Bevirimat

Identification

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Name
Bevirimat
Accession Number
DB06581
Type
Small Molecule
Groups
Investigational
Description

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.

Structure
Thumb
Synonyms
  • bevirimat
External IDs
MPC-4326 / PA-457 / YK-FH312
Categories
UNII
S125DW66N8
CAS number
174022-42-5
Weight
Average: 584.8262
Monoisotopic: 584.407689524
Chemical Formula
C36H56O6
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,2R,5S,8R,9R,10R,13R,14R,17S,19R)-17-[(3-carboxy-3,3-dimethylpropanoyl)oxy]-1,2,14,18,18-pentamethyl-8-(prop-1-en-2-yl)pentacyclo[11.8.0.0²,¹⁰.0⁵,⁹.0¹⁴,¹⁹]henicosane-5-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

Pharmacology

Indication

Investigated for use/treatment in HIV infection.

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.

TargetActionsOrganism
UGag-Pol polyproteinNot 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
Toxicity
Not Available
Affected organisms
  • Human Immunodeficiency Virus
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. 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. [PubMed:18043758]
  2. 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. [PubMed:16956950]
  3. 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. [PubMed:17638699]
External Links
PubChem Compound
457928
PubChem Substance
175427073
ChemSpider
403003
BindingDB
50050955
ChEBI
65484
ChEMBL
CHEMBL404519
Wikipedia
Bevirimat

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
2CompletedTreatmentHuman Immunodeficiency Virus Type 1 (HIV-1) Infection1

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
PropertyValueSource
Water Solubility0.000135 mg/mLALOGPS
logP5.88ALOGPS
logP8ChemAxon
logS-6.6ALOGPS
pKa (Strongest Acidic)4.16ChemAxon
pKa (Strongest Basic)-7.1ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area100.9 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity161.75 m3·mol-1ChemAxon
Polarizability68 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9113
Blood Brain Barrier+0.7711
Caco-2 permeable+0.5417
P-glycoprotein substrateSubstrate0.7828
P-glycoprotein inhibitor IInhibitor0.5376
P-glycoprotein inhibitor IIInhibitor0.8093
Renal organic cation transporterNon-inhibitor0.7973
CYP450 2C9 substrateNon-substrate0.8472
CYP450 2D6 substrateNon-substrate0.9272
CYP450 3A4 substrateSubstrate0.7933
CYP450 1A2 substrateNon-inhibitor0.8733
CYP450 2C9 inhibitorNon-inhibitor0.8726
CYP450 2D6 inhibitorNon-inhibitor0.9514
CYP450 2C19 inhibitorNon-inhibitor0.9112
CYP450 3A4 inhibitorNon-inhibitor0.7177
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7885
Ames testNon AMES toxic0.8579
CarcinogenicityNon-carcinogens0.9403
BiodegradationNot ready biodegradable0.9835
Rat acute toxicity3.5488 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9294
hERG inhibition (predictor II)Non-inhibitor0.8177
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

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
Triterpenoid / 18-hydroxysteroid / 18-oxosteroid / Hydroxysteroid / Oxosteroid / Steroid / Tricarboxylic acid or derivatives / Fatty acid ester / Fatty acyl / Carboxylic acid ester
Molecular Framework
Aliphatic homopolycyclic compounds
External Descriptors
dicarboxylic acid monoester, monocarboxylic acid, pentacyclic triterpenoid (CHEBI:65484)

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
  1. 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. [PubMed:18043758]

Drug created on March 19, 2008 10:37 / Updated on August 02, 2019 07:52