WordNet
- limit, block, or decrease the action or function of; "inhibit the action of the enzyme"; "inhibit the rate of a chemical reaction"
- control and refrain from showing; of emotions, desires, impulses, or behavior (同)bottle up, suppress
- limit the range or extent of; "Contact between the young was inhibited by strict social customs"
- a substance that retards or stops an activity
PrepTutorEJDIC
- 〈感情・欲望・行動・作用など〉‘を'抑制する / (…しないように)〈人〉‘を'抑制する,妨げる《+『名』+『from』+『名』(do『ing』)》
- 抑制する人(物) / 化学反応抑制剤
Wikipedia preview
出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/08/23 15:42:44」(JST)
[Wiki en表示]
Integrase inhibitors (also known as integrase strand transfer inhibitors) are a class of antiretroviral drug designed to block the action of integrase, a viral enzyme that inserts the viral genome into the DNA of the host cell. Since integration is a vital step in retroviral replication, blocking it can halt further spread of the virus. Integrase inhibitors were initially developed for the treatment of HIV infection, but they could be applied to other retroviruses.
The first integrase inhibitor approved by the U.S. Food and Drug Administration (FDA) was raltegravir (brand name Isentress), approved on October 12, 2007. Research results published in the New England Journal of Medicine on July 24, 2008, concluded that "raltegravir plus optimized background therapy provided better viral suppression than optimized background therapy alone for at least 48 weeks."[1]
Since integrase inhibitors target a distinct step in the retroviral life cycle, they may be taken in combination with other types of HIV drugs to minimize adaptation by the virus. They are also useful in salvage therapy for patients whose virus has mutated and acquired resistance to other drugs.
Contents
- 1 Drugs in use and under development
- 1.1 Currently in use
- 1.2 Under development
- 2 References
- 3 External links
Drugs in use and under development[edit source | edit]
|
|
This section is outdated. Please update this article to reflect recent events or newly available information. (June 2013) |
Currently in use[edit source | edit]
- Elvitegravir (GS 9137 or JTK-303), licensed by Gilead Sciences from Japan Tobacco, after undergoing Phase 3 clinical trials,[2] was approved by the U.S. Food and Drug Administration on August 27, 2012 for use in adult patients starting HIV treatment for the first time as part of the fixed dose combination Stribild. Elvitegravir is a low-molecular-weight, highly selective integrase inhibitor that shares the core structure of quinolone antibiotics.[3]
Under development[edit source | edit]
- MK-2048, a second generation integrase inhibitor, that appears to have a duration of action up to 4 times longer than raltegravir.
References[edit source | edit]
- ^ Steigbigel RT, Cooper DA, Kumar PN, et al. (July 2008). "Raltegravir with optimized background therapy for resistant HIV-1 infection". N. Engl. J. Med. 359 (4): 339–54. doi:10.1056/NEJMoa0708975. PMID 18650512.
- ^ Gilead Press Release Phase III Clinical Trial of Elvitegravir July 22, 2008
- ^ AIDSinfo - HIV/AIDS Drug Information - GS 9137 (elvitegravir)
External links[edit source | edit]
- MK-0518, the first Integrase Inhibitor for HIV
- HIV Antiretroviral Agents in Development
- GS 9137 (elvitegravir) factsheet from NIH
- Savarino A (December 2006). "A historical sketch of the discovery and development of HIV-1 integrase inhibitors". Expert Opin Investig Drugs 15 (12): 1507–22. doi:10.1517/13543784.15.12.1507. PMID 17107277.
