LEDGINs, non-catalytic site inhibitors of HIV-1 integrase: a patent review (2006 – 2014)

Bibliography

• UNAIDS report on the global AIDS epidemic 2012 [Internet]. UNAIDS JUNPOHA. 2012. Available from: http://www.unaids.org/en/media/unaids/contentassets/documents/epidemiology/2012/gr2012/20121120_UNAIDS_Global_Report_2012_en.pdf [Last accessed 21 Aug 2013]
   Google Scholar
• Engelman A, Cherepanov P. The structural biology of HIV-1: mechanistic and therapeutic insights. Nat Rev Microbiol 2012;10(4):279-90
   PubMed Web of Science ®Google Scholar
• Cherepanov P, Maertens GN, Hare S. Structural insights into the retroviral DNA integration apparatus. Curr Opin Struct Biol 2011;21(2):249-56
   PubMed Web of Science ®Google Scholar
• U.S. Food and Drug Administration. 2013. Available from: http://www.fda.gov [Last accessed 21 Aug 2013]
   Google Scholar
• Christ F, Voet A, Marchand A, et al. Rational design of small-molecule inhibitors of the LEDGF/p75-integrase interaction and HIV replication. Nat Chem Biol 2010;6(6):442-8
   PubMed Web of Science ®Google Scholar
• Fenwick C, Bethell R, Bonneau P, et al. Identification of BI-C, a novel HIV-1 non-catalytic site integrase inhibitor. 18th Conference on Retroviruses and Opportunistic Infections; 27 February – 2 March 2011; Boston, MA, USA
   Google Scholar
• Jaskolski M, Alexandratos JN, Bujacz G, Wlodawer A. Piecing together the structure of retroviral integrase, an important target in AIDS therapy. FEBS J 2009;276(11):2926-46
   PubMedGoogle Scholar
• Li X, Krishnan L, Cherepanov P, Engelman A. Structural biology of retroviral DNA integration. Virology 2011;411(2):194-205
   PubMed Web of Science ®Google Scholar
• Nowotny M. Retroviral integrase superfamily: the structural perspective. EMBO Rep 2009;10(2):144-51
   PubMed Web of Science ®Google Scholar
• Hare S, Gupta SS, Valkov E, et al. Retroviral intasome assembly and inhibition of DNA strand transfer. Nature 2010;464(7286):232-6
   PubMed Web of Science ®Google Scholar
• FDA Isentress (raltegravir) new drug application (NDA) approval letter. Food and Drug Administration Rockville, MD 20857. 2007. Available from: http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2007/022145s000tr.pdf [Last accessed 17 Dec 2013]
   Google Scholar
• FDA Stribild (elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate) new drug application (NDA) approval letter [Internet]. Food and Drug Administration Silver Spring MD 20993. Available from: http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2012/0203100Orig1s000ltr.pdf [ cited 2013 Dec 17]
   Google Scholar
• FDA Tivicay (dolutegravir) new drug application (NDA) approval letter [Internet]. Food and Drug Administration Silver Spring MD 20993. 2013; Available from: http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2013/204790Orig1s000ltr.pdf [ Last accessed 17 Dec 2013]
   Google Scholar
• 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(5453):646-50
   PubMed Web of Science ®Google Scholar
• Demeulemeester J, De Maeyer M, Debyser Z. HIV-1 integrase drug discovery comes of age. Topics in medicinal chemistry. Springer, Berlin Heidelberg; 2014. p. 1-52
   Google Scholar
• Johnson VA, Calvez V, Günthard HF, et al. Update of the drug resistance mutations in HIV-1: march 2013. Top Antivir Med 2013;21(1):6-14
   PubMedGoogle Scholar
