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Drug Discovery Case History

The preclinical discovery and development of dolutegravir for the treatment of HIV

(Faculty of Pharmaceutical and Biological Sciences) & (Faculty of Pharmaceutical and Biological Sciences)

Bibliography

  • Maurin C, Bailly F, Cotelle P. Structure-activity relationships of HIV-1 integrase inhibitors: Enzyme-ligand interactions. Curr Med Chem 2003;10:1795-810
  • Hazuda DJ, Felock P, Witmer M, et al. Inhibitors of strand transfer that prevent integration and inhibit HIV-1 replication in cells. Science 2000;287:646-50
  • Japan Tobacco Inc. Preparation of 4-oxoquinoline derivatives as HIV integrase inhibitors. WO2004046115 A1; 2004
  • Sato M, Motomura T, Aramaki H, et al. Novel HIV-1 integrase inhibitors derived from quinolone antibiotics. J Med Chem 2006;49:1506-8
  • Shionogi Pharmaceuticals. Preparation of indole derivatives with antiviral activity. WO09950245; 1999
  • Shionogi Pharmaceuticals. Polycyclic carbamoylpyridone derivative having HIV integrase inhibitory activity. WO2006116764 A1; 2006
  • GSK. Tricyclic heterocyclic compounds as antiviral agents and their preparation and use in the treatment of HIV infection. WO2010011812 A1; 2010
  • GSK. Tricyclic heterocyclic compounds as antiviral agents and their preparation and use in the treatment of HIV infection. WO2010011819 A1; 2010
  • Kawasuji T, Johns BA, Yoshida H, et al. Carbamoyl Pyridone HIV-1 integrase inhibitors. 1. Molecular design and establishment of an advanced two-metal binding pharmacophore. J Med Chem 2012;55:8735-44
  • Kawasuji T, Johns BA, Yoshida H, et al. Carbamoyl Pyridone HIV-1 integrase inhibitors. 2. Bi- and tricyclic derivatives result in superior antiviral and pharmacokinetic profiles. J Med Chem 2013;56:1124-35
  • Johns BA, Kawasuji T, Weatherhead JG, et al. Carbamoyl Pyridone HIV-1 Integrase Inhibitors 3. A diastereomeric approach to chiral nonracemic tricyclic ring systems and the discovery of dolutegravir (S/GSK1349572) and (S/GSK1265744). J Med Chem 2013;56:5901-16
  • Lennox JL, DeJesus E, Lazzarin A, et al. Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-I patients with HIV-1 infection: a multicentre, double-blind randomised controlled trial. Lancet 2009;374:796-806
  • Ceccherini-Silberstein F, Malet I, D’Arrigo R, et al. Characterization and structural analysis of HIV-1 integrase conservation. AIDS Rev 2009;11:17-29
  • Johnson VA, Brun-Vezinet F, Clotet B, et al. Update of the drug resistance mutations in HIV-1. Top HIV Med 2010;18:156-63
  • Wainberg MA, Mesplède T, Quashie PK. The development of novel HIV integrase inhibitors and the problem of drug resistance. Curr Opin Virol 2012;2:656-62
  • Ramanathan S, Mathias AA, German P, Kearney BP. Clinical pharmacokinetic and pharmacodynamics profile of the HIV integrase inhibitor elvitegravir. Clin Pharmacokinet 2011;50:229-44
  • Serrao E, Odde S, Ramkumar K, Neamati N. Raltegravir, elvitegravir, and metoogravir: the birth of “me-too” HIV-1 integrase inhibitors. Retrovirology 2009;6:25
  • Wai JS, Egbertson MS, Payne LS, et al. 4-Aryl-2,4-dioxobutanoic acid inhibitors of HIV-1 integrase and viral replication in cells. J Med Chem 2000;43:4923-6
  • Hare S, Gupta SS, Volkov E, et al. Retroviral intasome assembly and inhibition of DNA strand transfer. Nature 2010;464:232-6
  • Grobler JA, Stillmock K, Binghua H, et al. Diketo acid inhibitor mechanism and integrase: implications for metal binding in the active site of phosphotransferase enzymes. Proc Natl Acad Sci USA 2002;99:6661-6
