integrase inhibitors


Summary: Compounds which inhibit or antagonize biosynthesis or actions of integrase.

Top Publications

  1. Hazuda D, Young S, Guare J, Anthony N, Gomez R, Wai J, et al. Integrase inhibitors and cellular immunity suppress retroviral replication in rhesus macaques. Science. 2004;305:528-32 pubmed
    ..These studies demonstrate integrase inhibitor activity in vivo and suggest that cellular immunity facilitates chemotherapeutic efficacy in retroviral infections. ..
  2. Damond F, Lariven S, Roquebert B, Males S, Peytavin G, Morau G, et al. Virological and immunological response to HAART regimen containing integrase inhibitors in HIV-2-infected patients. AIDS. 2008;22:665-6 pubmed publisher
  3. Goethals O, Clayton R, Van Ginderen M, Vereycken I, Wagemans E, Geluykens P, et al. Resistance mutations in human immunodeficiency virus type 1 integrase selected with elvitegravir confer reduced susceptibility to a wide range of integrase inhibitors. J Virol. 2008;82:10366-74 pubmed publisher
    ..The first generation of integrase inhibitors recently approved or currently in late-stage clinical trials shows great promise for the treatment of human ..
  4. Savarino A, Pistello M, D Ostilio D, Zabogli E, Taglia F, Mancini F, et al. Human immunodeficiency virus integrase inhibitors efficiently suppress feline immunodeficiency virus replication in vitro and provide a rationale to redesign antiretroviral treatment for feline AIDS. Retrovirology. 2007;4:79 pubmed
    ..Integrase strand transfer inhibitors (INSTIs) are emerging as a promising new drug class for HIV-1 treatment, and we evaluated the possibility of inhibiting FIV replication using INSTIs...
  5. Phuphuakrat A, Pasomsub E, Kiertiburanakul S, Chantratita W, Sungkanuparph S. HIV type 1 integrase polymorphisms in treatment-naive and treatment-experienced HIV type 1-infected patients in Thailand where HIV type 1 subtype A/E predominates. AIDS Res Hum Retroviruses. 2012;28:937-43 pubmed publisher
    ..INI-RAMs are rare in both treatment-naive and treatment-experienced patients in Thailand. This suggested that INI should be active in patients who are naive to INI in Thailand. ..
  6. Waki K, Sugawara Y. Implications of integrase inhibitors for HIV-infected transplantation recipients: raltegravir and dolutegravir (S/GSK 1349572). Biosci Trends. 2011;5:189-91 pubmed
    ..Of interest, integrase inhibitors (INIs) - novel, potent anti-HIV drugs - are mainly metabolized by uridine diphosphate ..
  7. van Hal S, Herring B, Deris Z, Wang B, Saksena N, Dwyer D. HIV-1 integrase polymorphisms are associated with prior antiretroviral drug exposure. Retrovirology. 2009;6:12 pubmed publisher
    ..Based on these findings, we would recommend ongoing surveillance of integrase mutations, and integrase region sequencing for patients prior to commencement of integrase inhibitors.
  8. Kawasuji T, Johns B, Yoshida H, Taishi T, Taoda Y, Murai 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 pubmed publisher
    Our group has focused on expanding the scope of a two-metal binding pharmacophore concept to explore HIV-1 integrase inhibitors through medicinal chemistry efforts to design novel scaffolds which allow for improvement of pharmacokinetic (..
  9. Roquebert B, Damond F, Collin G, Matheron S, Peytavin G, Benard A, et al. HIV-2 integrase gene polymorphism and phenotypic susceptibility of HIV-2 clinical isolates to the integrase inhibitors raltegravir and elvitegravir in vitro. J Antimicrob Chemother. 2008;62:914-20 pubmed publisher
    ..This new class of antiretroviral drugs thus represents a novel therapeutic possibility for HIV-2-infected patients who otherwise have few treatment options. ..

More Information


  1. Kessl J, Jena N, Koh Y, Taskent Sezgin H, Slaughter A, Feng L, et al. Multimode, cooperative mechanism of action of allosteric HIV-1 integrase inhibitors. J Biol Chem. 2012;287:16801-11 pubmed publisher
  2. Parczewski M, Bander D, Urbańska A, Boron Kaczmarska A. HIV-1 integrase resistance among antiretroviral treatment naive and experienced patients from Northwestern Poland. BMC Infect Dis. 2012;12:368 pubmed publisher
    ..In the treatment failing patients selection of drug resistance occurred rapidly and followed the typical drug resistance pathways. Preexisting integrase polymorphisms were not associated with the treatment failure. ..