• Wainberg MA, Mesplède T, Quashie PK. The development of novel HIV integrase inhibitors and the problem of drug resistance. Curr Opin Virol 2012;2(5):656-62
   PubMedGoogle Scholar
• Al-Mawsawi LQ, Neamati N. Allosteric inhibitor development targeting HIV-1 integrase. ChemMedChem 2011;6(2):228-41
   PubMed Web of Science ®Google Scholar
• Voet AR, Maeyer MD, Debyser Z, Christ F. In search of second-generation HIV integrase inhibitors: targeting integration beyond strand transfer. Future Med Chem 2009;1(7):1259-74
   PubMedGoogle Scholar
• Demeulemeester J, Christ F, De Maeyer M, Debyser Z. Fueling HIV-1 integrase drug design with structural insights. Drug Discov Today Technol 2012;9(3):e175-226
   Google Scholar
• Engelman A, Kessl JJ, Kvaratskhelia M. Allosteric inhibition of HIV-1 integrase activity. Curr Opin Chem Biol 2013;17(3):339-45
   PubMed Web of Science ®Google Scholar
• Christ F, Debyser Z. The LEDGF/p75 integrase interaction, a novel target for anti-HIV therapy. Virology 2013;435(1):102-9
   PubMed Web of Science ®Google Scholar
• Kessl JJ, Jena N, Koh Y, et al. Multimode, cooperative mechanism of action of allosteric HIV-1 integrase inhibitors. J Biol Chem 2012;287(20):16801-11
   PubMed Web of Science ®Google Scholar
• Ge H, Si Y, Roeder RG. Isolation of cDNAs encoding novel transcription coactivators p52 and p75 reveals an alternate regulatory mechanism of transcriptional activation. EMBO J 1998;17(22):6723-9
   PubMedGoogle Scholar
• Eidahl JO, Crowe BL, North JA, et al. Structural basis for high-affinity binding of LEDGF PWWP to mononucleosomes. Nucleic Acids Res 2013;41(6):3924-36
   PubMed Web of Science ®Google Scholar
• van Nuland R, van Schaik FM, Simonis M, et al. Nucleosomal DNA binding drives the recognition of H3K36-methylated nucleosomes by the PSIP1-PWWP domain. Epigenetics Chromatin 2013;6(1):12
   PubMedGoogle Scholar
• Llano M, Vanegas M, Hutchins N, et al. Identification and characterization of the chromatin-binding domains of the HIV-1 integrase interactor LEDGF/p75. J Mol Biol 2006;360(4):760-73
   PubMed Web of Science ®Google Scholar
• Maertens G, Cherepanov P, Debyser Z, et al. Identification and characterization of a functional nuclear localization signal in the HIV-1 integrase interactor LEDGF/p75. J Biol Chem 2004;279(32):33421-9
   PubMedGoogle Scholar
• Tsutsui KM, Sano K, Hosoya O, et al. Nuclear protein LEDGF/p75 recognizes supercoiled DNA by a novel DNA-binding domain. Nucleic Acids Res 2011;39(12):5067-81
   PubMedGoogle Scholar
• De Rijck J, Bartholomeeusen K, Ceulemans H, et al. High-resolution profiling of the LEDGF/p75 chromatin interaction in the ENCODE region. Nucleic Acids Res 2010;38(18):6135-47
   PubMed Web of Science ®Google Scholar
• Cherepanov P, Sun Z-YJ, Rahman S, et al. Solution structure of the HIV-1 integrase-binding domain in LEDGF/p75. Nat Struct Mol Biol 2005;12(6):526-32
   PubMed Web of Science ®Google Scholar
• Cherepanov P, Devroe E, Silver PA, Engelman A. Identification of an evolutionarily conserved domain in human lens epithelium-derived growth factor/transcriptional co-activator p75 (LEDGF/p75) that binds HIV-1 integrase. J Biol Chem 2004;279(47):48883-92
   PubMed Web of Science ®Google Scholar
• Schrijvers R, De Rijck J, Demeulemeester J, et al. LEDGF/p75-independent HIV-1 replication demonstrates a role for HRP-2 and remains sensitive to inhibition by LEDGINs. PLoS Pathog 2012;8(3):e1002558