  • Maurin C, Bailly F, Buisine E, et al. Spectroscopic studies of diketoacids-metal interactions. A probing tool for the pharmacophoric intermetallic distance in the HIV-1 integrase active site. J Med Chem 2004;47:5583-6
  • Sechi M, Bacchi A, Carcelli M, et al. From ligand to complexes: inhibition of human immunodeficiency virus type 1 integrase by beta-diketo acid metal complexes. J Med Chem 2006;49:4248-60
  • Bacchi A, Biemmi M, Carcelli M, et al. From ligand to complexes. Part 2. Remarks on human immunodeficiency virus type 1 integrase inhibition by betadiketo acid metal complexes. J Med Chem 2008;51:7253-64
  • Billamboz M, Bailly F, Lion C, et al. Magnesium chelating 2-hydroxyisoquinoline-1,3-(2H,4H)-diones as inhibitors of HIV-1 integrase and/or the HIV-1 reverse transcriptase ribonuclease H domain: discovery of a novel selective inhibitor of the ribonuclease H function. J Med Chem 2011;54:1812-24
  • Desimmie BA, Demeulemeester J, Suchaud V, et al. 2-Hydroxyisoquinoline-1,3(2H,4H)-diones (HIDs), novel inhibitors of HIV integrase with a high barrier to resistance. ACS Chem Biol 2013;8:1187-94
  • Pasquini S, Mugnaini C, Tintori C, et al. Investigations on the 4-quinolone-3-carboxylic acid motif. 1. Synthesis and structure-activity relationship of a class of human immunodeficiency virus type 1 integrase inhibitors. J Med Chem 2008;51:5125-9
  • Eron JJ, Clotet B, Durant J, et al. Safety and efficacy of dolutegravir in treatment experienced subjects with raltegravir resistant HIV type 1 infection: 24-week results of the VIKING Study. J Infect Dis 2013;207:740-8
  • Kobayashi M, Yoshinaga T, Seki T, et al. In Vitro antiretroviral properties of S/GSK1349572, a next-generation HIV integrase inhibitor. Antimicrob Agents Chemother 2011;55:813-21
  • Hare S, Smith SJ, Métifiot M, et al. Structural and functional analyses of the second-generation integrase strand transfer inhibitor dolutegravir (S/GSK1349572). Mol Pharmacol 2011;80:565-72
  • Hightower KE, Wang R, DeAnda F, et al. Dolutegravir (S/GSK1349572) exhibits significantly slower dissociation than raltegravir and elvitegravir from wild-type and integrase inhibitor-resistant HIV-1 integrase-DNA complexes. Antimicrob Agents Chemother 2011;55:4552-9
  • DeAnda F, Hightower KE, Nolte RT, et al. Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. PLoS One 2013;16:e77448
  • Min S, Song I, Borland J, et al. Pharmacokinetics and safety of S/GSK1349572, a next generation HIV integrase inhibitor, in healthy volunteers. Antimicrob Agents Chemother 2010;54:254-8
  • Min S, Sloan L, DeJesus E, et al. Antiviral activity, safety, and pharmacokinetics/pharmacodynamics of dolutegravir as 10-day monotherapy in HIV-1-infected adults. AIDS 2011;25:1737-45
  • Iwamoto M, Wenning LA, Petry AS, et al. Safety, tolerability, and Pharmacokinetics of Raltegravir after single and multiple doses in healthy subjects. Clin. Pharmacol. and Therapeutics 2008;83:293-9
  • DeJesus E, Berger D, Markowitz M, et al. Antiviral activity, Pharmacokinetics, and dose response of the HIV-1 integrase inhibitor GS-9137 (JTK-303) in treatment-naive and treatment-experienced patients. J Acquir Immune Defic Syndr 2006;43:1-5
  • van Lunzen J, Maggiolo JR, Rakhmanova A, et al. Once daily dolutegravir (S/GSK1349572) in combination therapy in antiretroviral-naive adults with HIV: planned interim 48 week results from SPRING-1, a dose-ranging, randomised, phase 2b trial. Lancet Infect Dis 2012;12:111-18