  3. Anstett K, Brenner B, Mesplede T, Wainberg M. HIV drug resistance against strand transfer integrase inhibitors. Retrovirology. 2017;14:36 pubmed publisher
    ..This highlights the unpredictability of HIV resistance to these inhibitors, which is of concern as CAB and BIC proceed in their clinical development. ..
  4. Li H, Yuan G, Du D. Investigation of formation, recognition, stabilization, and conversion of dimeric G-quadruplexes of HIV-1 integrase inhibitors by electrospray ionization mass spectrometry. J Am Soc Mass Spectrom. 2008;19:550-9 pubmed publisher
    ..structures of d(GGGTGGGTGGGTGGGT) (S1) and d(GTGGTGGGTGGGTGGGT) (S2), the potent nanomolar HIV-1 integrase inhibitors, were detected by electrospray ionization mass spectrometry (ESI-MS) for the first time...
  5. Nair V, Okello M. Integrase Inhibitor Prodrugs: Approaches to Enhancing the Anti-HIV Activity of β-Diketo Acids. Molecules. 2015;20:12623-51 pubmed publisher
    ..This review article focuses largely on the design of integrase inhibitors that are β-diketo acids constructed on pyridinone scaffolds...
  6. Bao K, Wang H, Miller J, Erie D, Skalka A, Wong I. Functional oligomeric state of avian sarcoma virus integrase. J Biol Chem. 2003;278:1323-7 pubmed
    ..These results suggest that tetramer formation may be a requisite step during catalysis with ramifications for antiviral design strategies targeting the structurally homologous human immunodeficiency virus, type 1 (HIV-1) integrase. ..
  7. Xue P, Lu H, Zhu Y, Ju X, Pannecouque C, Zheng X, et al. Design and synthesis of hybrids of diarylpyrimidines and diketo acids as HIV-1 inhibitors. Bioorg Med Chem Lett. 2017;27:1640-1643 pubmed publisher
    Based on the strategy of molecular hybridization, diketo acid fragment as a classical phamacophore of integrase inhibitors was introduced to reverse transcriptase inhibitors diarylpyrimidines to design a series of diarylpyrimidine-diketo ..
  8. Serrano Villar S, Zhou Y, Rodgers A, Moreno S. Different impact of raltegravir versus efavirenz on CD4/CD8 ratio recovery in HIV-infected patients. J Antimicrob Chemother. 2017;72:235-239 pubmed
    ..Raltegravir showed faster CD4/CD8 ratio normalization compared with efavirenz, a finding with potential clinical implications. Whether other integrase inhibitors have a similar impact for this outcome remains to be explored.
  9. Pluymers W, Neamati N, Pannecouque C, Fikkert V, Marchand C, Burke T, et al. Viral entry as the primary target for the anti-HIV activity of chicoric acid and its tetra-acetyl esters. Mol Pharmacol. 2000;58:641-8 pubmed
    ..Although inhibition of HIV integrase activity by L-CA and its derivatives was confirmed in an oligonucleotide-driven assay, integrase carrying the G140S mutation was inhibited to the same extent as the wild-type integrase. ..
  10. Tsukada K, Oka S. [Advance and perspective of antiretroviral therapy]. Nihon Rinsho. 2010;68:389-94 pubmed
    ..Raltegravir, the first approved integrase inhibitor (INI), shows preferable safety profile. When long-term reliability of INI is proven, antiretroviral combination will be individualized by choosing the optimal drug from 4 classes. ..
  11. Luo Z, Tan J, Zeng Y, Wang C, Hu L. Development of integrase inhibitors of quinolone acid derivatives for treatment of AIDS: an overview. Mini Rev Med Chem. 2010;10:1046-57 pubmed
    ..This review focuses on small-molecules of quinolone acid derivatives, which have the similar pharmacophore of ?-diketoacids, as integrase inhibitors with antiviral activity.