   PubMed Web of Science ®Google Scholar
• Wang H, Jurado KA, Wu X, et al. HRP2 determines the efficiency and specificity of HIV-1 integration in LEDGF/p75 knockout cells but does not contribute to the antiviral activity of a potent LEDGF/p75-binding site integrase inhibitor. Nucleic Acids Res 2012;40(22):11518-30
   PubMedGoogle Scholar
• Ciuffi A, Llano M, Poeschla E, et al. A role for LEDGF/p75 in targeting HIV DNA integration. Nat Med 2005;11(12):1287-9
   PubMed Web of Science ®Google Scholar
• Shun M-C, Raghavendra NK, Vandegraaff N, et al. LEDGF/p75 functions downstream from preintegration complex formation to effect gene-specific HIV-1 integration. Genes Dev 2007;21(14):1767-78
   PubMed Web of Science ®Google Scholar
• Cherepanov P, Maertens G, Proost P, et al. HIV-1 integrase forms stable tetramers and associates with LEDGF/p75 protein in human cells. J Biol Chem 2003;278(1):372-81
   PubMed Web of Science ®Google Scholar
• Raghavendra NK, Engelman A. LEDGF/p75 interferes with the formation of synaptic nucleoprotein complexes that catalyze full-site HIV-1 DNA integration in vitro: implications for the mechanism of viral cDNA integration. Virology 2007;360(1):1-5
   PubMedGoogle Scholar
• Llano M, Delgado S, Vanegas M, Poeschla EM. Lens epithelium-derived growth factor/p75 prevents proteasomal degradation of HIV-1 integrase. J Biol Chem 2004;279(53):55570-7
   PubMed Web of Science ®Google Scholar
• Maertens G, Cherepanov P, Pluymers W, et al. LEDGF/p75 is essential for nuclear and chromosomal targeting of HIV-1 integrase in human cells. J Biol Chem 2003;278(35):33528-39
   PubMed Web of Science ®Google Scholar
• De Rijck J, Vandekerckhove L, Gijsbers R, et al. Overexpression of the lens epithelium-derived growth factor/p75 integrase binding domain inhibits human immunodeficiency virus replication. J Virol 2006;80(23):11498-509
   PubMed Web of Science ®Google Scholar
• Debyser Z, Cherepanov P, De Clercq E. Integrase cofactor. WO04029246; 2004
   Google Scholar
• Legrain P, Rain J-C, Benarous R, et al. Protein-protein interactions in human immunodeficiency virus. WO03046176; 2003
   Google Scholar
• Debyser Z, Cherepanov P, De Clercq E. Integrase cofactor. US7514233; 2009
   Google Scholar
• Debyser Z, Cherepanov P, De Clercq E. Integrase cofactor. EP1546331; 2012
   Google Scholar
• Cherepanov P, Ambrosio ALB, Rahman S, et al. Structural basis for the recognition between HIV-1 integrase and transcriptional coactivator p75. Proc Natl Acad Sci USA 2005;102(48):17308-13
   PubMed Web of Science ®Google Scholar
• Hayouka Z, Rosenbluh J, Levin A, et al. Inhibiting HIV-1 integrase by shifting its oligomerization equilibrium. Proc Natl Acad Sci USA 2007;104(20):8316-21
   PubMed Web of Science ®Google Scholar
• Hou Y, McGuinness DE, Prongay AJ, et al. Screening for antiviral inhibitors of the HIV integrase-LEDGF/p75 interaction using the AlphaScreen luminescent proximity assay. J Biomol Screen 2008;13(5):406-14
   PubMedGoogle Scholar
• Du L, Zhao Y, Chen J, et al. D77, one benzoic acid derivative, functions as a novel anti-HIV-1 inhibitor targeting the interaction between integrase and cellular LEDGF/p75. Biochem Biophys Res Commun 2008;375(1):139-44
   PubMed Web of Science ®Google Scholar
