Invirase (saquinavir) / Roche - LARVOL DELTA

N6- methyladenosine mRNA methylation of MPZL3 regulates EGFR signalling to mediate EGFR TKI resistance in EGFR-mutant lung adenocarcinoma (ERS 2026) - "Targeting MPZL3 with the identified inhibitor saquinavir restored EGFR degradation and synergized with osimertinib to overcome resistance in EGFR-mutant LUAD. Our findings establish a direct mechanism by which m6A-dependent regulation of MPZL3 drives EGFR TKI resistance. MPZL3 represents a promising predictive biomarker and therapeutic target for combating EGFR TKI resistance in EGFR-mutant LUAD."

Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MPZL3

An AI-Driven Chemogenomics Knowledgebase for Human-Transmissible Pathogens: A Platform for Antimicrobial Drug Discovery. (PubMed, J Chem Inf Model) - "In wet-lab validations, four approved drugs (cefixime, ceftazidime, saquinavir, and rilapladib) identified via virtual screening show binding activity to SARS-CoV-2 nucleoprotein in affinity assays and inhibit SARS-CoV-2 replication in Vero E6 cells, demonstrating HPM-CKB's potential in drug repurposing. Meanwhile, two anti-Staphylococcus aureus lead compounds with novel scaffolds (CYC-HXL-9124 and CYC-HXL-9126) are identified via deep learning, and the potential target protein, cell division protein FtsZ, is subsequently prioritized using HPM-CKB (http://cgai.asia/g/pathogenDB) and experimentally validated by affinity assays. Collectively, these findings establish HPM-CKB as both a chemogenomic knowledgebase and a systematic drug development platform against EIDs."

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

Saquinavir inhibits pyroptosis by regulating NLRP3 degradation to alleviate acute lung injury. (PubMed, Int Immunopharmacol) - "SQV alleviates sepsis-induced ALI by targeting OTUD6A to promote NLRP3 ubiquitination and degradation, thereby inhibiting macrophage pyroptosis via the NLRP3-caspase-1-GSDMD axis."

Journal • Acute Lung Injury • Critical care • Human Immunodeficiency Virus • Infectious Disease • Respiratory Diseases • Septic Shock • Targeted Protein Degradation • NLRP3

Physiological, Transcriptomic, and Metabolomic Insights into Ammonia-Nitrogen Stress in the Hepatopancreas of Litopenaeus vannamei Acclimated to Low Salinity. (PubMed, Biology (Basel)) - "In the secretion pathway, solute carrier family 4 (anion exchanger),member 2 (slc4a3) was strongly correlated with saquinavir and carnitine. In the metabolism pathway, nicotinamide/nicotinate riboside kinase (nmrk1), chitinase (chia), Gamma-glutamyltranspeptidase (ggt1), UDP-glucose 4-epimerase (gale), and spermine oxidase (smox) were linked to L-pyroglutamic acid, betaine, etc. In the immune pathway, mitogen-activated protein kinase 8/9/10 (bsk) and integrin beta 1 (cd29) were associated with leukotriene E4 and niacin. This study reveals that ammonia stress after low-salinity acclimation induces oxidative stress damage, elevated physiological changes in L. vannamei, and further elucidates the regulatory pathways underlying its response to ammonia nitrogen stress."

Journal • ITGB1 • MAPK8

Repurposing FDA-Approved Drugs as Potential Inhibitors of Feline Infectious Peritonitis Virus 3CLpro: An Integrated In Silico and In Vitro Study with Synergistic Combination Analysis. (PubMed, ACS Pharmacol Transl Sci) - "Synergy analysis with established anti-FIP agents (GC376, remdesivir, GS-441524, and molnupiravir) using SynergyFinder 3.0 revealed strong synergistic interactions: saquinavir + GC376 (mean ZIP score: 54.59), lumacaftor + GC376 (mean ZIP: 21.44), and gliquidone + remdesivir (mean ZIP: 24.13). These rational combinations enable substantial dose reduction, offering practical strategies to improve treatment accessibility, reduce costs, and minimize adverse effects. This study establishes a framework for repurposing FDA-approved drugs in FIP therapy and supports translational evaluation of these combination regimens."

