amprenavir / Generic mfg. - LARVOL DELTA

Engineered Virus-like Particles with Minimal Viral Components for Improved Base Editing Efficiency in vivo (ASGCT 2025) - "The introduction of Amprenavir, an HIV protease inhibitor, during Gag-Pro particle production resulted in up to a 5-fold increase in particle Cas9 content relative to untreated Gag-Pro controls and a dramatic increase in editing efficiency of HEK293T cells...The increased production efficiency and cargo loading/release resulting from the design and process changes described above, in addition to the improved safety profile, enable exploration of the full potential of DLVR-X as a therapeutic protein delivery platform. Disease Focus of Abstract:None"

Preclinical • Hematological Malignancies • Human Immunodeficiency Virus • Infectious Disease • Leukemia • Oncology

Insights into the interaction mechanism of first-generation HIV-1 protease inhibitors with wild-type and mutant (D30N and L76V) enzymes through in-silico based approach. (PubMed, J Biomol Struct Dyn) - "The present study focuses on to understand the alterations in wild-type and mutants (D30N and L76V) PR structure by interaction of first-generation PR inhibitors amprenavir, indinavir, nelfinavir, ritonavir and saquinavir. L76V mutant does not form any direct interaction with the first line drugs; hence the drugs forming strong interactions with the active site, flap domain and substrate binding region residues are quite enough to manage the resistance provided by L76V mutant. The results provided the insight into the drug-resistant or drug-susceptibility mechanism of L76V and D30N mutation against first-generation PR inhibitors."

Journal • Human Immunodeficiency Virus • Infectious Disease

Ritonavir enhances the efficacy of amprenavir: a promising combination therapy by targeting Leishmania DNA Topoisomerase I for treatment of visceral leishmaniasis HIV-VL co-infection. (PubMed, Exp Parasitol) - "From the in vitro, ex vivo and in vivo studies, it was indicated that lower dose of APV in lower dose in combination with RTV elevated the effective killing of the parasites as compared to the single higher dose of APV. Thus, the current study highlights repurposing of available protease inhibitors in combination, which might be exploited further for the therapeutic development against VL as well as HIV-VL co-infection."

Journal • Human Immunodeficiency Virus • Infectious Disease • TOP1

PRIMARY HUMAN ORAL EPITHELIUM TREATED WITH ANTI-HIV PROTEASE INHIBITOR IDENTIFIES HOST GENES AND SIGNALING PATHWAYS THAT FAVOR HPV16 INFECTION AND DE NOVO VIRION BIOSYNTHESIS (IPVC 2024) - " In the current study, we performed microarray analysis to determine expression of host genes and pathways that are differentially modulated by Amprenavir treatment that potentially support HPV16 infection and viral life cycle. Amprenavir treatment of primary gingiva rafts showed upregulated gene expression profiles associated with mitochondrial metabolism and oxidative stress that link with pathways known to regulate HPV functions... Changes in subsequent viral load could promote new infections, increase virus persistence, and the risk of developing oral cancers in HIV-positive patients undergoing long-term HAART treatment."

Head and Neck Cancer • Human Immunodeficiency Virus • Human Papillomavirus Infection • Infectious Disease • Oncology • Oral Cancer • Solid Tumor • CDK1 • CDK2 • CDKN1A

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."

Adverse events • Checkpoint inhibition • Journal • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Arthritis • Inflammatory Bowel Disease • Melanoma • Oncology • Rheumatoid Arthritis • Rheumatology • Solid Tumor • Ulcerative Colitis • IL6 • IL6R • PD-1 • PD-L1

Identification of steroidal cardenolides from Calotropis procera as novel HIV-1 PR inhibitors: A molecular docking & molecular dynamics simulation study. (PubMed, Indian J Med Res) - "Results We found that all tested cardenolides had higher binding affinities than Amprenavir, indicating their potential as potent HIV-1 PR inhibitors...Interpretation & conclusions These findings suggest that Calotropis procera could potentially be a source of compounds for developing novel HIV-1 PR inhibitors, contributing to the efforts to combat HIV. Further studies and clinical trials are needed to evaluate the safety and efficacy of these compounds as potential drug candidates for the treatment of HIV-1 infection."