• De Luca L, Barreca ML, Ferro S, et al. Pharmacophore-based discovery of small-molecule inhibitors of protein-protein interactions between HIV-1 integrase and cellular cofactor LEDGF/p75. ChemMedChem 2009;4(8):1311-16
   PubMed Web of Science ®Google Scholar
• Fan X, Zhang F-H, Al-Safi RI, et al. Design of HIV-1 integrase inhibitors targeting the catalytic domain as well as its interaction with LEDGF/p75: a scaffold hopping approach using salicylate and catechol groups. Bioorg Med Chem 2011;19(16):4935-52
   PubMed Web of Science ®Google Scholar
• De Luca L, Ferro S, Gitto R, et al. Small molecules targeting the interaction between HIV-1 integrase and LEDGF/p75 cofactor. Bioorg Med Chem 2010;18(21):7515-21
   PubMed Web of Science ®Google Scholar
• Peat TS, Rhodes DI, Vandegraaff N, et al. Small molecule inhibitors of the LEDGF site of human immunodeficiency virus integrase identified by fragment screening and structure based design. PLoS One 2012;7(7):e40147
   Web of Science ®Google Scholar
• Christ F, Shaw S, Demeulemeester J, et al. Small-molecule inhibitors of the LEDGF/p75 binding site of integrase block HIV replication and modulate integrase multimerization. Antimicrob Agents Chemother 2012;56(8):4365-74
   PubMed Web of Science ®Google Scholar
• Fenwick CW, Tremblay S, Wardrop E, et al. Resistance studies with HIV-1 non-catalytic site integrase inhibitors. 16 ed. International Workshop on HIV & Hepatitis Virus Drug Resistance and Curative Strategies; 7 – 11 June 2011; Los Cabos, Mexico
   Google Scholar
• Aslanyan S, Ballow C, Sabo J. Safety and pharmacokinetics (PK) of single rising oral doses of a novel HIV integrase inhibitor in healthy volunteers. 51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); 17 – 20 September 2011; Chicago, IL, USA
   Google Scholar
• Boehringer Ingelheim and Gilead sign license agreement for novel HIV non-catalytic integrase inhibitors. 2011.Boehringer Ingelheim. Available from: http://www.boehringer-ingelheim.com/news/news_releases/press_releases/2011/06_october_2011_gilead.html [Last accessed 2013 Aug 27]
   Google Scholar
• Tsiang M, Jones GS, Niedziela-Majka A, et al. New class of HIV-1 integrase (IN) inhibitors with a dual mode of action. J Biol Chem 2012;287(25):21189-203
   PubMed Web of Science ®Google Scholar
• Tsantrizos YS, Boes M, Brochu C, et al. Inhibitors of human immunodeficiency virus replication. WO07131350; 2007
   Google Scholar
• Tsantrizos YS, Bailey MD, Bilodeau F, et al. Inhibitors of human immunodeficiency virus replication. WO09062285; 2009
   Google Scholar
• Michel P, Ley SV. Synthesis of enantiomers of butane-1,2-diacetal-protected glyceraldehyde and of (R, R)-butane-1,2-diacetal-protected glycolic acid. Synthesis 2003;35(10):1598-602
   Google Scholar
• Sharpless KB, Amberg W, Bennani YL, et al. The osmium-catalyzed asymmetric dihydroxylation: a new ligand class and a process improvement. J Org Chem 1992;57(10):2768-71
   Google Scholar
• Carson R, Fader L, Kawai S, et al. Inhibitors of human immunodeficiency virus replication. WO09062288; 2009
   Google Scholar
• Tsantrizos YS, Bailey MD, Bilodeau F, et al. Inhibitors of human immunodeficiency virus replication. WO09062289; 2009
   Google Scholar
• Tsantrizos YS, Bailey MD, Bhardwaj N, et al. Inhibitors of human immunodeficiency virus replication. WO09062308; 2009
   Google Scholar
• Yoakim C, Bailey MD, Bilodeau F, et al. Inhibitors of human immunodeficiency virus replication. WO10130034; 2010