FDA event • Journal • Preclinical • Infectious Disease • Novel Coronavirus Disease • IFNB1 • IL6 • TNFA

Repurposing Antiretroviral Drugs for Urological Cancers: Differential Effects of Protease Inhibitors and NNRTIs on Prostate and Bladder Cancer Cells. (PubMed, Cells) - "This study evaluated the anticancer potential of three antiretroviral drugs, namely ritonavir (RIT), saquinavir (SAQ), and rilpivirine (RPV), in PC-3 and UM-UC-5 cancer cell lines, using MTT, clonogenic, wound healing, toxicity assessment with fibroblast cells, and DCFDA assays; this last method included efavirenz (EFV) and etravirine (ETV) for intracellular reactive oxygen species (ROS) production. Generally, all drugs showed minimal toxicity in non-malignant cells, with SAQ exhibiting some toxicity but only for concentrations higher than those required for anticancer activity. Overall, these findings suggest that antiretroviral, especially protease inhibitors, may cause anticancer effects, although these are concentration- and context-dependent, and further investigation is needed to understand the mechanisms involved."

Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urethral Cancer

A 100 Million Cell Single Cell Atlas Enabling Mechanistic and Genotype-Specific Drug Response Discovery (EACR 2026) - "Stratification by genotype uncovers lineage- and mutation-specific responses, including unexpected dabrafenib sensitivity in additional cell lines not typically classified as BRAF-dependent...For example, transcriptional similarity mapping shows that saquinavir induces an adrenoceptor-agonist-like program, resembling vilanterol and norepinephrine, providing a molecular explanation for its known cardiovascular effects... By processing fixed cells in massive pooled batches, we minimized batch effects and enabled direct comparison across the entire perturbation space. Tahoe-100M establishes a new benchmark for large scale drug response mapping and provides a foundation for AI-driven discovery across human cell models."

Cardiovascular • BRAF

Interactions Among Drugs, Food, Beverages, Alcohol, Herbs, Phytochemicals, Nutraceuticals, and Micronutrients: A Current and Updated Review. (PubMed, Cardiovasc Hematol Agents Med Chem) - "The population of elderly, patients on drugs with patients on drugs with a narrow therapeutic window, pregnant women, and children needs more attention. To better assess the benefit-risk relationship, a full and comprehensive dietary recall, including simultaneous intake of drugs and food, is recommended."

Journal • Epilepsy

Re-Profiling and Re-purposing of FDA-Approved AntiViral Agents Against Neurological Targets of Memory and Cognition: Molecular Docking and Simulation Approach. (PubMed, CNS Neurol Disord Drug Targets) - "Based on the applied computational techniques on 69 FDA-approved agents, including molecular docking, SWISS-ADME, and MDS, we identified saquinavir, simeprevir, and paritaprevir as potential molecules modulating the action of AChE and BuChE to restore memory and cognition. Hence, it is supposed that these agents may serve as anti-Alzheimer agents. Further investigations are needed to find their therapeutic potential in in vitro and in vivo animal models."

FDA event • Journal • Alzheimer's Disease • CNS Disorders • Dementia • Infectious Disease • Pain

Downregulation of claudin-2 expression and chemoresistance by saquinavir in human lung adenocarcinoma cells. (PubMed, Eur J Pharmacol) - "In contrast, ritonavir, another HIV protease inhibitor, or raltegravir, an HIV integrase inhibitor, has no significant effect, indicating that inhibition of viral enzymes is not directly involved in the regulation of CLDN2 expression. Notably, SQV enhanced the cytotoxic effects of multiple anticancer agents, including doxorubicin, cisplatin, and SN-38, in lung adenocarcinoma cell line-derived spheroids and patient-derived organoids. We suggest that SQV improves chemoresistance by reducing CLDN2 expression and oxidative stress in lung adenocarcinoma."

