Probucol

Identification

Generic Name
Probucol
DrugBank Accession Number
DB01599
Background

A 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).

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 516.842
Monoisotopic: 516.30957216
Chemical Formula
C31H48O2S2
Synonyms
  • 4,4'- (Isopropylidenedithio)bis(2,6-di-tert-butylphenol)
  • Acetone bis(3,5-di-tert-butyl-4-hydroxyphenyl) mercaptole
  • Biphenabid
  • Bisbid
  • Bisphenabid
  • Probucol
  • Probucolum
External IDs
  • DH-581

Pharmacology

Indication

Used to lower LDL and HDL cholesterol.

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Contraindications & Blackbox Warnings
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Pharmacodynamics

Probucol lowers cholesterol levels by increasing LDL (low-density lipoprotein) breakdown. 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 action

Probucol 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. This drug may also act to inhibit the initial stages of cholesterol synthesis and act to inhibit the absorption of cholesterol from the diet. 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.

TargetActionsOrganism
AATP-binding cassette sub-family A member 1
inhibitor
Humans
ULiver carboxylesterase 1Not AvailableHumans
Absorption

Absorption from the gastrointestinal tract is limited and variable (about 7%).

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

Ranges from 12 hours to more than 500 hours, the longest half-life probably being in adipose tissue.

Clearance

Not Available

Adverse Effects
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Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
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.
DrugInteraction
AcrivastineThe risk or severity of QTc prolongation can be increased when Acrivastine is combined with Probucol.
AdenosineThe risk or severity of QTc prolongation can be increased when Adenosine is combined with Probucol.
AjmalineThe risk or severity of QTc prolongation can be increased when Ajmaline is combined with Probucol.
AlfuzosinThe risk or severity of QTc prolongation can be increased when Alfuzosin is combined with Probucol.
AlimemazineThe risk or severity of QTc prolongation can be increased when Alimemazine is combined with Probucol.
Food Interactions
  • Take with food. Food increases bioavailability.

Products

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International/Other Brands
Lesterol / Lurselle / Serterol / Sinlestal / Superlipid
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
LorelcoTablet250 mgOralSanofi Aventis1995-12-312009-04-03Canada flag

Categories

ATC Codes
C10AX02 — Probucol
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as phenylpropanes. These are organic compounds containing a phenylpropane moiety.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Phenylpropanes
Direct Parent
Phenylpropanes
Alternative Parents
Thiophenol ethers / Phenols / Dithioketals / Alkylarylthioethers / Sulfenyl compounds / Organooxygen compounds / Hydrocarbon derivatives
Substituents
Alkylarylthioether / Aromatic homomonocyclic compound / Aryl thioether / Dithioketal / Hydrocarbon derivative / Organic oxygen compound / Organooxygen compound / Organosulfur compound / Phenol / Phenylpropane
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
polyphenol, dithioketal (CHEBI:8427)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
P3CTH044XJ
CAS number
23288-49-5
InChI Key
FYPMFJGVHOHGLL-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

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 References
Not Available
Human Metabolome Database
HMDB0015537
KEGG Drug
D00476
KEGG Compound
C07373
PubChem Compound
4912
PubChem Substance
46508876
ChemSpider
4743
BindingDB
50007260
RxNav
8699
ChEBI
8427
ChEMBL
CHEMBL608
ZINC
ZINC000001530755
Therapeutic Targets Database
DAP000916
PharmGKB
PA451107
Drugs.com
Drugs.com Drug Page
Wikipedia
Probucol

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedHealth Services ResearchHealthy Volunteers (HV)1
4CompletedTreatmentArteriosclerosis Obliterans / Type 2 Diabetes Mellitus1
4CompletedTreatmentAtherosclerosis Cerebral Infarction1
4CompletedTreatmentChronic Nephropathy1
4CompletedTreatmentDiabetic Nephropathy1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Gallipot
  • Letco Medical Inc.
Dosage Forms
FormRouteStrength
TabletOral250 mg
TabletOral
Prices
Unit descriptionCostUnit
Probucol powder2.45USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)125 °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 FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-0uki-0090250000-bea4462f54c2e521b686
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-000i-0020930000-22afb2f694f8bb03eb1a
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-000i-0000910000-4679aad4c3360aa9993a
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-052r-0010910000-520f5105e6ccc4b76f67
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-00kr-2001940000-42635e176164c9513649
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-066s-0540910000-d1c9b7b06d5fad8190fb
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-00di-0002900000-5ed3989e96e8a943baf7
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-256.488568
predicted
DarkChem Lite v0.1.0
[M-H]-257.835168
predicted
DarkChem Lite v0.1.0
[M-H]-230.1628
predicted
DeepCCS 1.0 (2019)
[M+H]+256.873368
predicted
DarkChem Lite v0.1.0
[M+H]+258.547868
predicted
DarkChem Lite v0.1.0
[M+H]+232.55836
predicted
DeepCCS 1.0 (2019)
[M+Na]+256.472468
predicted
DarkChem Lite v0.1.0
[M+Na]+257.122168
predicted
DarkChem Lite v0.1.0
[M+Na]+238.47133
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein
Organism
Humans
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
Uniprot Name
ATP-binding cassette sub-family A member 1
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. [Article]
  2. Yamamoto A: A uniqe antilipidemic drug--probucol. J Atheroscler Thromb. 2008 Dec;15(6):304-5. Epub 2008 Dec 11. [Article]
  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. [Article]
  4. Sirtori CR, Manzoni C, Lovati MR: Mechanisms of lipid-lowering agents. Cardiology. 1991;78(3):226-35. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
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 acy...
Gene Name
CES1
Uniprot ID
P23141
Uniprot Name
Liver carboxylesterase 1
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. [Article]

Drug created at August 29, 2007 18:43 / Updated at February 21, 2021 18:51