result. They also showcase the power of unnatural tryptophan mimics to imbue unique antiretroviral structure-activity."

Journal • Human Immunodeficiency Virus • Infectious Disease

Causal association and molecular mechanisms of periodontal disease and muscle wasting and atrophy: Mendelian randomization and bioinformatics analysis. (PubMed, Front Genet) - "These are only the results of the preliminary virtual screening, including rofecoxib, TT-301 and nelfinavir. This relationship is mediated by chronic inflammation centered on IL-6, IL-1β, and IL-10 within the PI3K-Akt pathway. The findings provide a translational foundation for dual-targeting therapeutic strategies."

Journal • Dental Disorders • Inflammation • Muscular Atrophy • Periodontitis • IL10 • IL1B • IL6

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: May 2027 ➔ May 2028 | Trial primary completion date: May 2026 ➔ May 2027

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

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."

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

Combined treatment with PG3 and Nelfinavir induced synergistic apoptosis though sustained activation of integrated stress response (AACR 2024) - "The combined treatment sustained the induction of ATF4 and enhanced the expression of its proapoptotic target genes, CHOP and PUMA, and cell apoptosis. We confirmed that the enhanced induction of ATF4, CHOP and PUMA is through the ISR because ISRIB (ISR inhibitor) blocked the combined treatment-induced upregulation of ATF4, CHOP and PUMA."

Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • ATF4 • PPP1R15A

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

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

Risk Assessment for Drug-Induced Hyperbilirubinemia: A Mechanistic Approach. (PubMed, CPT Pharmacometrics Syst Pharmacol) - "Model simulations linked nilotinib-induced hyperbilirubinemia to UGT1A1 mutations, and simulations were used to assess the risk of hyperbilirubinemia associated with varying doses of nelfinavir, atazanavir, and TAK-875, based on their off-target effects on transporters. Results demonstrated that uncertainty in free drug tissue concentration may be crucial in hyperbilirubinemia, especially for highly protein-bound drugs. This approach may help assess hyperbilirubinemia risk using a drug's inhibitory in vitro data coupled with patient pharmacogenetic data for OATP1B1, UGT1A1, and MRP2 mutations."

Journal • Genetic Disorders • ABCC3 • UGT1A1

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

Trial completion • Cervical Cancer • Oncology • Solid Tumor • Uterine Cancer

NIBAN2/FLII/RREB1 Axis Drives Glioma Stem Cell Malignancy via TLR3 Pathway Activation. (PubMed, Adv Sci (Weinh)) - "Drug screening identified the HIV protease inhibitor nelfinavir as a specific disruptor of the NIBAN2-FLII complex...Collectively, this study, for the first time, reveals that NIBAN2 maintains GSCs stemness by activating FLII-RREB1 axis and TLR3 signaling, thereby establishing a feed-forward signaling-transcription-metabolism axis. This finding provides a novel strategy and potential targets for precise therapeutic intervention against glioma stemness."

IO biomarker • Journal • Brain Cancer • Glioblastoma • Glioma • Human Immunodeficiency Virus • Infectious Disease • Oncology • Solid Tumor • CD44 • LDHA • RREB1 • SOX2 • TLR3

Potency-enhancing mutations in E3-19K and i-leader increase the cytolytic activity of the PH20/SPAM1-armed oncolytic adenovirus Ad5Δ24RGD. (PubMed, Mol Ther Oncol) - "In some cell lines, the fiber modification F5RGD10(2C) or verapamil treatment further improves actual spread efficiency. Nelfinavir inhibits spread and plaque formation of oncolytic adenoviruses with the 19KSS-iLQ125Ter modifications, irrespective of adenovirus death protein (ADP) expression...We identified an insertion site downstream of the L3-23K region that supports relatively high hPH20 activity while preserving the enhanced oncolytic potency of the virus. Combining 19KSS-iLQ125Ter with hPH20 expression may potentially improve therapeutic benefit in glioma."