Journal • Human Immunodeficiency Virus • Infectious Disease

In Silico Drug Repurposing Endorse Amprenavir, Darunavir and Saquinavir to Target Enzymes of Multidrug Resistant Uropathogenic E. Coli. (PubMed, Indian J Microbiol) - "Combination or sole application of Amprenavir, Darunavir and Saquinavir to MDR-UPEC infections may leads to cure and inhibition of mortality. The online version contains supplementary material available at 10.1007/s12088-024-01282-x."

Journal • Human Immunodeficiency Virus • Infectious Disease

Development and validation of an LC-MSMS method for the quantitation of pacritinib; application of kinetics in rabbits. (PubMed, J Pharmacol Toxicol Methods) - "After oral administration of Pacritinib to healthy rabbits, pharmacokinetic characteristics were presented, and the established technique was effectively verified."

Journal • Preclinical • Myelofibrosis

Anti-HIV Activity and Immunomodulatory Properties of Fractionated Crude Extracts of Alternaria alternata. (PubMed, Microorganisms) - "These included maraviroc, azidothymidine, raltegravir, and amprenavir. A. alternata could be a key source of innovative anti-HIV drugs with immunomodulatory characteristics."

Immunomodulating • IO biomarker • Journal • Human Immunodeficiency Virus • Infectious Disease • Targeted Protein Degradation • CD4 • PD-1

Molecular modeling of some commercially available antiviral drugs and their derivatives against SARS-CoV-2 infection. (PubMed, Narra J) - "In parallel, antiviral compounds like abacavir, acyclovir, adefovir, amantadine, amprenavir, darunavir, didanosine, oseltamivir, penciclovir, and tenofovir are under investigation for their potential in drug repurposing to address this infection. Moreover, NCH3 derivative of abacavir (-6.506 kJ/mol), NO2 derivative of didanosine (-6.877 kJ/mol), NCH3 derivative of darunavir (-7.618 kJ/mol) exerted promising affinity to Mpro. In conclusion, the results of the in silico screenings can serve as a useful information for future experimental works."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Molecular Docking Improved With Human Spatial Perception Using Virtual Reality. (PubMed, IEEE Trans Vis Comput Graph) - "We also explain the benefits of using VR as a tool for expediting the process of ligand binding, outlining an experimental protocol that enables iMD-VR users to guide Amprenavir into and out of the binding pockets of HIV-1 protease and recreate their respective crystallographic binding poses within 5 minutes...Finally, we describe the novelty of the research and discuss results showcasing a faster and more effective convergence of the ligand to the protein's binding site as compared to a standard molecular dynamics simulation, proving the effectiveness of VR in the field of drug discovery. Future work includes the development of an artificial intelligence algorithm capable of predicting optimal binding trajectories for many protein-ligand pairs, as well as the required force needed to steer the ligand to follow the said trajectory."

Journal • Human Immunodeficiency Virus • Infectious Disease

Amprenavir inhibits pepsin-mediated laryngeal epithelial disruption and E-cadherin cleavage in vitro. (PubMed, Laryngoscope Investig Otolaryngol) - "Amprenavir, at serum concentrations achievable provided the manufacturer's recommended dose of fosamprenavir for HIV, protects against pepsin-mediated cell dissociation, E-cadherin cleavage, and MMP dysregulation thought to contribute to barrier dysfunction and related symptoms during LPR. Fosamprenavir to amprenavir conversion by laryngeal epithelia, serum and saliva, and relative drug efficacies in an LPR mouse model are under investigation to inform development of inhaled formulations for LPR."

Journal • Preclinical • Chronic Cough • Cough • Gastroesophageal Reflux Disease • Gastrointestinal Disorder • Human Immunodeficiency Virus • Infectious Disease • Oncology • Otorhinolaryngology • Pulmonary Disease • Respiratory Diseases • Targeted Protein Degradation • CDH1 • MMP1

Development of a novel fluorogenic assay method for screening inhibitors of bovine leukemia virus (BLV) protease and identification of mitorubrinic acid as an anti-BLV compound. (PubMed, Biosci Biotechnol Biochem) - "The developed assay method was used to screen a chemical library, and mitorubrinic acid was identified as a BLV protease inhibitor that exhibited stronger inhibitory activity than amprenavir...This study presents the first report of a natural inhibitor of BLV protease-mitorubrinic acid-a potential candidate for the development of anti-BLV drugs. The developed method can be used for high-throughput screening of large-scale chemical libraries."

