教員紹介 - 青木　学 | 熊本保健科学大学

アオキ　マナブ
青木　学

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保健科学部医学検査学科

保健科学研究科保健科学専攻

職種教授

著書・論文等
著書	臨床開発のパイプラインにある新規化合物医学のあゆみ 284 (9),719-725頁 (共著) 2023/03
論文	An orally available P1'-5-fluorinated Mpro inhibitor blocks SARS-CoV-2 replication without booster and exhibits high genetic barrier PNAS Nexus (共著) 2025/01
論文	Design, Synthesis, Evaluation and X-ray Structural Studies of Potent HIV-1 Protease Inhibitors Containing Substituted Oxaspirocyclic Carbamates as the P2 Ligands European Journal of Medicinal Chemistry,117880 (共著) 2025
論文	GRL-142 binds to and impairs HIV-1 integrase nuclear localization signal and potently suppresses highly INSTI-resistant HIV-1 variants Science Advances (共著) 2023/07/12
論文	Identification of SARS-CoV-2 Mpro inhibitors containing P1' 4-fluorobenzothiazole moiety highly active against SARS-CoV-2 Nature Communications (共著) 2023
論文	Design, Synthesis and X-Ray Structural Studies of Potent HIV-1 Protease Inhibitors Containing C-4 Substituted Tricyclic Hexahydro-Furofuran Derivatives as P2 Ligands. ChemMedChem (共著) 2022
論文	Single atom changes in newly synthesized HIV protease inhibitors reveal structural basis for extreme affinity, high genetic barrier, and adaptation to the HIV protease plasticity Scientific Reports 10 (1),10664 (共著) 2020
論文	Structure-based design of highly potent HIV-1 protease inhibitors containing new tricyclic ring P2-ligands: design, synthesis, biological, and X-ray structural studies Journal of medicinal chemistry 63 (9),4867-4879頁 (共著) 2020
論文	Synthesis and evaluation of the anti-hepatitis B virus activity of 4′-Azido-thymidine analogs and 4′-Azido-2′-deoxy-5-methylcytidine analogs: structural insights for the development of a novel anti-HBV agent Nucleosides, nucleotides & nucleic acids 39 (4),518-529頁 (共著) 2020
論文	A novel HIV-1 protease inhibitor, GRL-044, has potent activity against various HIV-1s with an extremely high genetic barrier to the emergence of HIV-1 drug resistance Global Health & Medicine 1 (1),36-48頁 (共著) 2019
論文	Halogen bond interactions of novel HIV-1 protease inhibitors (PI)(GRL-001-15 and GRL-003-15) with the flap of protease are critical for their potent activity against wild-type HIV-1 and multi-PI-resistant variants Antimicrobial Agents and Chemotherapy 63 (6),10.1128/aac. 02635-18 (共著) 2019
論文	Novel protease inhibitors containing C-5-modified bis-THF and aminobenzothiazole as P2 and P2' ligands that exert potent antiviral activity against highly multidrug-resistant HIV-1 with high genetic barrier against the emergence of drug resistance. Antimicrobial Agents and Chemotherapy 25 (63(8)),e00372--19頁 (共著) 2019
論文	Potent HIV-1 protease inhibitors incorporating squaramide-derived P2 ligands: Design, synthesis, and biological evaluation Bioorganic & medicinal chemistry letters 29 (18),2565-2570頁 (共著) 2019
論文	Potent HIV‐1 Protease Inhibitors Containing Carboxylic and Boronic Acids: Effect on Enzyme Inhibition and Antiviral Activity and Protein‐Ligand X‐ray Structural Studies ChemMedChem 14 (21),1863-1872頁 (共著) 2019
論文	Design and synthesis of highly potent HIV-1 protease inhibitors containing tricyclic fused ring systems as novel P2 ligands: structure–activity studies, biological and x-ray structural analysis Journal of medicinal chemistry 61 (10),4561-4577頁 (共著) 2018
論文	Design of Highly Potent, Dual‐Acting and Central‐Nervous‐System‐Penetrating HIV‐1 Protease Inhibitors with Excellent Potency against Multidrug‐Resistant HIV‐1 Variants ChemMedChem 13 (8),803-815頁 (共著) 2018
論文	GRL-079, a novel HIV-1 protease inhibitor, is extremely potent against multidrug-resistant HIV-1 variants and has a high genetic barrier against the emergence of resistant variants Antimicrobial Agents and Chemotherapy 62 (5),10.1128/aac. 02060-17 (共著) 2018
論文	Mechanism of darunavir (DRV)’s high genetic barrier to HIV-1 resistance: a key V32I substitution in protease rarely occurs, but once it occurs, it predisposes HIV-1 to develop DRV resistance MBio 9 (2),10.1128/mbio. 02425-17 (共著) 2018