  12. Scourfield A, Waters L, Nelson M. Drug combinations for HIV: what's new?. Expert Rev Anti Infect Ther. 2011;9:1001-11 pubmed publisher
    ..This article will focus on the evidence for current therapies and strategies in ART-naive individuals and the potential for use of novel agents in the future. ..
  13. Sakkhachornphop S, Thongkum W, Tayapiwatana C. Novel 3'-Processing Integrase Activity Assay by Real-Time PCR for Screening and Identification of HIV-1 Integrase Inhibitors. Biomed Res Int. 2015;2015:853891 pubmed publisher
    ..This real-time PCR assay has been shown to be effective and inexpensive for a high-throughput screening of novel IN inhibitors. ..
  14. Dalla Pria A, Bendle M, Ramaswami R, Boffito M, Bower M. The pharmacokinetics of high-dose methotrexate in people living with HIV on antiretroviral therapy. Cancer Chemother Pharmacol. 2016;77:653-7 pubmed publisher
    ..71), eGFR (p = 0.67) or use of non-nucleoside reverse transcriptase inhibitors (NNRTIs) or integrase inhibitors (p = 0.15). Similarly, different NRTI backbones did not affect MTX elimination kinetics (p = 0...
  15. Nishana M, Nilavar N, Kumari R, Pandey M, Raghavan S. HIV integrase inhibitor, Elvitegravir, impairs RAG functions and inhibits V(D)J recombination. Cell Death Dis. 2017;8:e2852 pubmed publisher
    b>Integrase inhibitors are a class of antiretroviral drugs used for the treatment of AIDS that target HIV integrase, an enzyme responsible for integration of viral cDNA into host genome...
  16. Dehority W, Abadi J, Wiznia A, Viani R. Use of Integrase Inhibitors in HIV-Infected Children and Adolescents. Drugs. 2015;75:1483-97 pubmed publisher
    ..Dolutegravir, a second-generation integrase inhibitor, is approved for those older than 12 years. This review summarizes the use of integrase inhibitors in children and adolescents, and highlights the results of recent clinical trials.
  17. Poveda E, Hernández Quero J, Pérez Elías M, Ribas M, Martínez Madrid O, Flores J, et al. Genotypic tropism testing of proviral DNA to guide maraviroc initiation in aviraemic subjects: 48-week analysis of results from the PROTEST study. HIV Med. 2017;18:482-489 pubmed publisher
    ..inhibitors (PIs) in 62% of subjects, nonnucleoside reverse transcriptase inhibitors (NNRTIs) in 36%, and integrase inhibitors (INIs) in 2%...
  18. Fan W, Wang Z, Li H, Fossey J, Deng W. A straightforward and efficient synthetic access to biologically active marine sesterterpenoids, sesterstatins 4 and 5. Chem Commun (Camb). 2011;47:2961-3 pubmed publisher
    ..A straightforward and efficient synthesis of sesterstatins 4 and 5 is reported, in which the reductive Heck cyclisation was employed as the key step for constructing the D ring. ..
  19. Queffélec C, Bailly F, Mbemba G, Mouscadet J, Hayes S, Debyser Z, et al. Synthesis and antiviral properties of some polyphenols related to Salvia genus. Bioorg Med Chem Lett. 2008;18:4736-40 pubmed publisher
    ..Both compounds together with the acid part of salvianolic acid D were active as HIV-1 integrase inhibitors at the submicromolar level. But they did not inhibit the replication of the virus on MT-4 cells.
  20. Alves C, Martí S, Castillo R, Andres J, Moliner V, Tuñón I, et al. A quantum mechanic/molecular mechanic study of the wild-type and N155S mutant HIV-1 integrase complexed with diketo acid. Biophys J. 2008;94:2443-51 pubmed
    ..These results might be useful to design compounds with more interesting anti-HIV-1 IN activity on the basis of its three-dimensional structure. ..
  21. Zazzi M, Cozzi Lepri A, Prosperi M. Computer-Aided Optimization of Combined Anti-Retroviral Therapy for HIV: New Drugs, New Drug Targets and Drug Resistance. Curr HIV Res. 2016;14:101-9 pubmed
    ..prediction algorithms for the nucleotide/nucleoside/non-nucleoside reverse transcriptase, protease and integrase inhibitors as well as coreceptor antagonists are currently available, routinely used, and have been validated ..