Journal • Hematological Malignancies • Leukemia • Oncology

The Protease Inhibitor Amprenavir Protects against Pepsin-Induced Esophageal Epithelial Barrier Disruption and Cancer-Associated Changes. (PubMed, Int J Mol Sci) - "Amprenavir, at serum concentrations achievable given the manufacturer-recommended dose of fosamprenavir, protected against pepsin-induced cell dissociation, E-cadherin cleavage, and MMP induction. These results support a potential therapeutic role for amprenavir in GERD recalcitrant to PPI therapy and for preventing GERD-associated neoplastic changes."

Journal • Barrett Esophagus • Esophageal Adenocarcinoma • Esophageal Cancer • Gastroenterology • Gastroesophageal Reflux Disease • Gastrointestinal Cancer • Gastrointestinal Disorder • Human Immunodeficiency Virus • Infectious Disease • Oncology • Solid Tumor • Targeted Protein Degradation • CDH1

Vitamin E TPGS-Based Nanomedicine, Nanotheranostics, and Targeted Drug Delivery: Past, Present, and Future. (PubMed, Pharmaceutics) - "Since then, four drugs with TPGS in their formulation have been approved for sale in the United States and Europe including ibuprofen, tipranavir, amprenavir, and tocophersolan...Docetaxel, paclitaxel, and doxorubicin are examples of poorly bioavailable therapeutic agents; hence, much effort is applied for developing TPGS-based nanomedicine, nanotheranostics, and targeted drug delivery systems to increase circulation time and promote the reticular endothelial escape of these drug delivery systems...However, various randomized or human clinical trials have been underway for TPGS-based drug delivery systems for multiple diseases such as pneumonia, malaria, ocular disease, keratoconus, etc. In this review, we have emphasized in detail the review of the nanotheranostics and targeted drug delivery approaches premised on TPGS. In addition, we have covered various therapeutic systems involving TPGS and its analogs with special references to its patent and clinical trials."

Journal • Review • Infectious Disease • Malaria • Oncology • Ophthalmology • Pneumonia • Respiratory Diseases

Understanding the impact of halogen functional group (Br, Cl, F, OH) in amprenavir ligand of the HIV protease. (PubMed, J Biomol Struct Dyn) - "The present work will reveal an understandable picture about the halogen and hydrogen bond interaction that grip the contact of ligand and amino acids in the hinge region. Overall the Halogen atom (Br, Cl, F) functional groups improved the binding strength of APV in HIV protease; which provide a new novel path for the functional group preference on the ligand that enclose perfectly with the amino acid in the hinge region.Communicated by Ramaswamy H. Sarma."

Journal • Human Immunodeficiency Virus • Immunology • Infectious Disease

Decoding drug resistant mechanism of V32I, I50V and I84V mutations of HIV-1 protease on amprenavir binding by using molecular dynamics simulations and MM-GBSA calculations. (PubMed, SAR QSAR Environ Res) - "Thus, the conformational changes of two flaps in the PR caused by V32I, I50V and I84V play key roles in drug resistance of three mutated PR towards APV. This study can provide useful dynamics information for the design of potent inhibitors relieving drug resistance."

Journal • Human Immunodeficiency Virus • Infectious Disease

In silico analysis of SARS-CoV-2 proteins as targets for clinically available drugs. (PubMed, Sci Rep) - "Three drugs-amprenavir, levomefolic acid, and calcipotriol-were predicted to bind to 3 different sites on the spike protein, domperidone to the Mac1 domain of the non-structural protein (Nsp) 3, avanafil to Nsp15, and nintedanib to the nucleocapsid protein involved in packaging the viral RNA. Our "two-way" virtual docking screen also provides a framework to prioritize drugs for testing in future emergencies requiring rapidly available clinical drugs and/or treating diseases where a moderate number of targets are known."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Pharmacokinetic Outcomes of the Interactions of Antiretroviral Agents with Food and Supplements: A Systematic Review and Meta-Analysis. (PubMed, Nutrients) - "Food-drug coadministration significantly increased the time to reach maximum concentration (t) (p < 0.00001) of ARV including abacavir, amprenavir, darunavir, emtricitabine, lamivudine, zidovudine, ritonavir, and tenofovir alafenamide. Evaluating the pharmacokinetic aspects, it is vital to clinically investigate ARV and particular supplement interaction in PLWH. Educating patients about any potential interactions would be one of the effective recommendations during this HIV epidemic."