Journal • Brain Cancer • Glioblastoma • Glioma • High Grade Glioma • Oncology • Solid Tumor • SPAM1

Molecular docking and dynamic simulation of marine natural products from soft coral-derived microbes against SARS-CoV-2 main protease and spike protein. (PubMed, Sci Rep) - "Many of the test compounds [e.g., Cottoquinazoline B and D (CQB/D), Tetraorcinol A (TOA), Versicoloritide A and C (VCA/C), Fumiquinazoline K, and Pencillanthranin A) showed stronger binding affinities compared to control antiviral drugs (nelfinavir and remdesivir) and formed favorable interactions with both Mpro and the RBD of S-protein. Molecular dynamics (MD) simulation (200 ns) analysis further revealed stable binding conformations of the top docked complexes of (1) CQB with Mpro, (2) CQB with the RBD of WT S-protein, (3) TOA with the RBD of S-protein from beta variant (4) TOA with the RBD of S-protein from Omicron variant, (5) TOA with the RBD of S-protein from Delta variant, (6) TOA with the RBD of S-protein from Gamma variant, and (7) VCA with the RBD of alpha variant. However, future in vitro and in vivo studies are still required to validate efficacy of these compounds."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

NELCER: Radiosensitizing Effect of Nelfinavir in Locally Advanced Carcinoma of Cervix (clinicaltrials.gov) - P3 | N=348 | Active, not recruiting | Sponsor: Tata Memorial Hospital | Trial completion date: Jan 2026 ➔ Apr 2026

Trial completion date • Cervical Cancer • Oncology • Solid Tumor • Uterine Cancer

Forecasting drug resistant HIV protease evolution. (PubMed, PLoS Comput Biol) - "Our analysis shows that the dual therapy of Atazanavir (ATV) and Ritonavir (RTV) is the multi-PI treatment regimen least likely to induce drug resistance. Interestingly, our results highlight the necessity of the amino-acid polymorphism of L63P by predicting that it is critical in developing resistance to Nelfinavir (NFV). The results validate that our framework effectively extracts and combines biological information from the distinct data sets of observed genotypes and drug resistance, while also tackling the challenge of sparsity of available sequence data compared to the large combinatorial complexity of protein evolution and changing functionality in dynamic environments."

Journal • Human Immunodeficiency Virus • Infectious Disease

An Overview of the Mechanisms of HPV-Induced Cervical Cancer: The Role of Kinase Targets in Pathogenesis and Drug Resistance. (PubMed, Cancers (Basel)) - "In particular, Aurora kinases A, B, and C (ARKA, ARKB, and ARKC), phosphotidylinositol-trisphosphate kinase (PI3K)-Akt, and Glycogen synthase kinase3-α/β (GSK3 α/β) promote the transformation of infected cells, and also enhance the resistance of cells to various chemotherapeutic agents such as nelfinavir and cisplatin. Given the critical role of kinases in the pathogenesis and treatment of CC, a comprehensive review of current evidence is warranted. This review aims to provide key insights into the mechanisms of HPV-induced CC development, the involvement of kinases in drug resistance induction, and the rationale for combination therapies to improve clinical outcomes."

Journal • Review • Cervical Cancer • Oncology • Solid Tumor • Targeted Protein Degradation

NELCER: Radiosensitizing Effect of Nelfinavir in Locally Advanced Carcinoma of Cervix (clinicaltrials.gov) - P3 | N=348 | Active, not recruiting | Sponsor: Tata Memorial Hospital | Trial completion date: Sep 2025 ➔ Jan 2026

Trial completion date • Cervical Cancer • Oncology • Solid Tumor • Uterine Cancer

Autophagy Maintenance (AUTOMAIN) (clinicaltrials.gov) - P2 | N=38 | Recruiting | Sponsor: Medical University of South Carolina | Not yet recruiting ➔ Recruiting | N=20 ➔ 38 | Trial completion date: Dec 2027 ➔ Jun 2029 | Trial primary completion date: Dec 2026 ➔ Jun 2028

Enrollment change • Enrollment open • Platinum sensitive • Trial completion date • Trial primary completion date • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor

Darunavir analog precursors target mitochondrial metabolism in multiple myeloma and CLL. (PubMed, Cancer Cell Int) - "BupM-NH2, and particularly BnpM-NH2, showed enhanced cytotoxicity against MM, CLL, and NDMM cells compared to PBMCs by inducing apoptosis through autophagy and mitochondrial respiration inhibition. While the cytotoxic effect in RRMM is less pronounced and nonsignificant, BupM-NH2 and BnpM-NH2 induces stress in respiratory chain and mitochondria, which may re-sensitize resistant tumor cells to treatments. Therefore these compounds may hold promise as novel therapeutic agents for MM and CLL treatment."

Journal • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Human Immunodeficiency Virus • Infectious Disease • Leukemia • Multiple Myeloma • Oncology • ANXA5

Treating Anemia in Myelofibrosis With Repurposed Drugs (Nelfinavir) That Restore Iron Delivery to the Bone Marrow (clinicaltrials.gov) - P1/2 | N=10 | Recruiting | Sponsor: University of California, Irvine

New P1/2 trial • Anemia • Hematological Disorders • Myelofibrosis

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