This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Name
Silibinin A
Accession Number
DB09298
Type
Small Molecule
Groups
Experimental, Investigational
Description

Silibinin is the major active constituent of silymarin, a standardized extract of the milk thistle seeds, containing a mixture of flavonolignans consisting of silibinin, isosilibinin, silicristin, silidianin and others. Silibinin itself is mixture of two diastereomers, silybin A and silybin B, in approximately equimolar ratio. Both in vitro and animal research suggest that silibinin has hepatoprotective (antihepatotoxic) properties that protect liver cells against toxins. Silibinin has also demonstrated in vitro anti-cancer effects against human prostate adenocarcinoma cells, estrogen-dependent and -independent human breast carcinoma cells, human ectocervical carcinoma cells, human colon cancer cells, and both small and nonsmall human lung carcinoma cells.

Structure
Thumb
Synonyms
  • silibinina
  • Silybin A
  • Silybin A (constituent of milk thistle)
  • Silymarin I
Product Ingredients
IngredientUNIICASInChI Key
Silibinin dihydrogen disuccinate disodiumNot AvailableNot AvailableNot applicable
International/Other Brands
Legalon
Categories
UNII
33X338MNE4
CAS number
22888-70-6
Weight
Average: 482.441
Monoisotopic: 482.121296908
Chemical Formula
C25H22O10
InChI Key
SEBFKMXJBCUCAI-HKTJVKLFSA-N
InChI
InChI=1S/C25H22O10/c1-32-17-6-11(2-4-14(17)28)24-20(10-26)33-16-5-3-12(7-18(16)34-24)25-23(31)22(30)21-15(29)8-13(27)9-19(21)35-25/h2-9,20,23-29,31H,10H2,1H3/t20-,23+,24-,25-/m1/s1
IUPAC Name
(2R,3R)-3,5,7-trihydroxy-2-[(2R,3R)-3-(4-hydroxy-3-methoxyphenyl)-2-(hydroxymethyl)-2,3-dihydro-1,4-benzodioxin-6-yl]-3,4-dihydro-2H-1-benzopyran-4-one
SMILES
[H][C@@]1(OC2=C(O[C@@H]1CO)C=CC(=C2)[C@@]1([H])OC2=C(C(O)=CC(O)=C2)C(=O)[C@@H]1O)C1=CC(OC)=C(O)C=C1

Pharmacology

Indication

Currently being tested as a treatment of severe intoxications with hepatotoxic substances, such as death cap (Amanita phalloides) poisoning.

Pharmacodynamics
Not Available
Mechanism of action
Not Available
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AbacavirThe metabolism of Abacavir can be decreased when combined with Silibinin A.
AcetaminophenThe metabolism of Acetaminophen can be decreased when combined with Silibinin A.
AcetazolamideThe excretion of Silibinin A can be decreased when combined with Acetazolamide.
Acetylsalicylic acidThe excretion of Silibinin A can be decreased when combined with Acetylsalicylic acid.
AcyclovirThe excretion of Silibinin A can be decreased when combined with Acyclovir.
Adefovir DipivoxilThe excretion of Silibinin A can be decreased when combined with Adefovir Dipivoxil.
AlprostadilThe excretion of Silibinin A can be decreased when combined with Alprostadil.
AlvocidibThe metabolism of Alvocidib can be decreased when combined with Silibinin A.
AmbrisentanThe excretion of Ambrisentan can be decreased when combined with Silibinin A.
Aminohippuric acidThe excretion of Silibinin A can be decreased when combined with Aminohippuric acid.
Food Interactions
Not Available

References

General References
Not Available
External Links
KEGG Drug
D08515
KEGG Compound
C07610
PubChem Compound
31553
PubChem Substance
310265190
ChemSpider
29263
BindingDB
50084982
ChEBI
9144
ChEMBL
CHEMBL431701
PharmGKB
PA166129539
Wikipedia
Silibinin