Journal • PK/PD data • Retrospective data • Review • Human Immunodeficiency Virus • Immunology • Infectious Disease

Novel Real-Time Library Search Driven Data Acquisition Strategy for Identification and Characterization of Metabolites. (PubMed, Anal Chem) - "We applied this strategy to an Amprenavir sample incubated with human liver microsomes...Furthermore, the MS fragments were selected to focus likely sources of useful structural information, specifically higher mass fragments to maximize acquisition of MS data relevant for structure assignment. The described Met-IQ strategy is not limited to metabolism experiments and can be applied to analytical samples where the detection of unknown compounds structurally related to a known compound(s) is sought."

Journal

Fluorine-Modifications Contribute to Potent Antiviral Activity against Highly Drug-Resistant HIV-1 and Favorable Blood-Brain Barrier (BBB) Penetration Property of Novel Central Nervous System (CNS)-targeting HIV-1 Protease Inhibitors In Vitro. (PubMed, Antimicrob Agents Chemother) - "As assessed with HIV-1 variants that had been selected in vitro to propagate at 5 μM concentration of each HIV-1 PI (atazanavir, lopinavir, or amprenavir), GRL-08513 and GRL-08613 efficiently inhibited the replication of these highly-PI-resistant variants (EC: 0.003∼0.006 μM). Furthermore, both the P1-3,5-bis-fluorophenyl- and P1-para-monofluorophenyl-rings sustain greater contact surfaces and form stronger van der Waals interactions with PR compared to the case of darunavir-PR complex. Taken together, these results strongly suggest that GRL-08513 and GRL-08613 have favorable features for the patients infected with wild-type/multi-drug-resistant HIV-1s, and might serve as candidates of preventive and/or therapeutic for HAND and other CNS complications."

Journal • Preclinical • CNS Disorders • Cognitive Disorders • Developmental Disorders • Human Immunodeficiency Virus • Infectious Disease

Repurposing drug molecule against SARS-Cov-2 (COVID-19) through molecular docking and dynamics: a quick approach to pick FDA-approved drugs. (PubMed, J Mol Model) - "Using well-defined computational methods, we identified amprenavir, cefoperazone, riboflavin, diosmin, nadide and troxerutin approved for human therapeutic uses, as COVID-19 main protease inhibitors...We have found diosmin as an inhibitor which binds covalently to the COVID-19 main protease. This study provides enough evidences for therapeutic use of these drugs in controlling COVID-19 after experimental validation and clinical demonstration."

FDA event • Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Revertant mutation V48G alters conformational dynamics of highly drug resistant HIV protease PRS17. (PubMed, J Mol Graph Model) - "Clinical inhibitors, amprenavir and darunavir, showed 2-fold and 8-fold better inhibition, respectively, of the revertant than of PRS17, although the inhibition constants for PRS17 were still 25 to 1,200-fold worse than for wild-type protease. The second half of the simulations captured the transition of the flaps of PRS17 from a closed to a semi-open state, whereas the flaps of PRS17 tucked into the active site and the wild-type protease retained the closed conformation. These results suggest that mutation G48V contributes to drug resistance by altering the conformational dynamics of the flaps."

Journal • Human Immunodeficiency Virus • Infectious Disease

Predicted antiviral drugs Darunavir, Amprenavir, Rimantadine and Saquinavir can potentially bind to neutralize SARS-CoV-2 conserved proteins. (PubMed, J Biol Res (Thessalon)) - " Repurposing of the antiviral drugs Darunavir, Amprenavir, Rimantadine and Saquinavir to treat COVID-19 patients could be useful that can potentially prevent human mortality."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Insights into effect of the Asp25/Asp25' protonation states on binding of inhibitors Amprenavir and MKP97 to HIV-1 protease using molecular dynamics simulations and MM-GBSA calculations. (PubMed, SAR QSAR Environ Res) - "Calculations of residue-based free energy decomposition indicate that the Asp25/Asp25' protonation not only disturbs the interaction network of inhibitors with PR but also stabilizes bindings of inhibitors to PR by cancelling the electrostatic repulsive interaction. Therefore, special attentions should be paid to the Asp25/Asp25' protonation in the design of potent inhibitors towards PR."

Journal • Human Immunodeficiency Virus • Infectious Disease