  22. Theys K, Abecasis A, Libin P, Gomes P, Cabanas J, Camacho R, et al. Discordant predictions of residual activity could impact dolutegravir prescription upon raltegravir failure. J Clin Virol. 2015;70:120-127 pubmed publisher
    Dolutegravir is approved for the treatment of HIV-1 patients exposed to other integrase inhibitors, but the decision to use dolutegravir in this setting should be informed by drug resistance testing...
  23. Heger E, Theis A, Remmel K, Walter H, Pironti A, Knops E, et al. Development of a phenotypic susceptibility assay for HIV-1 integrase inhibitors. J Virol Methods. 2016;238:29-37 pubmed publisher
    ..Since integrase inhibitors are essential components of recent antiretroviral combination therapies, phenotypic resistance data, in ..
  24. Esposito I, Labarga P, Barreiro P, Fernandez Montero J, de Mendoza C, Benítez Gutiérrez L, et al. Dual antiviral therapy for HIV and hepatitis C - drug interactions and side effects. Expert Opin Drug Saf. 2015;14:1421-34 pubmed publisher
    ..e., ledipasvir) and HIV integrase inhibitors (i.e...
  25. Montagna C, Mazzuti L, Falasca F, Maida P, Bucci M, D Ettorre G, et al. Trends in drug resistance-associated mutations in a real-life cohort of Italian patients infected with HIV-1. J Glob Antimicrob Resist. 2015;3:267-272 pubmed publisher
    ..Interestingly, analysis of the integrase gene disclosed an increased resistance to integrase inhibitors, mainly regarding N155H, detected in 32.6% of raltegravir-treated patients in 2012-2014...
  26. Katlama C, Soulie C, Caby F, Denis A, Blanc C, Schneider L, et al. Dolutegravir as monotherapy in HIV-1-infected individuals with suppressed HIV viraemia. J Antimicrob Chemother. 2016;71:2646-50 pubmed publisher
    ..Nine patients with a year of follow-up remained virally suppressed. Dolutegravir has the potency to be further investigated as a single ART in randomized studies, particularly in patients with no prior exposure to integrase inhibitors.
  27. Agharbaoui F, Hoyte A, Ferro S, Gitto R, Buemi M, Fuchs J, et al. Computational and synthetic approaches for developing Lavendustin B derivatives as allosteric inhibitors of HIV-1 integrase. Eur J Med Chem. 2016;123:673-683 pubmed publisher
    ..Taken together, our studies elucidated the mode of action of Lavendustin B analogs and provided a path for their further development as a new promising class of HIV-1 integrase inhibitors.
  28. Cancian M, Loreto E. A Mos1 transposase in vivo assay to screen new HIV-1 integrase inhibitors. Genetica. 2018;146:243-247 pubmed publisher
  29. Blanco J, Whitlock G, Milinkovic A, Moyle G. HIV integrase inhibitors: a new era in the treatment of HIV. Expert Opin Pharmacother. 2015;16:1313-24 pubmed publisher
    b>Integrase inhibitors (INIs) are the latest class of antiretroviral drugs approved for the treatment of HIV infection and are becoming 'standard' drugs in the treatment of both naïve as well as heavily pretreated individuals with HIV...
  30. Shen L, Peterson S, Sedaghat A, McMahon M, Callender M, Zhang H, et al. Dose-response curve slope sets class-specific limits on inhibitory potential of anti-HIV drugs. Nat Med. 2008;14:762-6 pubmed publisher
    ..Nucleoside reverse transcriptase inhibitors and integrase inhibitors have slopes of approximately 1, characteristic of noncooperative reactions, whereas non-nucleoside reverse ..
  31. Gianotti N, Poli A, Nozza S, Galli L, Galizzi N, Ripa M, et al. Durability of switch regimens based on rilpivirine or on integrase inhibitors, both in association with tenofovir and emtricitabine, in HIV-infected, virologically suppressed patients. BMC Infect Dis. 2017;17:723 pubmed publisher
    ..64-0.94; p = 0.009), but not with treatment group (rilpivirine vs. InSTI). In our clinical practice, the durability of the two regimens was comparable and both showed a very low probability of VF. ..