論文	Raltegravir blocks the infectivity of red-fluorescent-protein (mCherry)-labeled HIV-1JR-FL in the setting of post-exposure prophylaxis in NOD/SCID/Jak3−/− mice transplanted with human PBMCs Antiviral research 149,78-88頁 (共著) 2018
論文	Synthesis of 4′‐Substituted Purine 2′‐Deoxynucleosides and Their Activity against Human Immunodeficiency Virus Type 1 and Hepatitis B Virus ChemistrySelect 3 (11),3313-3317頁 (共著) 2018
論文	Synthesis of 4о-Substituted Purine 2о-Deoxynucleosides and Their Activity against Human Immunodeficiency Virus Type 1 and Hepatitis B Virus (共著) 2018
論文	A novel central nervous system-penetrating protease inhibitor overcomes human immunodeficiency virus 1 resistance with unprecedented aM to pM potency Elife 6,e28020 (共著) 2017
論文	Design and development of highly potent HIV-1 protease inhibitors with a crown-like oxotricyclic core as the P2-ligand to combat multidrug-resistant HIV variants Journal of medicinal chemistry 60 (10),4267-4278頁 (共著) 2017
論文	Design of novel HIV-1 protease inhibitors incorporating isophthalamide-derived P2-P3 ligands: Synthesis, biological evaluation and X-ray structural studies of inhibitor-HIV-1 protease complex Bioorganic & medicinal chemistry 25 (19),5114-5127頁 (共著) 2017
論文	Design, Synthesis, Biological Evaluation, and X‐ray Studies of HIV‐1 Protease Inhibitors with Modified P2′ Ligands of Darunavir ChemMedChem 12 (23),1942-1952頁 (共著) 2017
論文	Design, synthesis, X-ray studies, and biological evaluation of novel macrocyclic HIV-1 protease inhibitors involving the P1′-P2′ ligands Bioorganic & medicinal chemistry letters 27 (21),4925-4931頁 (共著) 2017
論文	Early phase dynamics of traceable mCherry fluorescent protein-carrying HIV-1 infection in human peripheral blood mononuclear cells-transplanted NOD/SCID/Jak3-/-mice Antiviral research 144,83-92頁 (共著) 2017
論文	C-5-modified tetrahydropyrano-tetrahydofuran-derived protease inhibitors (PIs) exert potent inhibition of the replication of HIV-1 variants highly resistant to various PIs, including darunavir Journal of virology 90 (5),2180-2194頁 (共著) 2016
論文	Diastereoselective synthesis of 6 ″-(Z)-and 6 ″-(E)-fluoro analogues of anti-hepatitis B virus agent entecavir and its evaluation of the activity and toxicity profile of the diastereomers The Journal of organic chemistry 81 (7),2827--2836頁 (共著) 2016
論文	Human neutrophil elastase induce interleukin-10 expression in peripheral blood mononuclear cells through protein kinase C theta/delta and phospholipase pathways Cell Journal (Yakhteh) 17 (4),692 (共著) 2016
論文	Probing lipophilic adamantyl group as the P1-ligand for HIV-1 protease inhibitors: design, synthesis, protein X-ray structural studies, and biological evaluation Journal of medicinal chemistry 59 (14),6826-6837頁 (共著) 2016
論文	4'‐modified nucleoside analogs: Potent inhibitors active against entecavir‐resistant hepatitis B virus Hepatology 62 (4),1024-1036頁 (共著) 2015
論文	C-5-Modified Tetrahydropyrano-Tetrahydofuran-Derived Protease Inhibitors (PIs) Exert Potent Inhibition of the Replication of HIV-1 Variants Highly Resistant to Various PIs, including Darunavir. Jornal of Virology 18 (90(5)),01829--15頁 (共著) 2015
論文	Design of gem‐Difluoro‐bis‐Tetrahydrofuran as P2 Ligand for HIV‐1 Protease Inhibitors to Improve Brain Penetration: Synthesis, X‐ray Studies, and Biological Evaluation ChemMedChem 10 (1),107-115頁 (共著) 2015
論文	Design of HIV-1 Protease Inhibitors with Amino-bis-tetrahydrofuran Derivatives as P2-Ligands to Enhance Backbone-Binding Interactions: Synthesis, Biological Evaluation, and Protein–Ligand X-ray Studies Journal of medicinal chemistry 58 (17),6994--7006頁 (共著) 2015
論文	Design, synthesis, and evaluation of anti-HBV activity of hybrid molecules of entecavir and adefovir: exomethylene acycloguanine nucleosides and their monophosphate derivatives Nucleosides, Nucleotides and Nucleic Acids 34 (8),590-602頁 (共著) 2015
論文	Granulocyte–macrophage colony-stimulating factor primes interleukin-13 production by macrophages via protease-activated receptor-2 Blood Cells, Molecules, and Diseases 54 (4),353-359頁 (共著) 2015