   Google Scholar
• Bardiot D, Chaltin P, Christ F, et al. Thieno [2, 3-B] pyridine derivatives as viral replication inhibitors. WO10130842; 2010
   Google Scholar
• Pauwels R, Balzarini J, Baba M, et al. Rapid and automated tetrazolium-based colorimetric assay for the detection of anti-HIV compounds. J Virol Methods 1988;20(4):309-21
   PubMed Web of Science ®Google Scholar
• Chaltin P, Debyser Z, De Maeyer M, et al. Novel viral replication Inhibitors. WO11015641; 2011
   Google Scholar
• Carlens G, Chaltin P, Christ F, et al. Novel antiviral compounds. WO11076765; 2011
   Google Scholar
• Chaltin P, Christ F, Debyser Z, et al. Novel antiviral compounds. WO12065963; 2012
   Google Scholar
• KU Leuven enters into license agreement with Pfizer. KU Leuven R&D. 2010. Available from: https://lrd.kuleuven.be/en/news/kuleuven-enters-into-license-agreement-with-pfizer [Last accessed 27 Aug 2013]
   Google Scholar
• Bell AS, Gardner IB, Pryde DC, et al. Inhibitors of HIV replication. WO12066442; 2012
   Google Scholar
• Llano M, Saenz DT, Meehan A, et al. An essential role for LEDGF/p75 in HIV integration. Science 2006;314(5798):461-4
   PubMed Web of Science ®Google Scholar
• Babaoglu K, Bjornson K, Guo H, et al. 2 -quinolinyl- acetic acid derivatives as HIV antiviral compounds. WO12003498; 2012
   Google Scholar
• Babaoglu K, Bjornson K, Guo H, et al. Napht- 2 -ylacetic acid derivatives to treat aids. WO12003497; 2012
   Google Scholar
• Li W, De Croos P, Fandrick KR, et al. Process for the preparation of an HIV integrase inhibitor. WO12138670; 2012
   Google Scholar
• Chen Y-C, Wu T-F, Deng J-G, et al. Multiple dendritic catalysts for asymmetric transfer hydrogenation. J Org Chem 2002;67(15):5301-6
   PubMedGoogle Scholar
• Tang W, Capacci AG, Wei X, et al. A general and special catalyst for Suzuki-Miyaura coupling processes. Angew Chem Int Ed Engl 2010;49(34):5879-83
   PubMed Web of Science ®Google Scholar
• Tang W, Keshipeddy S, Zhang Y, et al. Efficient monophosphorus ligands for palladium-catalyzed Miyaura borylation. Org Lett 2011;13(6):1366-9
   PubMedGoogle Scholar
• Li ZJ, Li Z, Luo L, et al. Solid state forms of HIV inhibitor. WO12138669; 2012
   Google Scholar
• Mitchell ML, Roethle PA, Xu L, et al. Benzothiazole compounds and their pharmaceutical use. WO12145728; 2012
   Google Scholar
• Babaoglu K, Bjornson KL, Hrvatin P, et al. 2- (tert - butoxy) -2- (7 -methylquinolin- 6 - yl) acetic acid derivatives for treating aids. WO13103724; 2013
   Google Scholar
• Babaoglu K, Brizgys G, Guo H, et al. Napthalene acetic acid derivatives against HIV infection. WO13103738; 2013
   Google Scholar
• Babaoglu K, Brizgys G, Cha J, et al. Benzothiazol- 6 -yl acetic acid derivatives and their use for treating an HIV infection. WO13159064; 2013
   Google Scholar
• Pendri A, Li G, Gerritz S, et al. Inhibitors of human immunodeficiency virus replication. WO12033735; 2012
   Google Scholar
• Naidu BN, Patel M. Inhibitors of human immunodeficiency virus replication. WO13025584; 2013
   Google Scholar
• Zheng ZB, D'Andrea S, Langley DR, Naidu BN. Inhibitors of human immunodeficiency virus replication. WO13134142; 2013
   Google Scholar
• Pendri A, Langley DR, Gerritz S, et al. Fused pyrimidines as inhibitors of immunodeficiency virus replication. WO13134113; 2013
   Google Scholar