- IntegraseBookFull PDF
- integrase inhibitors at the US National Library of Medicine Medical Subject Headings (MeSH)
|
Pharmacology: enzyme inhibition
|
|
| Class |
- Competitive inhibition
- Uncompetitive inhibition
- Non-competitive inhibition
- Suicide inhibition
- Mixed inhibition
|
|
| Substrate |
| Oxidoreductase (EC 1) |
- 1.1 Aldose reductase
- HMG-CoA reductase
- 1.5 Dihydrofolate reductase
- 1.17 Xanthine oxidase
- Ribonucleotide reductase
|
|
| Transferase (EC 2) |
- 2.1 COMT
- Thymidylate synthase
- 2.5 Dihydropteroate synthetase
- Farnesyltransferase
- 2.7 Nucleotidyltransferase
- Integrase
- Reverse transcriptase
- Protein kinase
|
|
| Hydrolase (EC 3) |
- 3.1 Phosphodiesterase
- Acetylcholinesterase
- Ribonuclease
- 3.2 Polygalacturonase
- Neuraminidase
- Alpha-glucosidase
- 3.4 Protease: Exopeptidase
- Dipeptidyl peptidase-4
- ACE
- Endopeptidase
- Trypsin
- Renin
- Matrix metalloproteinase
- 3.5 Histone deacetylase
- Beta-lactamase
|
|
| Lyase (EC 4) |
|
|
|
|
Antiviral drugs: antiretroviral drugs used against HIV (primarily J05)
|
|
Entry/fusion inhibitors
(Discovery & development) |
- gp41 (Enfuvirtide)
- CCR5 (Maraviroc
- Vicriviroc†, Cenicriviroc†, PRO 140†)
- CD4 (Ibalizumab†)
|
|
Reverse-transcriptase
inhibitors (RTIs) |
|
Nucleoside &
nucleotide (NRTI)
|
- Nucleoside analogues/NARTIs: Abacavir (ABC)°#
- Emtricitabine (FTC)°#
- Lamivudine (3TC)°#
- Didanosine (ddI)#
- Zidovudine (AZT)#
- Apricitabine†
- Stampidine†
- Elvucitabine†
- Racivir†
- Amdoxovir†
- Stavudine (d4T)#
- Zalcitabine (ddC)◊
- Festinavir†
- Nucleotide analogues/NtRTIs: Tenofovir disoproxil fumarate (TDF)°#
- Tenofovir alafenamide fumarate (TAF)†
|
|
|
Non-nucleoside (NNRTI)
(Discovery & development)
|
- (1st generation) Efavirenz (EFV)°#
- Nevirapine (NVP)#
- Loviride◊
- Delavirdine (DLV)◊
(2nd generation) diarylpyrimidines (Etravirine- Rilpivirine)
- Lersivirine†
|
|
|
| Integrase inhibitors |
- Raltegravir°
- Elvitegravir
- Dolutegravir†
- Globoidnan A (experimental)
- MK-2048†
- BI 224436†
- GSK744†
|
|
| Maturation inhibitors |
|
|
Protease Inhibitors (PI)
(Discovery and development) |
|
1st generation
|
- Fosamprenavir°
- Lopinavir°#
- Nelfinavir#
- Ritonavir#
- Saquinavir#
- Amprenavir◊
- Indinavir◊#
|
|
|
2nd generation
|
- Atazanavir°
- Darunavir°
- Tipranavir
|
|
|
| Combined formulations |
- Lamivudine/zidovudine
- Emtricitabine/tenofovir/efavirenz
- Abacavir/lamivudine/zidovudine
- Tenofovir/emtricitabine
- Lopinavir/ritonavir
- Abacavir/lamivudine
- Emtricitabine/rilpivirine/tenofovir
- Elvitegravir/cobicistat/emtricitabine/tenofovir
|
|
| Experimental agents |
|
Uncoating inhibitors
|
|
|
|
Transcription inhibitors
|
|
|
|
Translation inhibitors
|
|
|
|
Other
|
- Abzyme
- Calanolide A
- Ceragenin
- Cyanovirin-N
- Diarylpyrimidines
- Epigallocatechin gallate (EGCG)
- Foscarnet
- Griffithsin
- Hydroxycarbamide
- Miltefosine
- Portmanteau inhibitors
- Seliciclib†
- Synergistic enhancers
- Tre recombinase
- Zinc finger protein transcription factor
- KP-1461†
- Cobicistat†
|
|
|
Failed agents
|
- Dexelvucitabine
- Capravirine
- Emivirine
- Lodenosine
- Atevirdine
- Brecanavir
- Aplaviroc
|
|
|
- #WHO-EM
- ‡Withdrawn from market
- Clinical trials:
- †Phase III
- §Never to phase III
°DHHS preferred first-line agent. ◊Formerly or rarely used agent.
|
|
|
cutn/syst (hppv/hiva, infl/zost/zoon)/epon
|
drug (dnaa, rnaa, rtva, vacc)
|
|
|
|
UpToDate Contents
全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.