Journal • Human Immunodeficiency Virus • Infectious Disease • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CLDN2 • NFE2L2

FDA-approved drug library screen identifies antidepressants, antimicrobials, anti-COPD, and anti-CVD agents as blockers of NLRP3 inflammasome and sepsis in a sex-dependent manner. (PubMed, bioRxiv) - "Various classes of drugs, such as antidepressants (Fluoxetine, Duloxetine), antihypertensives (Irbesartan, amlodipine, nebivolol), antidiabetics (Rosiglitazone), β-adrenergic agonists (Salmeterol), antimalarials (Mefloquine), antifungals (Azoles, ciclopirox), and antivirals (Saquinavir, Remdesivir), were identified as potent blockers of either priming or assembly of NLRP3 inflammasome. Mice treated with LPS-priming blockers showed a sex-specific increase in survival rate in the mouse model of LPS-induced mortality, validating the in vitro screen. Further studies in primary human cells and in vivo disease models are needed to assess the repurposing and therapeutic relevance of identified drugs."

FDA event • Journal • Alzheimer's Disease • Asthma • Chronic Obstructive Pulmonary Disease • CNS Disorders • Diabetes • Genetic Disorders • Gout • Immunology • Infectious Disease • Inflammatory Arthritis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Movement Disorders • Novel Coronavirus Disease • Obesity • Parkinson's Disease • Pulmonary Disease • Respiratory Diseases • Rheumatology • Septic Shock • NLRP3

Targeting RSV F and N Proteins: A Computational Approach to Identify Effective Antivirals (RSVVW 2026) - "For the F protein, we selected three ligands: Venetoclax, Nilotinib, and Saquinavir, with binding energies of which had a docking score of -9.20 kcal/mol, -11.56 kcal/mol, and -6.35 kcal/mol, and corresponding Ki values of 971.93 nM, 3.37 nM, and 22.00 µM, respectively. For the N protein, the selected ligands were Dutasteride, Conivaptan, and Ergotamine, with docking scores of -8.07 kcal/mol, -7.41 kcal/mol, and -8.59 kcal/mol, and Ki values of 1.21 µM, 3.71 µM, and 507.71 nM, respectively...Additionally, the Protein-Ligand Interaction Profiler revealed hydrophobic interactions between the ligands and the receptors. Our study proposes a suitable and innovative approach to combat RSV infection, warranting further validation through in vitro methods to fully establish efficacy."

Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

Repurposing amide-based drugs unveils inhibition mechanisms of plasmodium falciparum Plasmepsin V enzymatic activity for antimalarial therapy. (PubMed, Bioorg Chem) - "In this work, we investigated whether three approved amide-based drugs favipiravir, 5-fluorouracil (5-FU), and saquinavir could inhibit catalytic activity of PfPlmV. Favipiravir binds at the periphery of the cleft without engaging the catalytic dyad and therefore behaves as a weak, non-inhibitory binder. The insights of interaction-structure-inhibitory activity obtained from this study may guide repurposing strategies to develop selective potent inhibitors/antimalarial agents targeting PfPlmV."

Journal • Infectious Disease • Malaria

Saquinavir induces pyroptosis through the OTUD5-JAK1-GSDME axis in hepatocellular carcinoma. (PubMed, Free Radic Biol Med) - "Pyroptosis is a newly defined form of programmed cell death characterized by plasma membrane perforation, release of cellular contents, and a robust inflammatory response, thereby sensitizing tumors to existing anticancer therapies. Furthermore, the combination of SAQ with sorafenib, a first-line therapeutic agent for HCC, exhibited synergistic antitumor activity both in vitro and in the nude mouse model. These findings not only identify SAQ as a novel pyroptosis-inducer, but also clarify the critical role of the OTUD5-JAK1-GSDME axis in resisting pyroptosis, which may further provide experimental evidence and potential new strategies for treating HCC."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • CASP3 • GSDME • JAK1 • OTUD5