• Walker MA, Sorenson ME, Naidu BN, et al. Inhibitors of human immunodeficiency virus replication. WO13123148; 2013
   Google Scholar
• De La Rosa MA, Haydar SN, Johns BA, Velthuisen EJ. Isoquinoline compounds and methods for treating HIV. WO12102985; 2012
   Google Scholar
• De La Rosa MA, Johns BA, Samano V, et al. Azaindole compounds and methods for treating HIV. WO13012649; 2013
   Google Scholar
• Haydar SN, Johns BA, Velthuisen EJ. Pyrrolopyridinone compounds and methods for treating HIV. WO13043553; 2013
   Google Scholar
• De La Rosa MA, Johns BA, Kazmierski WM, et al. Compounds and methods for treating HIV. WO14009794; 2014
   Google Scholar
• Hattori K, Kurihara N, Iwaki T, et al. HIV replication inhibitor. WO13002357; 2013
   Google Scholar
• Iwaki T, Tomita K. HIV replication inhibitor. WO13062028; 2013
   Google Scholar
• Sugiyama S, Akiyama T, Taoda Y. HIV replication inhibitor. WO1315762; 2013
   Google Scholar
• Chasset S, Chevreuil F, Ledoussal B, et al. Inhibitors of viral replication, their process of preparation and their therapeutical uses. WO12137181; 2012
   Google Scholar
• Chasset S, Chevreuil F, Ledoussal B, et al. Inhibitors of viral replication, their process of preparation and their therapeutical uses. WO12140243; 2012
   Google Scholar
• Son JC, Kim BJ, Kim JH, et al. Novel antiviral pyrrolopyridine derivative and a production method for same. WO13073875; 2013
   Google Scholar
• Rhodes DI, Peat TS, Vandegraaff N, et al. Crystal structures of novel allosteric peptide inhibitors of HIV integrase identify new interactions at the LEDGF binding site. ChemBioChem 2011;12(15):2311-15
   PubMed Web of Science ®Google Scholar
• Serrao E, Debnath B, Otake H, et al. Fragment-based discovery of 8-hydroxyquinoline inhibitors of the HIV-1 integrase–lens epithelium-derived growth factor/p75 (IN–LEDGF/p75) interaction. J Med Chem 2013;56(6):2311-22
   PubMed Web of Science ®Google Scholar
• Hu G, Li X, Zhang X, et al. Discovery of inhibitors to block interactions of HIV-1 integrase with human LEDGF/p75 via structure-based virtual screening and bioassays. J Med Chem 2012;55(22):10108-17
   PubMedGoogle Scholar
• Sanchez TW, Debnath B, Christ F, et al. Discovery of novel inhibitors of LEDGF/p75-IN protein-protein interactions. Bioorg Med Chem 2013;21(4):957-63
   PubMedGoogle Scholar
• Rhodes DI, Peat TS, Vandegraaff N, et al. Structural basis for a new mechanism of inhibition of HIV-1 integrase identified by fragment screening and structure-based design. Antivir Chem Chemother 2011;21(4):155-68
   PubMedGoogle Scholar
• Jurado KA, Wang H, Slaughter A, et al. Allosteric integrase inhibitor potency is determined through the inhibition of HIV-1 particle maturation. Proc Natl Acad Sci USA 2013;110(21):8690-5
   PubMed Web of Science ®Google Scholar
• Feng L, Sharma A, Slaughter A, et al. The A128T resistance mutation reveals aberrant protein multimerization as the primary mechanism of action of allosteric HIV-1 integrase inhibitors. J Biol Chem 2013;288(22):15813-20
   PubMed Web of Science ®Google Scholar
• Kessl JJ, Li M, Ignatov M, et al. FRET analysis reveals distinct conformations of IN tetramers in the presence of viral DNA or LEDGF/p75. Nucleic Acids Res 2011;39(20):9009-22
   PubMedGoogle Scholar
• McKee CJ, Kessl JJ, Shkriabai N, et al. Dynamic modulation of HIV-1 integrase structure and function by cellular lens epithelium-derived growth factor (LEDGF) protein. J Biol Chem 2008;283(46):31802-12
