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Identification
NameProbucol
Accession NumberDB01599
TypeSmall Molecule
GroupsApproved
DescriptionA drug used to lower LDL and HDL cholesterol yet has little effect on serum-triglyceride or VLDL cholesterol. (From Martindale, The Extra Pharmacopoeia, 30th ed, p993).
Structure
Thumb
Synonyms
4,4'- (Isopropylidenedithio)bis(2,6-di-tert-butylphenol)
Acetone bis(3,5-di-tert-butyl-4-hydroxyphenyl) mercaptole
Biphenabid
Bisbid
Bisphenabid
DH-581
Lesterol
Lorelco
Lurselle
Probucolum
Serterol
Superlipid
External Identifiers
  • DH-581
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
LorelcoTablet250 mgOralSanofi Aventis Canada Inc1995-12-312009-04-03Canada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
SinlestalNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIP3CTH044XJ
CAS number23288-49-5
WeightAverage: 516.842
Monoisotopic: 516.30957216
Chemical FormulaC31H48O2S2
InChI KeyFYPMFJGVHOHGLL-UHFFFAOYSA-N
InChI
InChI=1S/C31H48O2S2/c1-27(2,3)21-15-19(16-22(25(21)32)28(4,5)6)34-31(13,14)35-20-17-23(29(7,8)9)26(33)24(18-20)30(10,11)12/h15-18,32-33H,1-14H3
IUPAC Name
2,6-di-tert-butyl-4-({2-[(3,5-di-tert-butyl-4-hydroxyphenyl)sulfanyl]propan-2-yl}sulfanyl)phenol
SMILES
CC(C)(SC1=CC(=C(O)C(=C1)C(C)(C)C)C(C)(C)C)SC1=CC(=C(O)C(=C1)C(C)(C)C)C(C)(C)C
Pharmacology
IndicationUsed to lower LDL and HDL cholesterol.
Structured Indications Not Available
PharmacodynamicsProbucol lowers the level of cholesterol in the bloodstream by increasing the rate of LDL catabolism. Additionally, probucol may inhibit cholesterol synthesis and delay cholesterol absorption. Probucol is a powerful antioxidant drug normally used to prevent vascular disease caused by the free radicals in the body.
Mechanism of actionProbucol lowers serum cholesterol by increasing the fractional rate of low-density lipoprotein (LDL) catabolism in the final metabolic pathway for cholesterol elimination from the body. Additionally, probucol may inhibit early stages of cholesterol biosynthesis and slightly inhibit dietary cholesterol absorption. Recent information suggests that probucol may inhibit the oxidation and tissue deposition of LDL cholesterol, thereby inhibiting atherogenesis. It appears to inhibits ABCA1-mediated cellular lipid efflux.
TargetKindPharmacological actionActionsOrganismUniProt ID
ATP-binding cassette sub-family A member 1Proteinyes
inhibitor
HumanO95477 details
Liver carboxylesterase 1ProteinunknownNot AvailableHumanP23141 details
Related Articles
AbsorptionAbsorption from the gastrointestinal tract is limited and variable (about 7%).
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeRanges from 12 hours to more than 500 hours, the longest half-life probably being in adipose tissue.
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available
References
Synthesis Reference

Claudio Giordano, Giuseppe Barreca, “Process for preparing an intermediate useful in the syntheis of probucol.” U.S. Patent US5157156, issued July, 1988.

