https://www.wikidoc.org/index.php?title=Bevirimat&feed=atom&action=historyBevirimat - Revision history2024-03-28T21:44:43ZRevision history for this page on the wikiMediaWiki 1.40.0https://www.wikidoc.org/index.php?title=Bevirimat&diff=711118&oldid=prevWikiBot: Robot: Automated text replacement (-{{WikiDoc Cardiology Network Infobox}} +, -<references /> +{{reflist|2}}, -{{reflist}} +{{reflist|2}})2012-09-04T14:45:38Z<p>Robot: Automated text replacement (-{{WikiDoc Cardiology Network Infobox}} +, -<references /> +{{reflist|2}}, -{{reflist}} +{{reflist|2}})</p>
<p><b>New page</b></p><div>{{Drugbox<br />
| IUPAC_name = 3β-(3-carboxy-3-methyl -butanoyloxy)lup-20(29)- en-28-oic acid<br />
| image = Bevirimat.svg<br />
| CAS_number = 174022-42-5<br />
| ATC_prefix = <br />
| ATC_suffix = <br />
| PubChem = 457928<br />
| DrugBank = <br />
| C=36|H=56|O=6<br />
| molecular_weight = 584.826 g/mol<br />
| smiles = CC(=C)C1CCC2(C1C3CCC4C5(CCC(C(C5CCC4(C3(CC2)C)C)(C)C)OC(=O)CC(C)(C)C(=O)O)C)C(=O)O<br />
| synonyms = PA-457, 3-O-(3',3'-dimethylsuccinyl)- [[betulinic acid]]<br />
| bioavailability = <br />
| protein_bound = <br />
| metabolism = [[Liver|Hepatic]] [[glucuronidation]] ([[Glucuronosyltransferase|UGT1A3]]-mediated)<br />
| elimination_half-life = 56.3 to 69.5 hours<br />
| excretion = <br />
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --><br />
| pregnancy_US = <!-- A / B / C / D / X --><br />
| pregnancy_category= <br />
| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 --><br />
| legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII --><br />
| legal_UK = <!-- GSL / P / POM / CD / Class A, B, C --><br />
| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V --><br />
| legal_status = <br />
| routes_of_administration = Oral<br />
}}<br />
'''Bevirimat''' is a anti-HIV drug derived from a [[betulinic acid]]-like compound, first isolated from ''[[Syzygium]] claviflorum,'' a Chinese herb. It is believed to inhibit [[HIV]] by a novel mechanism, so-called maturation inhibition. <ref>Smith PF, Ogundele A, Forrest A, Wilton J, Salzwedel K, Doto J, Allaway GP, Martin DE. ''Phase I and II study of the safety, virologic effect, and pharmacokinetics/pharmacodynamics of single-dose 3-o-(3',3'-dimethylsuccinyl)betulinic acid (bevirimat) against human immunodeficiency virus infection.'' Antimicrob Agents Chemother. 2007 Oct;51(10):3574-81. Epub 2007 Jul 16. PMID 17638699</ref> It is not currently [[FDA]]-approved, but is undergoing [[clinical trials]] conducted by the pharmaceutical company [[Panacos Pharmaceuticals|Panacos]]. <br />
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==Clinical trials==<br />
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In December 2007, some results of the [[Phase IIb|Phase IIb trial]] were released. Thomson Financial News reported that, "some patients respond 'very well' to the drug, while another population 'does not respond as well at current dose levels.'" Panacos said it intends to add a group to the study at a higher dosage.<ref>Zhou, Wanfeng. [http://money.cnn.com/news/newsfeeds/articles/newstex/AFX-0013-21570015.htm Panacos: Bevirimat data support further dose escalation.] Thomson Financial News. 10 Dec 2007.</ref> <br />
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==Pharmacokinetics==<br />
According to the only currently available study, "the mean terminal [[elimination half-life]] of bevirimat ranged from 56.3 to 69.5 hours, and the mean [[Clearance (medicine)|clearance]] ranged from 173.9 to 185.8 mL/hour." <ref>{{cite journal |author=Martin DE, Blum R, Doto J, Galbraith H, Ballow C |title=Multiple-dose pharmacokinetics and safety of bevirimat, a novel inhibitor of HIV maturation, in healthy volunteers |journal=Clin Pharmacokinet |volume=46 |issue=7 |pages=589–98 |year=2007 |pmid=17596104 |doi=}}</ref><br />
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==Mechanism of action==<br />
Bevirimat targets the [[HIV_structure_and_genome#Gag|gag]] polyprotein precursor, the main structural protein responsible for assembly and budding of virion particles.<ref>{{cite journal |author=Salzwedel K, Martin DE, Sakalian M |title=Maturation inhibitors: a new therapeutic class targets the virus structure |journal=AIDS Rev |volume=9 |issue=3 |pages=162–72 |year=2007 |pmid=17982941 |doi=}}</ref> By binding to the gag polyprotein, bevirimat prevents its cleavage by the protease enzyme into functional subunits. Unlike the protease inhibitors, bevirimat binds the gag protein, not the protease enzyme. The resulting virus particles are structurally defective and are incapable of spreading infection around the body.<ref>[http://www.panacos.com/product_2.htm bevirimat (PA-457)]. Panacos Pharmaceuticals Inc. accessed 28 Dec 2007.</ref> For unknown reasons, [[Protease inhibitor (pharmacology)|protease inhibitor]]-resistant HIV-1 was hypersensitive to bevirimat [[in vitro]].<ref>{{cite journal |author=Stoddart CA, Joshi P, Sloan B, ''et al'' |title=Potent Activity of the HIV-1 Maturation Inhibitor Bevirimat in SCID-hu Thy/Liv Mice |journal=PLoS ONE |volume=2 |issue=11 |pages=e1251 |year=2007 |pmid=18043758 |doi=10.1371/journal.pone.0001251 |url=http://www.plosone.org/article/info:doi/10.1371/journal.pone.0001251}}</ref><br />
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==External links==<br />
*[http://www.panacos.com/documents/panacosmovie.html An animation illustrating Bevirimat's mechanism of action]<br />
*[http://www.panacos.com/product_2.htm Overview and Publication Listing for Bevirimat from Panacos]<br />
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==References==<br />
{{reflist|2}}<br />
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==External links==<br />
*[http://www.aidsmeds.com/archive/bevirimat_1897.shtml AIDSmeds Bevirimat]<br />
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{{HIVpharm}}<br />
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[[Category:Maturation inhibitors]]</div>WikiBot