   PubMedGoogle Scholar
• Schrijvers R, Demeulemeester J, De Rijck J, et al. Characterization of rare lens epithelium-derived growth factor/p75 genetic variants identified in HIV-1 long-term nonprogressors. AIDS 2013;27(4):539-43
   PubMedGoogle Scholar
• Le Rouzic E, Bonnard D, Chasset S, et al. Dual inhibition of HIV-1 replication by integrase-LEDGF allosteric inhibitors is predominant at the post-integration stage. Retrovirology 2013;10(1):144
   PubMedGoogle Scholar
• Demeulemeester J, Tintori C, Botta M, et al. Development of an AlphaScreen-based HIV-1 integrase dimerization assay for discovery of novel allosteric inhibitors. J Biomol Screen 2012;17(5):618-28
   PubMedGoogle Scholar
• Tsiang M, Jones GS, Hung M, et al. Dithiothreitol causes HIV-1 integrase dimer dissociation while agents interacting with the integrase dimer interface promote dimer formation. Biochemistry 2011;50(10):1567-81
   PubMedGoogle Scholar
• Engelman A, Englund G, Orenstein JM, et al. Multiple effects of mutations in human immunodeficiency virus type 1 integrase on viral replication. J Virol 1995;69(5):2729-36
   PubMed Web of Science ®Google Scholar
• Desimmie BA, Schrijvers R, Demeulemeester J, et al. LEDGINs inhibit late stage HIV-1 replication by modulating integrase multimerization in the virions. Retrovirology 2013;10:57
   PubMed Web of Science ®Google Scholar
• Balakrishnan M, Yant SR, Tsai L, et al. Non-catalytic site HIV-1 integrase inhibitors disrupt core maturation and induce a reverse transcription block in target cells. PLoS One 2013;8(9):e74163
   PubMed Web of Science ®Google Scholar
• Jurado KA, Engelman A. Multimodal mechanism of action of allosteric HIV-1 integrase inhibitors. Expert Rev Mol Med 2013;15:e14
   Google Scholar
• Shen L, Rabi SA, Sedaghat AR, et al. A critical subset model provides a conceptual basis for the high antiviral activity of major HIV drugs. Sci Transl Med 2011;3(91):91ra63
   PubMedGoogle Scholar
• Fenwick C, Bethell R, Cordingley M. BI 224436, a non-catalytic site integrase inhibitor, is a potent inhibitor of the replication of treatment-naive and raltegravir-resistant clinical isolates of HIV-1. 51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); 17 – 20 September 2011; Chicago, IL, USA
   Google Scholar
• Messiaen P, Wensing AMJ, Fun A, et al. Clinical use of HIV integrase inhibitors: a systematic review and meta-analysis. PLoS One 2013;8(1):e52562
   PubMed Web of Science ®Google Scholar
• 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(5):740-8
   PubMed Web of Science ®Google Scholar
• 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(Suppl 4):18112
   Google Scholar
• Yoakim C, Amad M, Bailey M. Preclinical profile of BI 224436, a novel HIV-1 non-catalytic site integrase inhibitor. 51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); 17 – 20 September 2011; Chicago, IL, USA
   Google Scholar
• Brown A, McSharry J, Kulawy R. Pharmacodynamics of BI 224436 for HIV-1 in an in vitro hollow fiber infection model system. 51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); 17 – 20 September 2011; Chicago, IL, USA
   Google Scholar
• Fader LD, Malenfant E, Parisien M, et al. Discovery of BI 224436, a non-catalytic site integrase inhibitor (NCINI) of HIV-1. ACS Med Chem Lett 2014
   Google Scholar