Bevirimat
Identification
- Generic Name
- Bevirimat
- DrugBank Accession Number
- DB06581
- Background
Bevirimat, also known as PA-457 or YK-FH312, is investigated in clinical trials for treating HIV infection. Bevirimat is a solid. This compound belongs to the androgens and derivatives, which are hydroxylated C19 steroid hormones. They are known to favour the development of masculine characteristics. They also show profound effects on scalp and body hair in humans. Bevirimat targets the protein gag-pol polyprotein. Bevirimat is derived from a betulinic acid-like compound, first isolated from Syzygium claviflorum, a Chinese herb. It is not currently FDA-approved, but is undergoing clinical trials conducted by the pharmaceutical company Panacos.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
- Weight
- Average: 584.8262
Monoisotopic: 584.407689524 - Chemical Formula
- C36H56O6
- Synonyms
- Bevirimat
- External IDs
- MPC-4326
- PA-457
- YK-FH312
Pharmacology
- Indication
Investigated for use/treatment in HIV infection.
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- Pharmacodynamics
Not Available
- Mechanism of action
Bevirimat has a novel mechanism of action, specifically inhibiting cleavage of spacer peptide 1 (SP1) from the C-terminus of capsid which results in defective core condensation. Specifically, bevirimat binds at the SP1/capsid junction, preventing cleavage by HIV protease.
Target Actions Organism UGag-Pol polyprotein Not Available - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
Hepatic glucuronidation (UGT1A3-mediated)
- Route of elimination
Not Available
- Half-life
56.3 to 69.5 hours
- Clearance
Not Available
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- Not Available
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as triterpenoids. These are terpene molecules containing six isoprene units.
- Kingdom
- Organic compounds
- Super Class
- Lipids and lipid-like molecules
- Class
- Prenol lipids
- Sub Class
- Triterpenoids
- Direct Parent
- Triterpenoids
- Alternative Parents
- 18-hydroxysteroids / Oxosteroids / Tricarboxylic acids and derivatives / Fatty acid esters / Carboxylic acid esters / Carboxylic acids / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
- Substituents
- 18-hydroxysteroid / 18-oxosteroid / Aliphatic homopolycyclic compound / Carbonyl group / Carboxylic acid / Carboxylic acid derivative / Carboxylic acid ester / Fatty acid ester / Fatty acyl / Hydrocarbon derivative
- Molecular Framework
- Aliphatic homopolycyclic compounds
- External Descriptors
- dicarboxylic acid monoester, monocarboxylic acid, pentacyclic triterpenoid (CHEBI:65484)
- Affected organisms
- Human Immunodeficiency Virus
Chemical Identifiers
- UNII
- S125DW66N8
- CAS number
- 174022-42-5
- InChI Key
- YJEJKUQEXFSVCJ-WRFMNRASSA-N
- InChI
- InChI=1S/C36H56O6/c1-21(2)22-12-17-36(30(40)41)19-18-34(8)23(28(22)36)10-11-25-33(7)15-14-26(42-27(37)20-31(3,4)29(38)39)32(5,6)24(33)13-16-35(25,34)9/h22-26,28H,1,10-20H2,2-9H3,(H,38,39)(H,40,41)/t22-,23+,24-,25+,26-,28+,33-,34+,35+,36-/m0/s1
- IUPAC Name
- (1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-9-[(3-carboxy-3,3-dimethylpropanoyl)oxy]-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-icosahydro-1H-cyclopenta[a]chrysene-3a-carboxylic acid
- SMILES
- [H][C@]12[C@@H](CC[C@@]1(CC[C@]1(C)[C@]2([H])CC[C@]2([H])[C@@]3(C)CC[C@H](OC(=O)CC(C)(C)C(O)=O)C(C)(C)[C@]3([H])CC[C@@]12C)C(O)=O)C(C)=C
References
- General References
