2017
From in silico hit to long-acting late-stage preclinical candidate to combat HIV-1 infection
Kudalkar SN, Beloor J, Quijano E, Spasov KA, Lee WG, Cisneros JA, Saltzman WM, Kumar P, Jorgensen WL, Anderson KS. From in silico hit to long-acting late-stage preclinical candidate to combat HIV-1 infection. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 115: e802-e811. PMID: 29279368, PMCID: PMC5789948, DOI: 10.1073/pnas.1717932115.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnti-HIV AgentsComputer SimulationDisease Models, AnimalDrug Delivery SystemsDrug Evaluation, PreclinicalDrug SynergismHIV InfectionsHIV-1MiceMice, Inbred BALB CNanoparticlesConceptsHIV-1 drugsDrug-resistant HIV-1 strainsHIV-1 drug-resistant strainsPreclinical candidateDrug-resistant HIV-1HIV-1-infected T cellsDaily treatment regimensActive antiretroviral therapyT cell lossSynergistic antiviral activityHIV-1 infectionAnti-HIV-1 agentsCombination drug regimensHIV-1 strainsMajor therapeutic challengeHIV-1 pandemicPlasma drug concentrationsDrug-resistant strainsVivo pharmacokinetic behaviorAntiretroviral therapyDrug regimensTherapeutic challengeViral loadTreatment regimensSingle doseStructural and Preclinical Studies of Computationally-Designed Non-nucleoside Reverse Transcriptase Inhibitors for Treating HIV infection
Kudalkar SN, Beloor J, Chan AH, Lee WG, Jorgensen WL, Kumar P, Anderson KS. Structural and Preclinical Studies of Computationally-Designed Non-nucleoside Reverse Transcriptase Inhibitors for Treating HIV infection. Molecular Pharmacology 2017, 91: mol.116.107755. PMID: 28167742, PMCID: PMC5363707, DOI: 10.1124/mol.116.107755.Peer-Reviewed Original ResearchConceptsNon-nucleoside reverse transcriptase inhibitorBALB/c miceReverse transcriptase inhibitorHIV infectionC miceTranscriptase inhibitorAntiviral activityCompound INew non-nucleoside reverse transcriptase inhibitorHIV-1 non-nucleoside reverse transcriptase inhibitorDetectable acute toxicityTreating HIV InfectionSingle intraperitoneal doseAnti-HIV-1 potencyMT-2 cellsDrug-resistant variantsCompound IISerum residence timeAnti-viral potencyHIV-1 RTClinical benefitClinical efficacyIntraperitoneal doseWild-type HIV-1 RTPlasma clearance
2013
Virtual screening reveals allosteric inhibitors of the Toxoplasma gondii thymidylate synthase–dihydrofolate reductase
Sharma H, Landau MJ, Sullivan TJ, Kumar VP, Dahlgren MK, Jorgensen WL, Anderson KS. Virtual screening reveals allosteric inhibitors of the Toxoplasma gondii thymidylate synthase–dihydrofolate reductase. Bioorganic & Medicinal Chemistry Letters 2013, 24: 1232-1235. PMID: 24440298, PMCID: PMC3946055, DOI: 10.1016/j.bmcl.2013.12.039.Peer-Reviewed Original ResearchConceptsThymidylate synthase-dihydrofolate reductaseSynthase-dihydrofolate reductaseVirtual screeningSmall drug-like moleculesAllosteric inhibitorsDrug-like moleculesSpecies-specific inhibitorsNovel allosteric inhibitorsSuitable drug targetsTS domainParasite Toxoplasma gondiiAllosteric inhibitionDrug targetsTS activityReductaseToxoplasma gondiiInhibitorsCompoundsMoleculesEnzymeScreening
2009
Discovery of Wild-Type and Y181C Mutant Non-nucleoside HIV-1 Reverse Transcriptase Inhibitors Using Virtual Screening with Multiple Protein Structures
Nichols SE, Domaoal RA, Thakur VV, Tirado-Rives J, Anderson KS, Jorgensen WL. Discovery of Wild-Type and Y181C Mutant Non-nucleoside HIV-1 Reverse Transcriptase Inhibitors Using Virtual Screening with Multiple Protein Structures. Journal Of Chemical Information And Modeling 2009, 49: 1272-1279. PMID: 19374380, PMCID: PMC2817966, DOI: 10.1021/ci900068k.Peer-Reviewed Original ResearchMeSH KeywordsDrug DesignDrug Evaluation, PreclinicalModels, MolecularReverse Transcriptase InhibitorsConceptsNon-nucleoside HIV-1 reverse transcriptase inhibitorReverse transcriptase inhibitorHIV-1 reverse transcriptaseHIV-1 Reverse Transcriptase InhibitorsTranscriptase inhibitorHIV-1RT mutationsNon-nucleoside inhibitorsAntiviral activityHIV agentsWild-type virusResistance profilesWT virusReverse transcriptaseInhibitorsScreeningVirtual screening