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Bevirimat



Bevirimat
Systematic (IUPAC) name
3β-(3-carboxy-3-methyl -butanoyloxy)lup-20(29)- en-28-oic acid
Identifiers
CAS number 174022-42-5
ATC code  ?
PubChem 457928
Chemical data
Formula C36H56O6 
Mol. mass 584.826 g/mol
SMILES search in eMolecules, PubChem
Synonyms PA-457, 3-O-(3',3'-dimethylsuccinyl)- betulinic acid
Pharmacokinetic data
Bioavailability  ?
Metabolism Hepatic glucuronidation (UGT1A3-mediated)
Half life 56.3 to 69.5 hours
Excretion  ?
Therapeutic considerations
Pregnancy cat.

?

Legal status
Routes Oral

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. [1] It is not currently FDA-approved, but is undergoing clinical trials conducted by the pharmaceutical company Panacos.

Additional recommended knowledge

Contents

Clinical trials

In December 2007, some results of the 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.[2]

Pharmacokinetics

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 ranged from 173.9 to 185.8 mL/hour." [3]

Mechanism of action

Bevirimat targets the gag polyprotein precursor, the main structural protein responsible for assembly and budding of virion particles.[4] 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.[5] For unknown reasons, protease inhibitor-resistant HIV-1 was hypersensitive to bevirimat in vitro.[6]

References

  1. ^ 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
  2. ^ Zhou, Wanfeng. Panacos: Bevirimat data support further dose escalation. Thomson Financial News. 10 Dec 2007.
  3. ^ Martin DE, Blum R, Doto J, Galbraith H, Ballow C (2007). "Multiple-dose pharmacokinetics and safety of bevirimat, a novel inhibitor of HIV maturation, in healthy volunteers". Clin Pharmacokinet 46 (7): 589–98. PMID 17596104.
  4. ^ Salzwedel K, Martin DE, Sakalian M (2007). "Maturation inhibitors: a new therapeutic class targets the virus structure". AIDS Rev 9 (3): 162–72. PMID 17982941.
  5. ^ bevirimat (PA-457). Panacos Pharmaceuticals Inc. accessed 28 Dec 2007.
  6. ^ Stoddart CA, Joshi P, Sloan B, et al (2007). "Potent Activity of the HIV-1 Maturation Inhibitor Bevirimat in SCID-hu Thy/Liv Mice". PLoS ONE 2 (11): e1251. doi:10.1371/journal.pone.0001251. PMID 18043758.
 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Bevirimat". A list of authors is available in Wikipedia.
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