- Stoddart CA, Joshi P, Sloan B, Bare JC, Smith PC, Allaway GP, Wild CT, Martin DE: Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice. PLoS One. 2007 Nov 28;2(11):e1251. [Article]
- Adamson CS, Ablan SD, Boeras I, Goila-Gaur R, Soheilian F, Nagashima K, Li F, Salzwedel K, Sakalian M, Wild CT, Freed EO: In vitro resistance to the human immunodeficiency virus type 1 maturation inhibitor PA-457 (Bevirimat). J Virol. 2006 Nov;80(22):10957-71. Epub 2006 Sep 6. [Article]
- 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. [Article]
- External Links
- PubChem Compound
- 457928
- PubChem Substance
- 175427073
- ChemSpider
- 403003
- BindingDB
- 50050955
- ChEBI
- 65484
- ChEMBL
- CHEMBL404519
- ZINC
- ZINC000003936686
- PDBe Ligand
- 2I4
- Wikipedia
- Bevirimat
- PDB Entries
- 7r7p
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 2 Completed Treatment Human Immunodeficiency Virus (HIV) Infections 2 2 Completed Treatment Human Immunodeficiency Virus Type 1 (HIV-1) Infection 1 2 Terminated Treatment Human Immunodeficiency Virus (HIV) Infections 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.000135 mg/mL ALOGPS logP 5.88 ALOGPS logP 8 Chemaxon logS -6.6 ALOGPS pKa (Strongest Acidic) 4.16 Chemaxon pKa (Strongest Basic) -7.1 Chemaxon Physiological Charge -2 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 100.9 Å2 Chemaxon Rotatable Bond Count 7 Chemaxon Refractivity 161.75 m3·mol-1 Chemaxon Polarizability 67.97 Å3 Chemaxon Number of Rings 5 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9113 Blood Brain Barrier + 0.7711 Caco-2 permeable + 0.5417 P-glycoprotein substrate Substrate 0.7828 P-glycoprotein inhibitor I Inhibitor 0.5376 P-glycoprotein inhibitor II Inhibitor 0.8093 Renal organic cation transporter Non-inhibitor 0.7973 CYP450 2C9 substrate Non-substrate 0.8472 CYP450 2D6 substrate Non-substrate 0.9272 CYP450 3A4 substrate Substrate 0.7933 CYP450 1A2 substrate Non-inhibitor 0.8733 CYP450 2C9 inhibitor Non-inhibitor 0.8726 CYP450 2D6 inhibitor Non-inhibitor 0.9514 CYP450 2C19 inhibitor Non-inhibitor 0.9112 CYP450 3A4 inhibitor Non-inhibitor 0.7177 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7885 Ames test Non AMES toxic 0.8579 Carcinogenicity Non-carcinogens 0.9403 Biodegradation Not ready biodegradable 0.9835 Rat acute toxicity 3.5488 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9294 hERG inhibition (predictor II) Non-inhibitor 0.8177
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 244.983026 predictedDarkChem Lite v0.1.0 [M-H]- 221.75883 predictedDeepCCS 1.0 (2019) [M+H]+ 245.753026 predictedDarkChem Lite v0.1.0 [M+H]+ 223.75267 predictedDeepCCS 1.0 (2019) [M+Na]+ 246.164726 predictedDarkChem Lite v0.1.0 [M+Na]+ 229.96564 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Not Available
- Pharmacological action
- Unknown
- General Function
- Zinc ion binding
- Specific Function
- Gag-Pol polyprotein: Mediates, with Gag polyrotein, the essential events in virion assembly, including binding the plasma membrane, making the protein-protein interactions necessary to create spher...
- Gene Name
- gag-pol
- Uniprot ID
- P04585
- Uniprot Name
- Gag-Pol polyprotein
- Molecular Weight
- 162041.05 Da
References
- Stoddart CA, Joshi P, Sloan B, Bare JC, Smith PC, Allaway GP, Wild CT, Martin DE: Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice. PLoS One. 2007 Nov 28;2(11):e1251. [Article]
Drug created at March 19, 2008 16:37 / Updated at February 21, 2021 18:52