Repurposing of FDA-Approved Drugs to Identify Potential NS2B/NS3 Protease Inhibitors against Dengue Virus: In Silico and In Vitro Evaluation. (PubMed, Acta Trop) - "The three hits, Simeprevir, Saquinavir, and Dolutegravir of were subsequently evaluated for their cytotoxicity and antiviral activity in Vero cells, using MTT and infectivity-based assays, respectively. This study reflects on the potential of Dolutegravir as a dengue protease inhibitor and also indicates the efficacy of drug repurposing as a drug discovery strategy in the paradigm of antiviral discovery. Dolutegravir was identified as a potential candidate against DENV-2, and additional research is needed with molecular dynamics, mechanistic inquiry, and in vivo support investigation."

FDA event • Journal • Preclinical • Dengue Fever • Infectious Disease

Vitamin C Conjugates in Biomedicine: A Comprehensive Exploration with Drugs, Polymers, Proteins, and Peptides. (PubMed, Mini Rev Med Chem) - "Vitamin C-drug conjugates, including derivatives of diclofenac, aspirin, and naproxen, have demonstrated improved transport across the blood-brain barrier via SVCT-mediated uptake, offering potential for the treatment of neurodegenerative disorders. Similarly, conjugation with antivirals such as saquinavir improves oral absorption and systemic bioavailability by bypassing efflux mechanisms...Protein conjugates, utilizing carriers such as HSA, BSA, and β-lactoglobulin, facilitate systemic transport, while peptide conjugates leverage the antioxidant activity of vitamin C in conjunction with peptide-based targeting, providing synergistic benefits in cosmetics and dermatology. Collectively, these studies highlight vitamin C conjugation as a versatile platform for precision medicine and targeted therapy."

Journal • CNS Disorders • Dermatology • Oncology

Deciphering virus host interaction analysis to unravel core virus network signatures and computational drug repurposing for cervical cancer. (PubMed, Comput Biol Med) - "Ten candidate drugs, Pleconaril, Pirodavir, Saquinavir, Delavirdine, and Tipranavir for VE7_HPV16 and Beclabuvir, Velpatasvir, Paritaprevir, Odalasvir, and Ledipasvir for VE6_HPV18, were predicted to exhibit high binding affinities with their respective viral targets. Additionally, Molecular Dynamics (MD) simulations were performed to examine the stability of the protein-ligand complexes and evaluate the role of SLiMs-containing regions in modulating virus-host interactions. Collectively, this comprehensive analysis of the virus-host network identified key HPV protein targets and proposed antiviral drug candidates to impede viral contributions to cervical carcinogenesis."

Journal • Cervical Cancer • Infectious Disease • Oncology • Solid Tumor

Virtual screening of drugs against multiple targets of Alzheimer's disease. (PubMed, J Alzheimers Dis) - "BackgroundDrug repurposing offers a rapid, cost-effective approach for discovering therapies against multiple targets.ObjectiveHere, we screen virtual ligand libraries consisting of 3468 approved drugs against 11 protein targets associated with Alzheimer's disease (AD).MethodsWe employ blind molecular docking, and target amyloid-β (Aβ), microtubule-associated protein tau (MAPT), Apolipoprotein E4 (APOE4), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), amyloid-β protein precursor (AβPP), β-secretase (BACE1), brain-derived neurotrophic factor (BDNF), presenilin 1 (PSEN1) and 2 (PSEN2), and α-synuclein (SNCA) proteins using AutoDock Vina.ResultsNotably, multitarget binding recurs among the top-10 ligands with Ergotamine and Dihydroergotamine potentially binding 8; Dutasteride 7; Drospirenone and Nilotinib 6; Adapalene and Conivaptan 5; Bromocriptine 4; and Rolapitant, Irinotecan, Plerixafor, Saquinavir, and Telmisartan 3, out of 11 protein targets. Likewise,..."

