HIV protease inhibitor

• HIVプロテアーゼ阻害薬、HIVプロテアーゼ阻害剤

WordNet

1. limit, block, or decrease the action or function of; "inhibit the action of the enzyme"; "inhibit the rate of a chemical reaction"
2. control and refrain from showing; of emotions, desires, impulses, or behavior (同)bottle up, suppress
3. limit the range or extent of; "Contact between the young was inhibited by strict social customs"
4. a substance that retards or stops an activity
5. the 8th letter of the Roman alphabet (同)h
6. any enzyme that catalyzes the splitting of proteins into smaller peptide fractions and amino acids by a process known as proteolysis (同)peptidase, proteinase, proteolytic_enzyme
7. infection by the human immunodeficiency virus

PrepTutorEJDIC

1. 〈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』)》
2. 抑制する人(物) / 化学反応抑制剤
3. hydrogenの化学記号
4. 鉛筆の硬度 / 《俗》heroin

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/08/17 04:15:47」(JST)

wiki en

[Wiki en表示]

For natural protease inhibitors, see protease inhibitor (biology).

Protease inhibitors (PIs) are a class of antiviral drugs that are widely used to treat HIV/AIDS and hepatitis caused by hepatitis C virus. Protease inhibitors prevent viral replication by selectively binding to viral proteases (e.g. HIV-1 protease) and blocking proteolytic cleavage of protein precursors that are necessary for the production of infectious viral particles.

Protease inhibitors have been developed or are presently undergoing testing for treating various viruses:

• HIV/AIDS: antiretroviral protease inhibitors (saquinavir, ritonavir, indinavir, nelfinavir, amprenavir etc.)
• Hepatitis C: boceprevir, telaprevir

Given the specificity of the target of these drugs there is the risk, as in antibiotics, of the development of drug-resistant mutated viruses. To reduce this risk it is common to use several different drugs together that are each aimed at different targets.

Antiretrovirals

Protease inhibitors were the second class of antiretroviral drugs developed. The first members of this class, saquinavir (Hoffman-La Roche) and ritonovir (Abbott), were approved in late 1995-1996. Within 2 years, annual deaths from AIDS in the United States fell from over 50,000 to approximately 18,000 Prior to this the annual death rate had been increasing by approximately 20% each year.

Name	Trade name	Company	Patent	Notes
Saquinavir	Fortovase, Invirase	Hoffmann–La Roche	U.S. Patent 5,196,438	It was the first protease inhibitor approved by the FDA (December 6, 1995).
Ritonavir	Norvir	Abbott Laboratories	U.S. Patent 5,541,206	-
Indinavir	Crixivan	Merck & Co.	U.S. Patent 5,413,999	-
Nelfinavir	Viracept	Agouron Pharmaceuticals	U.S. Patent 5,484,926	-
Amprenavir	Agenerase	GlaxoSmithKline	U.S. Patent 5,585,397	The FDA approved it April 15, 1999, making it the sixteenth FDA-approved antiretroviral. It was the first protease inhibitor approved for twice-a-day dosing instead of needing to be taken every eight hours. The convenient dosing came at a price, as the dose required is 1,200 mg, delivered in eight very large gel capsules. Production was discontinued by the manufacturer December 31, 2004, as it has been superseded by fosamprenavir.
Lopinavir	Kaletra	Abbott	U.S. Patent 5,914,332	Is only marketed as a combination, with ritonavir.
Atazanavir	Reyataz	Bristol-Myers Squibb	U.S. Patent 5,849,911	The FDA approved it on June 20, 2003. Atazanavir was the first PI approved for once-daily dosing. It appears to be less likely to cause lipodystrophy and elevated cholesterol as side effects. It may also not be cross-resistant with other PIs.
Fosamprenavir	Lexiva, Telzir	GlaxoSmithKline	-	Is a prodrug of amprenavir. The FDA approved it October 20, 2003. The human body metabolizes fosamprenavir in order to form amprenavir, which is the active ingredient. That metabolization increases the duration that amprenavir is available, making fosamprenavir a slow-release version of amprenavir and thus reduces the number of pills required versus standard amprenavir.
Tipranavir	Aptivus	Boehringer-Ingelheim	-	Also known as tipranavir disodium
Darunavir	Prezista	Tibotec	U.S. Patent 6,248,775	It was approved by the Food and Drug Administration (FDA) on June 23, 2006. Prezista is an OARAC recommended treatment option for treatment-naïve and treatment-experienced adults and adolescents. Several ongoing phase III trials are showing a high efficiency for the PREZISTA/rtv combination being superior to the lopinavir/rtv combination for first-line therapy. Darunavir is the first drug in a long time that didn't come with a price increase. It leapfrogged two other approved drugs of its type, and is matching the price of a third.
Simeprevir	Olysio, formerly TMC435	Medivir & Johnson & Johnson	U.S. Patent 7,671,032	Simeprevir is a NS3/4A protease inhibitor

Antiprotozoal activity

Researchers are investigating the use of protease inhibitors developed for HIV treatment as anti-protozoals for use against malaria and gastrointestinal protozoal infections:

• A combination of ritonavir and lopinavir was found to have some effectiveness against Giardia infection.
• The drugs saquinavir, ritonavir, and lopinavir have been found to have anti-malarial properties.
• A cysteine protease inhibitor drug was found to cure Chagas disease in mice.

Anticancer activity

Researchers are investigating whether protease inhibitors could possibly be used to treat cancer. For example, nelfinavir and atazanavir are able to kill tumor cells in culture (in a Petri dish). This effect has not yet been examined in humans; but studies in laboratory mice have shown that nelfinavir is able to suppress the growth of tumors in these animals, which represents a promising lead towards testing this drug in humans as well.