論文	Mechanism of tissue factor production by monocytes stimulated with neutrophil elastase Blood Cells, Molecules, and Diseases 54 (2),206-209頁 (共著) 2015
論文	Structure-based design, synthesis, X-ray studies, and biological evaluation of novel HIV-1 protease inhibitors containing isophthalamide-derived P2-ligands Bioorganic & medicinal chemistry letters 25 (21),4903-4909頁 (共著) 2015
論文	A conserved hydrogen-bonding network of P2 bis-tetrahydrofuran-containing HIV-1 protease inhibitors (PIs) with a protease active-site amino acid backbone aids in their activity against PI-resistant HIV Antimicrobial agents and chemotherapy 58 (7),3679-3688頁 (共著) 2014
論文	Delayed emergence of HIV-1 variants resistant to 4′-ethy nyl-2-fluoro-2′-deoxyadenosine: comparative sequential passage study with lamivudine, tenofovir, emtricitabine and BMS-986001 Antiviral therapy 19 (2),179-189頁 (共著) 2014
論文	Dimerization of HIV-1 protease occurs through two steps relating to the mechanism of protease dimerization inhibition by darunavir Proceedings of the National Academy of Sciences 111 (33),12234-12239頁 (共著) 2014
論文	HIV のプロテアーゼ阻害剤（PI）耐性獲得機構の解析と新規 PI 開発への応用日本エイズ学会誌,77-83頁 (単著) 2014
論文	GRL-0519, a novel oxatricyclic ligand-containing nonpeptidic HIV-1 protease inhibitor (PI), potently suppresses replication of a wide spectrum of multi-PI-resistant HIV-1 variants in vitro Antimicrobial agents and chemotherapy 57 (5),2036-2046頁 (共著) 2013
論文	P2' benzene carboxylic acid moiety is associated with decrease in cellular uptake: evaluation of novel nonpeptidic HIV-1 protease inhibitors containing P2 bis-tetrahydrofuran moiety Antimicrobial agents and chemotherapy 57 (10),4920-4927頁 (共著) 2013
論文	Loss of the protease dimerization inhibition activity of tipranavir (TPV) and its association with the acquisition of resistance to TPV by HIV-1 Journal of virology 86 (24),13384-13396頁 (共著) 2012
論文	Loss of protease dimerization inhibition activity of darunavir is associated with the acquisition of resistance to darunavir by HIV-1 Journal of virology 85 (19),10079-10089頁 (共著) 2011
論文	Novel HIV-1 protease inhibitors (PIs) containing a bicyclic P2 functional moiety, tetrahydropyrano-tetrahydrofuran, that are potent against multi-PI-resistant HIV-1 variants Antimicrobial agents and chemotherapy 55 (4),1717-1727頁 (共著) 2011
論文	Novel protease inhibitors (PIs) containing macrocyclic components and 3 (R), 3a (S), 6a (R)-bis-tetrahydrofuranylurethane that are potent against multi-PI-resistant HIV-1 variants in vitro Antimicrobial agents and chemotherapy 54 (8),3460-3470頁 (共著) 2010
論文	Probing multidrug-resistance/protein-ligand interaction with oxatricyclic designed ligands in HIV-1 Protease inhibitors ChemMedChem 5 (11),1850 (共著) 2010
論文	Non-cleavage site gag mutations in amprenavir-resistant human immunodeficiency virus type 1 (HIV-1) predispose HIV-1 to rapid acquisition of amprenavir resistance but delay development of resistance to other protease inhibitors Journal of virology 83 (7),3059-3068頁 (共著) 2009
論文	Reduction of peptide character of HIV protease inhibitors that exhibit nanomolar potency against multidrug resistant HIV-1 strains Journal of medicinal chemistry 46 (9),1764-1768頁 (共著) 2003
論文	The impact of highly active antiretroviral therapy by the oral route on the CD8 subset in monkeys infected chronically with SHIV89. 6P Journal of virological methods 112 (45659),121-128頁 (共著) 2003
論文	Genetic evidence of transmission of human T cell lymphotropic virus type 1 between spouses The Journal of infectious diseases 185 (5),691-695頁 (共著) 2002
論文	Missense mutation of the interleukin-12 receptor β1 chain–encoding gene is associated with impaired immunity against Mycobacterium avium complex infection Blood, The Journal of the American Society of Hematology 97 (9),2688-2694頁 (共著) 2001
論文	Novel low molecular weight spirodiketopiperazine derivatives potently inhibit R5 HIV-1 infection through their antagonistic effects on CCR5 Journal of Biological Chemistry 276 (37),35194-35200頁 (共著) 2001