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceHepatitis C Viral Infection / Non-Alcoholic Fatty Liver Disease (NAFLD)1
1CompletedTreatmentImmune Abnormalities1
2CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection1
2CompletedTreatmentNon-Alcoholic Fatty Liver Disease (NAFLD)1
2CompletedTreatmentNon-Alcoholic Steatohepatitis1
2, 3Unknown StatusTreatmentAcute iron intoxication / Beta-Thalassemia Major1
2, 3WithdrawnTreatmentAsthma, Allergic1
3RecruitingTreatmentLiver Function Failure1
4CompletedTreatmentChronic Liver Diseases (CLD)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
PropertyValueSource
Water Solubility0.0926 mg/mLALOGPS
logP2.35ALOGPS
logP2.63ChemAxon
logS-3.7ALOGPS
pKa (Strongest Acidic)7.75ChemAxon
pKa (Strongest Basic)-3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count10ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area155.14 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity120.29 m3·mol-1ChemAxon
Polarizability48.41 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

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
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , negativeLC-MS/MSsplash10-0ue9-0943800000-af015f0adf79e0968a5a
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0gvk-2952100000-c3d2a818a44f51b39801
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0f7k-0931200000-a04a951f896c0248d2fe

Taxonomy

Description
This compound belongs to the class of organic compounds known as flavonolignans. These are non-conventional lignans that derived from flavonoids. They are characterized by a p-dioxin ring substituted at one carbon atom by a C3C6 (phenylpropan) group and fused to the B-ring of the 2-phenylchromene moiety.
Kingdom
Organic compounds
Super Class
Lignans, neolignans and related compounds
Class
Flavonolignans
Sub Class
Not Available
Direct Parent
Flavonolignans
Alternative Parents
3-hydroxyflavonoids / 5-hydroxyflavonoids / 7-hydroxyflavonoids / Flavanonols / Phenylbenzo-1,4-dioxanes / Chromones / Methoxyphenols / Benzo-1,4-dioxanes / Phenoxy compounds / Anisoles
show 13 more
Substituents
Flavonolignan / Hydroxyflavonoid / 3-hydroxyflavonoid / Flavanonol / Flavanone / 7-hydroxyflavonoid / 5-hydroxyflavonoid / Flavan / Phenylbenzodioxane / 2-phenylbenzo-1,4-dioxane
show 34 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
aromatic ether, polyphenol, benzodioxine, flavonolignan (CHEBI:9144)

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inhibitor
General Function
Steroid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A1
Uniprot ID
P22309
Uniprot Name
UDP-glucuronosyltransferase 1-1
Molecular Weight
59590.91 Da
References
  1. Williams JA, Hyland R, Jones BC, Smith DA, Hurst S, Goosen TC, Peterkin V, Koup JR, Ball SE: Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos. 2004 Nov;32(11):1201-8. doi: 10.1124/dmd.104.000794. Epub 2004 Aug 10. [PubMed:15304429]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Curator comments
This is based on the findings of in vitro studies using human OAT1 expressed on MDCK cells.
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one ...
Gene Name
SLC22A6
Uniprot ID
Q4U2R8
Uniprot Name
Solute carrier family 22 member 6
Molecular Weight
61815.78 Da
References
  1. VanWert AL, Gionfriddo MR, Sweet DH: Organic anion transporters: discovery, pharmacology, regulation and roles in pathophysiology. Biopharm Drug Dispos. 2010 Jan;31(1):1-71. doi: 10.1002/bdd.693. [PubMed:19953504]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P: Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. J Med Chem. 2012 May 24;55(10):4740-63. doi: 10.1021/jm300212s. Epub 2012 May 15. [PubMed:22541068]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
Gene Name
SLCO1B3
Uniprot ID
Q9NPD5
Uniprot Name
Solute carrier organic anion transporter family member 1B3
Molecular Weight
77402.175 Da
References
  1. Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P: Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. J Med Chem. 2012 May 24;55(10):4740-63. doi: 10.1021/jm300212s. Epub 2012 May 15. [PubMed:22541068]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent transport of organic anions such as taurocholate, the prostaglandins PGD2, PGE1, PGE2, leukotriene C4, thromboxane B2 and iloprost.
Gene Name
SLCO2B1
Uniprot ID
O94956
Uniprot Name
Solute carrier organic anion transporter family member 2B1
Molecular Weight
76709.98 Da
References
  1. Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P: Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. J Med Chem. 2012 May 24;55(10):4740-63. doi: 10.1021/jm300212s. Epub 2012 May 15. [PubMed:22541068]

Drug created on October 30, 2015 14:42 / Updated on November 02, 2018 08:49