Journal • Alzheimer's Disease • Cardiovascular • CNS Disorders • Hypertension • Inflammation • Pain • APOE • BDNF • MAPT • SNCA

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

Structure-based drug design; Computational strategies in drug discovery; Antihypertensive agents; Antiviral drugs; Molecular docking; QSAR; Pharmacological insights. (PubMed, Comput Biol Chem) - "This review meticulously examines the development, design, and pharmacological assessment of both well known antiviral and antihypertensive medications all time employing new chemical techniques and structure-based drug design to design and synthesize vital therapeutic entities such as aliskiren (renin inhibitor), captopril (a2-ACE-Inhibitor), dorzolamide (inhibitor of carbonic anhydrase) the review demonstrates initial steps regarding the significance of stereoselective synthesis, metal chelating pharmacophores, and rational molecular properties. More importantly, protease inhibitors (i.e., saquinavir, ritonavir, indinavir, amprenavir, etc.) and more contemporary agents (i.e., oseltamivir, nirmatrelvir/ritonavir (Paxlovid), etc.) were identified in the review and form a basis of advancement in antiviral therapy...In conclusion, this review highlights the transformative power of interdisciplinary approaches, including structure-based design, computational modeling, and..."

Journal • Review • Cardiovascular • Infectious Disease

Synthesis, Spectroscopic, Electronic and Molecular Docking Studies of Pyrazole Based Chalcones as Potential Anticancer Agents. (PubMed, J Fluoresc) - "Molecular docking against the 1B38 protease identified DF1 as the top binder (- 10.6 kcal/mol), outperforming the standard inhibitor Saquinavir (- 7.6 kcal/mol), via π-anion/cation interactions with Lys A:33 and Asp A:145, supported by ESP maps...Future work should prioritize in vitro validation and structural optimization to enhance selectivity and ADMET properties. This integrated approach highlights pyrazole-chalcones as promising anticancer scaffolds, with DF1 having superior binding and moderate toxicity warranting further development."

Journal • Oncology • CYP1A2

A computational effort to untangling anti-SARS-CoV-2 effects of oleanolic acid analogues. (PubMed, Pak J Pharm Sci) - "Through molecular docking and simulation studies, we found oleanolic acid (-12.6 Kcal/mol) and its two analogues (OA11; ligand I (-14.2 Kcal/mol)) and (OA31; ligand II (-14.0 Kcal/mol)) bound with Mpro (PDB: 6Y84) more reliable and trustful than saquinavir (-8.1 Kcal/mol) as a canonical drug. Salaspermic acid, (3b)-3-{[(2E)-3-phenylprop-2-enoyl]oxy}olean-12-en-28-oic acid, OA37 and OA40 interacted with catalytic dyad and major amino acid residues of active sites of Mpro and these toxic compounds should be considered in future anti-protease drug design. Overall, the current study seized the attention of experimentalists to the new set of anti-protease pentacyclic triterpenoids that should to be assayed against SARS-CoV-2 at in vitro or in clinical settings of COVID-19."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Computational design and evaluation of low-toxicity saquinavir analogues targeting the catalytic dyad and oxyanion-hole loop of SARS-CoV-2 Mpro: insights from ensemble docking, molecular dynamics, dynamic undocking, and ADMET analysis. (PubMed, Drug Chem Toxicol) - "Favorable ADMET profiles further support their potential as drug candidates with low mammalian toxicity. This study provides a strong foundation for experimental validation and the subsequent development of effective antiviral therapies against SARS-CoV-2."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

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

HIV protease inhibitors restore amphotericin B activity against Candida. (PubMed, PLoS One) - "In this study, we identified four HIV protease inhibitors (atazanavir, saquinavir, lopinavir and ritonavir) as strong potentiators of amphotericin B against C. auris. The in vivo treatment with HIV protease inhibitors combined with amphotericin B resulted in a significant reduction of C. auris colony-forming units (CFU) by 1.7-2.6 Log10 in the C. elegans model. These findings suggest that HIV protease inhibitors, in combination with amphotericin B, are promising candidates for the development of novel antifungal drugs to treat Candida infections."

Journal • Candidiasis • Human Immunodeficiency Virus • Infectious Disease