English Journal
- Plasma concentrations of efavirenz, darunavir/ritonavir and raltegravir in HIV-HCV-coinfected patients without liver cirrhosis in comparison with HIV-monoinfected patients.
- Calza L1, Danese I, Colangeli V, Manfredi R, Magistrelli E, Verucchi G, Conti M, Motta R, Viale P.
- Infectious diseases (London, England).Infect Dis (Lond).2015 Sep;47(9):625-36. doi: 10.3109/23744235.2015.1034169. Epub 2015 Apr 15.
- BACKGROUND: The objective of the study was to assess plasma concentrations of efavirenz, darunavir/ritonavir and raltegravir in patients with human immunodeficiency virus-hepatitis C virus (HIV-HCV)-coinfection without liver cirrhosis.METHODS: In this observational, open-label study, adult HIV-infec
- PMID 25875396
- A rare case of immune reconstitution inflammatory syndrome presenting as secondary syphilis.
- Khatri A1, Skalweit MJ2.
- International journal of STD & AIDS.Int J STD AIDS.2015 Sep;26(10):749-51. doi: 10.1177/0956462414553013. Epub 2014 Oct 13.
- Immune reconstitution syndrome has rarely been reported in the context of syphilis infection. We report a patient with AIDS (CD4 42 cells/mm(3), viral load 344,000 cp/ml), treated previously for secondary syphilis and started on an integrase inhibitor-based single-tablet antiretroviral treatment reg
- PMID 25311145
- Changes in Inflammation and Immune Activation With Atazanavir-, Raltegravir-, Darunavir-Based Initial Antiviral Therapy: ACTG 5260s.
- Kelesidis T1, Tran TT2, Stein JH3, Brown TT4, Moser C2, Ribaudo HJ2, Dube MP5, Murphy R6, Yang OO1, Currier JS1, McComsey GA7.
- Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.Clin Infect Dis.2015 Aug 15;61(4):651-60. doi: 10.1093/cid/civ327. Epub 2015 Apr 22.
- BACKGROUND: It is unclear whether the integrase inhibitor raltegravir (RAL) reduces inflammation and immune activation compared with ritonavir-boosted protease inhibitors (PIs).METHODS: In a prospective, randomized, multicenter clinical trial that included 328 human immunodeficiency type 1 (HIV-1)-i
- PMID 25904376
Japanese Journal
- Use of a Hexasubstituted Benzene Scaffold in the Development of Multivalent HIV-1 Integrase Inhibitors
- Tupchiangmai Wipa,Choksakulporn Saowanaporn,Tewtrakul Supinya [他]
- Chemical and pharmaceutical bulletin 62(8), 754-763, 2014-08
- NAID 40020136534
- Use of a Hexasubstituted Benzene Scaffold in the Development of Multivalent HIV-1 Integrase Inhibitors
- , , , ,
- Chemical and Pharmaceutical Bulletin 62(8), 754-763, 2014
- … The highly directional hexasubstituted benzene moiety was used as the central scaffold to create new human immunodeficiency virus (HIV)-1 integrase inhibitors through the attachment of multiple active groups. …
- NAID 130004677382
Related Links
- From Isentress in 2007 to Tivicay just last month, integrase inhibitors have had a huge impact on our HIV treatment options. ... The first integrase inhibitor for HIV treatment, raltegravir (Isentress), has been used for different ...
- Abstract Raltegravir is the first approved human immunodeficiency virus type 1 (HIV-1) integrase inhibitor; it targets the strand transfer step of HIV-1 integration. Clinical trials have demonstrated that raltegravir-containing ...
Related Pictures
★リンクテーブル★
[★]
- 英
- integrase inhibitor
- 関
- インテグラーゼ阻害薬
[★]
- 英
- integrase inhibitor
- 関
- インテグラーゼ阻害剤
[★]
HIVインテグラーゼ阻害薬、HIVインテグラーゼ阻害剤
[★]
- 関
- abrogate、block、depress、depression、deter、inhibition、interdict、prevent、prevention、repress、repression、restrain、restraint、suppress、suppression
[★]
- 関
- blocker、depressant、suppressant
[★]
インテグラーゼ、組込み酵素