  • Stellbrink HJ, Reynes J, Lazzarin A, et al. Dolutegravir in antiretroviral-naive adults with HIV-1: 96-week results from a randomized dose-ranging study. AIDS 2013;27:1771-8
  • Raffi F, Rachlis A, Stellbrink HJ, et al. Once-daily dolutegravir versus raltegravir in antiretroviral-naive adults with HIV-1 infection: 48 week results from the randomised, double-blind, non-inferiority SPRING-2 study. Lancet 2013;381:735-43
  • Raffi F, Jaeger H, Quiros-Roldan E, et al. Once-daily dolutegravir versus twice-daily raltegravir in antiretroviral-naive adults with HIV-1 infection (SPRING-2 study): 96 week results from a randomised, double-blind, non-inferiority trial. Lancet Infect Dis 2013;13:927-35
  • Miller MM, Liedtke MD, Lockhart SM, Rathbun RC. The role of dolutegravir in the management of HIV infection. Infection and Drug Resistance 2015;8:19-29
  • Cruciani M, Malena M. Combination dolutegravir-abacavir-lamivudine in the management of HIV/AIDS: clinical utility and patient considerations. Patient Prefere Adherence 2015;9:299-310
  • Malet I, Delelis O, Valantin MA, et al. Mutations associated with failure of raltegravir treatment affect integrase sensitivity to the inhibitor in vitro. Antimicrob Agents Chemother 2008;52:1351-8
  • Billamboz M, Suchaud V, Bailly F, et al. 4-Substituted 2-hydroxyisoquinoline-1,3(2H,4H)-diones as a novel class of HIV-1 integrase inhibitors. ACS Med Chem Lett 2013;4:606-11
  • Suchaud V, Bailly F, Lion C, et al. Investigation of a novel series of 2-hydroxyisoquinoline-1,3(2H,4H)-diones as human immunodeficiency virus type 1 integrase inhibitors. J Med Chem 2014;57:4640-60
  • Quashie PK, Mesplede T, Han YS, et al. Characterization of the R263K mutation in HIV-1 integrase that confers low-level resistance to the second-generation integrase strand transfer inhibitor dolutegravir. J Virol 2012;86:2696-705
  • Anstett K, Mesplede T, Oliveira M, et al. Dolutegravir resistance mutation R263K cannot coexist in combination with many classical integrase inhibitor resistance substitutions. J Virol 2015;89:4681-4
  • Lataillade M, Chiarella J, Kozal MJ. Natural polymorphism of the HIV-1 integrase gene and mutations associated with integrase inhibitor resistance. Antivir Ther 2007;12:563-70
  • Rhee SY, Liu TF, Kiuchi M, et al. Natural variation of HIV-1 group M integrase: implications for a new class of antiretroviral inhibitors. Retrovirology 2008;5:74
  • Hachiya A, Ode H, Matsuda M, et al. Natural polymorphism S119R of HIV-1 integrase enhances primary INSTI resistance. Antivir Res 2015;119:84-8
  • Nichols G, Mills A, Grossberg R, et al. Antiviral activity of dolutegravir in subjects with failure on an integrase inhibitor-based regimen: week 24 phase 3 results from VIKING-3. J Int AIDS Soc 2012;15:18112
  • Engelman A, Kessl JJ, Kvaratskhelia M. Allosteric inhibition of HIV-1 integrase activity. Curr Opin Chem Biol 2013;17:339-45
  • Demeulemeester J, Chaltin P, Marchand A, et al. LEDGINs, non-catalytic site inhibitors of HIV-1 integrase: a patent review (2006 - 2014). Expert Opin Ther Pat 2014;24:609-32
  • Esposito F, Tramontano E. Past and future. Current drugs targeting HIV-1 integrase and reverse transcriptase-associated ribonuclease H activity: single and dual active site inhibitors. Antivir Chem Chemother 2014;23:129-44

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