Inhibitors of the proteasome, such as Velcade/Bortezomib are now front-line drugs for the treatment of various cancers, notably Multiple Myeloma.

Side effects

Protease inhibitors can cause a syndrome of lipodystrophy, hyperlipidaemia, diabetes mellitus type 2, and kidney stones.

See also

• David Ho - AIDS researcher who pioneered the use of protease inhibitors in treating HIV-infected patients
• The Proteolysis Map
• Reverse transcriptase inhibitor

References

External links

• A brief history of the development of protease inhibitors by Hoffman La Roche, Abbott, and Merck

UpToDate Contents

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• 1. HIV感染症の治療に用いる抗レトロウイルス薬の概要 overview of antiretroviral agents used to treat hiv
• 2. 未治療HIV感染患者のための抗レトロウイルス療法の選択 selecting antiretroviral regimens for the treatment naive hiv infected patient
• 3. HIV薬剤耐性検査結果の解釈について interpretation of hiv drug resistance testing
• 4. HIV-2感染の治療 treatment of hiv 2 infection
• 5. 結晶誘発性急性腎障害 crystal induced acute kidney injury

English Journal

• Novel Approaches to Targeting Visceral and Hepatic Adiposities in HIV-Associated Lipodystrophy.

• Tien PC1,2.
• Current atherosclerosis reports.Curr Atheroscler Rep.2015 Dec;17(12):73. doi: 10.1007/s11883-015-0545-2.
• Visceral and hepatic adiposities have been associated with both cardiovascular and liver disease and are of concern in HIV-infected persons in the modern era of combination antiretroviral therapy (ART). The development of therapeutic targets to reduce visceral and hepatic adiposities in HIV-infected
• PMID 26493063

• PLGA-PEG Nanoparticles Coated with Anti-CD45RO and Loaded with HDAC Plus Protease Inhibitors Activate Latent HIV and Inhibit Viral Spread.

• Tang X1,2, Liang Y3, Liu X1, Zhou S1, Liu L1, Zhang F1, Xie C4, Cai S1, Wei J1, Zhu Y5, Hou W6.
• Nanoscale research letters.Nanoscale Res Lett.2015 Dec;10(1):413. doi: 10.1186/s11671-015-1112-z. Epub 2015 Oct 22.
• Activating HIV-1 proviruses in latent reservoirs combined with inhibiting viral spread might be an effective anti-HIV therapeutic strategy. Active specific delivery of therapeutic drugs into cells harboring latent HIV, without the use of viral vectors, is a critical challenge to this objective. In t
• PMID 26489856

• Maraviroc Pharmacokinetics in HIV-1-Infected Pregnant Women.

• Colbers A1, Best B2, Schalkwijk S3, Wang J4, Stek A5, Hidalgo Tenorio C6, Hawkins D7, Taylor G8, Kreitchmann R9, Burchett S10, Haberl A11, Kabeya K12, van Kasteren M13, Smith E14, Capparelli E2, Burger D1, Mirochnick M15; PANNA Network and the IMPAACT 1026 Study Team.
• Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.Clin Infect Dis.2015 Nov 15;61(10):1582-9. doi: 10.1093/cid/civ587. Epub 2015 Jul 22.
• OBJECTIVE: To describe the pharmacokinetics of maraviroc in human immunodeficiency virus (HIV)-infected women during pregnancy and post partum.METHODS: HIV-infected pregnant women receiving maraviroc as part of clinical care had intensive steady-state 12-hour pharmacokinetic profiles performed durin
• PMID 26202768

Japanese Journal

• The Effect of the Different Treatment Protocols on Virological and Immunological Responses in Patients with HIV/AIDS

• Japanese Journal of Infectious Diseases 67(5), 339-344, 2014
• NAID 130004692231

• 3P020 触媒アスパラギン酸の電荷改変によるHIV-1プロテアーゼの分子動力学シミュレーションへの影響(01A.蛋白質:構造,ポスター,日本生物物理学会年会第51回(2013年度))

• 生物物理 53(SUPPLEMENT_1-2), S215, 2013-09-13
• NAID 110009819824

• Oxamide Replacement in Pseudo-Symmetric HIV Protease Inhibitor Involving Multiple Bridging Water Molecules

• Peptide science : proceedings of the ... Japanese Peptide Symposium 2012, 271-272, 2013-03-01
• NAID 10031161625

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★リンクテーブル★

リンク元	「HIVプロテアーゼ阻害剤」「HIVプロテアーゼ阻害薬」
拡張検索	「HIV protease inhibitors」
関連記事	「inhibit」「inhibitor」「HIV」「H」「protease inhibitor」

「HIVプロテアーゼ阻害剤」

　　[★]

英

HIV protease inhibitor

関

HIVプロテアーゼ阻害薬

「HIVプロテアーゼ阻害薬」

　　[★]

英

HIV protease inhibitor

関

HIVプロテアーゼ阻害剤

「HIV protease inhibitors」

　　[★]

関

Protease inhib- itors)

「inhibit」

　　[★]

• v.

• 抑制する、阻害する、阻止する

関

abrogate、block、depress、depression、deter、inhibition、interdict、prevent、prevention、repress、repression、restrain、restraint、suppress、suppression

　 　 　 　

「inhibitor」

　　[★]

• n.

• 阻害剤、阻害薬、抑制薬、抑制剤、(内在性物質について)インヒビター、抑制物質

関

blocker、depressant、suppressant

　 　

「HIV」

　　[★] human immunodeficiency virus HIVウイルス ヒト免疫不全ウイルス 　

「H」

　　[★]

• 食道裂孔
• ヒスチジン
• 水素

　 　 　

「protease inhibitor」

　　[★]

関

specific agents

同

PI