US5157156
General ReferencesNot Available
External Links
ATC CodesC10AX02
AHFS Codes
  • 24:06.92
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.992
Blood Brain Barrier+0.8118
Caco-2 permeable+0.778
P-glycoprotein substrateNon-substrate0.6117
P-glycoprotein inhibitor INon-inhibitor0.8088
P-glycoprotein inhibitor IINon-inhibitor0.8381
Renal organic cation transporterNon-inhibitor0.868
CYP450 2C9 substrateNon-substrate0.6651
CYP450 2D6 substrateNon-substrate0.6765
CYP450 3A4 substrateSubstrate0.5288
CYP450 1A2 substrateNon-inhibitor0.8029
CYP450 2C9 inhibitorNon-inhibitor0.8098
CYP450 2D6 inhibitorNon-inhibitor0.9232
CYP450 2C19 inhibitorNon-inhibitor0.7852
CYP450 3A4 inhibitorNon-inhibitor0.7851
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8793
Ames testNon AMES toxic0.9398
CarcinogenicityNon-carcinogens0.6603
BiodegradationNot ready biodegradable1.0
Rat acute toxicity1.9829 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9868
hERG inhibition (predictor II)Non-inhibitor0.7771
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
TabletOral250 mg
Prices
Unit descriptionCostUnit
Probucol powder2.45USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point125 °CPhysProp
Predicted Properties
PropertyValueSource
Water Solubility4.18e-05 mg/mLALOGPS
logP8.92ALOGPS
logP10.57ChemAxon
logS-7.1ALOGPS
pKa (Strongest Acidic)10.29ChemAxon
pKa (Strongest Basic)-5.1ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area40.46 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity159.26 m3·mol-1ChemAxon
Polarizability62.35 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as phenylpropanes. These are organic compounds containing a phenylpropane moiety.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassPhenylpropanes
Direct ParentPhenylpropanes
Alternative Parents
Substituents
  • Phenylpropane
  • Thiophenol ether
  • Alkylarylthioether
  • Phenol
  • Dithioketal
  • Thioacetal
  • Sulfenyl compound
  • Thioether
  • Hydrocarbon derivative
  • Organosulfur compound
  • Organooxygen compound
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Syntaxin binding
Specific Function:
cAMP-dependent and sulfonylurea-sensitive anion transporter. Key gatekeeper influencing intracellular cholesterol transport.
Gene Name:
ABCA1
Uniprot ID:
O95477
Molecular Weight:
254299.89 Da
References
  1. Favari E, Zanotti I, Zimetti F, Ronda N, Bernini F, Rothblat GH: Probucol inhibits ABCA1-mediated cellular lipid efflux. Arterioscler Thromb Vasc Biol. 2004 Dec;24(12):2345-50. Epub 2004 Oct 28. [PubMed:15514211 ]
  2. Yamamoto A: A uniqe antilipidemic drug--probucol. J Atheroscler Thromb. 2008 Dec;15(6):304-5. Epub 2008 Dec 11. [PubMed:19075491 ]
  3. de la Llera-Moya M, Drazul-Schrader D, Asztalos BF, Cuchel M, Rader DJ, Rothblat GH: The ability to promote efflux via ABCA1 determines the capacity of serum specimens with similar high-density lipoprotein cholesterol to remove cholesterol from macrophages. Arterioscler Thromb Vasc Biol. 2010 Apr;30(4):796-801. doi: 10.1161/ATVBAHA.109.199158. Epub 2010 Jan 14. [PubMed:20075420 ]
  4. Sirtori CR, Manzoni C, Lovati MR: Mechanisms of lipid-lowering agents. Cardiology. 1991;78(3):226-35. [PubMed:1868500 ]
  5. Shichiri M, Takanezawa Y, Rotzoll DE, Yoshida Y, Kokubu T, Ueda K, Tamai H, Arai H: ATP-binding cassette transporter A1 is involved in hepatic alpha-tocopherol secretion. J Nutr Biochem. 2010 May;21(5):451-6. doi: 10.1016/j.jnutbio.2009.02.002. Epub 2009 May 7. [PubMed:19427182 ]
  6. Arakawa R, Tsujita M, Iwamoto N, Ito-Ohsumi C, Lu R, Wu CA, Shimizu K, Aotsuka T, Kanazawa H, Abe-Dohmae S, Yokoyama S: Pharmacological inhibition of ABCA1 degradation increases HDL biogenesis and exhibits antiatherogenesis. J Lipid Res. 2009 Nov;50(11):2299-305. doi: 10.1194/jlr.M900122-JLR200. Epub 2009 May 20. [PubMed:19458386 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Triglyceride lipase activity
Specific Function:
Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acyl-CoA ester. Hydrolyzes the methyl ester group of cocaine to form benzoylecgonine. Catalyzes the transesterification of cocaine to form cocaethylene. Displays fatty acid ethyl ester synthase activity,...
Gene Name:
CES1
Uniprot ID:
P23141
Molecular Weight:
62520.62 Da
References
  1. Jeon SM, Park YB, Kwon OS, Huh TL, Lee WH, Do KM, Park T, Choi MS: Vitamin E supplementation alters HDL-cholesterol concentration and paraoxonase activity in rabbits fed high-cholesterol diet: comparison with probucol. J Biochem Mol Toxicol. 2005;19(5):336-46. [PubMed:16292755 ]
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Drug created on August 29, 2007 12:43 / Updated on August 17, 2016 12:23