  32. Shet A, Markowitz M. Transmitted multidrug resistant HIV-1: new and investigational therapeutic approaches. Curr Opin Investig Drugs. 2006;7:709-20 pubmed
  33. Shafer R. Human Immunodeficiency Virus Type 1 Drug Resistance Mutations Update. J Infect Dis. 2017;216:S843-S846 pubmed publisher
    ..reverse transcriptase inhibitors efavirenz and rilpivirine, ritonavir-boosted lopinavir, and the integrase inhibitors raltegravir and elvitegravir...
  34. Tietjen I, Gatonye T, Ngwenya B, Namushe A, Simonambanga S, Muzila M, et al. Croton megalobotrys Müll Arg. and Vitex doniana (Sweet): Traditional medicinal plants in a three-step treatment regimen that inhibit in vitro replication of HIV-1. J Ethnopharmacol. 2016;191:331-340 pubmed publisher
    ..against viruses harboring major resistance mutations to licensed protease, reverse-transcriptase, or integrase inhibitors. We report for the first time a three-step traditional HIV/AIDS regimen, used alone or in combination with ..
  35. Rimawi B, Johnson E, Rajakumar A, Tao S, Jiang Y, Gillespie S, et al. Pharmacokinetics and Placental Transfer of Elvitegravir, Dolutegravir, and Other Antiretrovirals during Pregnancy. Antimicrob Agents Chemother. 2017;61: pubmed publisher
    The integrase inhibitors elvitegravir (EVG) and dolutegravir (DTG) rapidly decrease the plasma HIV-1 viral load, a key factor in the prevention of maternal-to-fetal transmission of HIV-1...
  36. Yang Z, Mueser T, Bushman F, Hyde C. Crystal structure of an active two-domain derivative of Rous sarcoma virus integrase. J Mol Biol. 2000;296:535-48 pubmed
    ..The observed asymmetric arrangement of C domains suggests that they could form a rotationally symmetric tetramer that may be important for bridging integrase complexes at each cDNA end...
  37. Phan A, Kuryavyi V, Ma J, Faure A, Andreola M, Patel D. An interlocked dimeric parallel-stranded DNA quadruplex: a potent inhibitor of HIV-1 integrase. Proc Natl Acad Sci U S A. 2005;102:634-9 pubmed
    ..on loop-modified sequences allowed us to propose a strategy toward the potential design of improved HIV-1 integrase inhibitors. Finally, we propose a model, based on molecular docking approaches, for positioning the 93del dimeric DNA ..
  38. Dreyfus D. Autoimmune disease: A role for new anti-viral therapies?. Autoimmun Rev. 2011;11:88-97 pubmed publisher
    ..topics in the pubmed data-base are reviewed suggesting that novel anti-viral agents such as retroviral integrase inhibitors, gene silencing therapies and eventually vaccines may provide new options for anti-viral therapy of ..
  39. Wlodawer A. Crystal structures of catalytic core domains of retroviral integrases and role of divalent cations in enzymatic activity. Adv Virus Res. 1999;52:335-50 pubmed
    ..Here the role of divalent cations in the enzymatic activity of IN and the search for inhibitors of this enzyme are discussed. ..
  40. Serrano Villar S, Sainz T, Ma Z, Utay N, Chun T, Wook Chun T, et al. Effects of Combined CCR5/Integrase Inhibitors-Based Regimen on Mucosal Immunity in HIV-Infected Patients Naïve to Antiretroviral Therapy: A Pilot Randomized Trial. PLoS Pathog. 2016;12:e1005381 pubmed publisher
  41. Firley D, Courcot B, Gillet J, Fraisse B, Zouhiri F, Desmaele D, et al. Experimental/theoretical electrostatic properties of a styrylquinoline-type HIV-1 integrase inhibitor and its progenitors. J Phys Chem B. 2006;110:537-47 pubmed
    ..The electrostatic potential minima in zwitterionic and nonzwitterionic forms of 1 are discussed in relation with the localization of possible metal chelation sites. ..
  42. de Mendoza C, Anta L, Garcia F, Pérez Elías M, Gutierrez F, Llibre J, et al. HIV-1 genotypic drug resistance interpretation rules - 2009 Spanish guidelines. AIDS Rev. 2009;11:39-51 pubmed
  43. Lisi L, Pizzoferrato M, Miscioscia F, Topai A, Navarra P. Interactions between integrase inhibitors and human arginase 1. J Neurochem. 2017;142:153-159 pubmed publisher
    ..Overall evidence shows that Dolutegravir, Raltegravir and Elvitegravir inhibit ARG activity. ..
  44. Brado D, Obasa A, Ikomey G, Cloete R, Singh K, Engelbrecht S, et al. Analyses of HIV-1 integrase sequences prior to South African national HIV-treatment program and available of integrase inhibitors in Cape Town, South Africa. Sci Rep. 2018;8:4709 pubmed publisher
    ..Our data suggest the prevalence of InSTI RAMs, against InSTIs, is low in South Africa, but natural polymorphisms and subtype-specific differences may influence the effect of individual treatment regimens. ..
  45. Hileman C, Funderburg N. Inflammation, Immune Activation, and Antiretroviral Therapy in HIV. Curr HIV/AIDS Rep. 2017;14:93-100 pubmed publisher
    ..In one ART initiation trial, integrase inhibitors appear to reduce inflammation to a greater degree than non-nucleoside reverse transcriptase inhibitors (..
  46. Spearman P. HIV-1 Gag as an Antiviral Target: Development of Assembly and Maturation Inhibitors. Curr Top Med Chem. 2016;16:1154-66 pubmed
    ..series of antiviral compounds, including those that specifically target CA-SP1 cleavage and the allosteric integrase inhibitors that inhibit maturation by a completely different mechanism...
  47. Shimura K, Kodama E, Sakagami Y, Matsuzaki Y, Watanabe W, Yamataka K, et al. Broad antiretroviral activity and resistance profile of the novel human immunodeficiency virus integrase inhibitor elvitegravir (JTK-303/GS-9137). J Virol. 2008;82:764-74 pubmed
  48. Mulu A, Maier M, Liebert U. Lack of integrase inhibitors associated resistance mutations among HIV-1C isolates. J Transl Med. 2015;13:377 pubmed publisher
    Although biochemical analysis of HIV-1 integrase enzyme suggested the use of integrase inhibitors (INIs) against HIV-1C, different viral subtypes may favor different mutational pathways potentially leading to varying levels of drug ..
  49. de Miguel R, Montejano R, Stella Ascariz N, Arribas J. A safety evaluation of raltegravir for the treatment of HIV. Expert Opin Drug Saf. 2018;17:217-223 pubmed publisher
  50. Faridoon -, Edkins A, Isaacs M, Mnkandhla D, Hoppe H, Kaye P. Synthesis and evaluation of substituted 4-(N-benzylamino)cinnamate esters as potential anti-cancer agents and HIV-1 integrase inhibitors. Bioorg Med Chem Lett. 2016;26:3810-2 pubmed publisher
    ..6?M) cell lines has been exhibited by a number of readily accessible 4-(N-benzylamino)cinnamate esters. The potential of the ligands as HIV-1 integrase inhibitors has also been examined.
  51. He H, Liu B, Zhang X, Chen W, Wang C. Development of a high-throughput assay for the HIV-1 integrase disintegration reaction. Sci China Life Sci. 2010;53:241-7 pubmed publisher
    ..The assay is sensitive and specific for the study of disintegration reaction as well as for the in vitro identification of antiviral drugs targeting IN, especially targeting IN-CCD. ..
  52. Penchala S, Fawcett S, Else L, Egan D, Amara A, Elliot E, et al. The development and application of a novel LC-MS/MS method for the measurement of Dolutegravir, Elvitegravir and Cobicistat in human plasma. J Chromatogr B Analyt Technol Biomed Life Sci. 2016;1027:174-80 pubmed publisher
    Dolutegravir and Elvitegravir belongs to a class of integrase inhibitors which has recently been approved by the FDA for the treatment of HIV-infection...
  53. Metifiot M, Johnson B, Kiselev E, Marler L, Zhao X, Burke T, et al. Selectivity for strand-transfer over 3'-processing and susceptibility to clinical resistance of HIV-1 integrase inhibitors are driven by key enzyme-DNA interactions in the active site. Nucleic Acids Res. 2016;44:6896-906 pubmed publisher
    ..The potency of integrase inhibitors against 3'-processing and their ability to overcome resistance is discussed.