SILIBININ A

Possibly Marketed Outside US

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C25H22O10
Molecular Weight	482.4362
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=C(O)C=CC(=C1)[C@H]2OC3=C(O[C@@H]2CO)C=CC(=C3)[C@H]4OC5=CC(O)=CC(O)=C5C(=O)[C@@H]4O

InChI

InChIKey=SEBFKMXJBCUCAI-HKTJVKLFSA-N

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

HIDE SMILES / InChI

Molecular Formula	C25H22O10
Molecular Weight	482.4362
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	4 / 4
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.squarepharma.com.bd/downloads/Silybin%20DS.PDF
Curator's Comment: description was created based on several sources, including: https://www.ncbi.nlm.nih.gov/pubmed/17305535 | http://www.webmd.com/heart-disease/milk-thistle-benefits-and-side-effects#1

Silymarin, a plant-derived flavonoid from the plant Silybum marianum, is considered the most potential drug to treat almost all kind of liver diseases, particularly alcoholic liver disease, acute and chronic viral hepatitis and toxins-mediated liver dysfunctions. The main component of the silymarin complex is silybin, synonymous with silibinin, sometimes incorrectly called silybinin, which is a mixture of two diastereomers A and B in approximately 1:1 proportion. The drug possess hepatoprotective and antioxidant activity. The hepatoprotective effect is due to stimulation of synthesis of structural and functional proteins and phospholipids, as well as acceleration of the regeneration of hepatocytes. Antioxidant effect is determined by interaction of bioflavones with free radicals in the liver and its detoxication. In such manner the process of peroxidation of the lipids is interrupted and further liver destruction is prevented. Side effect is a mild laxative effect has occasionally been observed.

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
response to oxidative stress 20 Target ID: GO:0006979 Sources: https://www.squarepharma.com.bd/downloads/Silybin%20DS.PDF	Modulator 846
Estrogen receptor beta 113 Target ID: CHEMBL3021 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14568570	Agonist 2752
P-glycoprotein 1 54 Target ID: CHEMBL4302 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17305535 \| https://www.ncbi.nlm.nih.gov/pubmed/15072439	Inhibitor 8504

Conditions

Condition	Modality	Highest Phase	Product
Liver cirrhosis 15 Sources: https://www.squarepharma.com.bd/downloads/Silybin%20DS.PDF https://www.ncbi.nlm.nih.gov/pubmed/28125040	Primary	Approved 8583	Milk Thistle Approved Use It is indicated for the treatment of jaundice, chronic inflammatory liver conditions, i.e. hepatitis, alcoholic liver damage and hepatic cirrhosis. Launch Date 2000
Hepatitis 8 Sources: https://www.squarepharma.com.bd/downloads/Silybin%20DS.PDF	Primary	Approved 8583	Milk Thistle Approved Use It is indicated for the treatment of jaundice, chronic inflammatory liver conditions, i.e. hepatitis, alcoholic liver damage and hepatic cirrhosis. Launch Date 2000
Gallbladder disease 13 Sources: http://www.naturesgardenonline.com/ns/DisplayMonograph.asp?storeID=4qv7af8nchqt8hx4xqu61nerl9mtecuf&DocID=bottomline-milkthistle	Primary	Approved 8583	Milk Thistle Approved Use It is indicated for the treatment of jaundice, chronic inflammatory liver conditions, i.e. hepatitis, alcoholic liver damage and hepatic cirrhosis. Launch Date 2000

C_max

Value	Dose	Co-administered	Analyte	Population
15.69 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29273470/	48.7 mg single, oral dose: 48.7 mg route of administration: Oral experiment type: SINGLE co-administered:		SILIBININ A plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
37.17 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29273470/	48.7 mg single, oral dose: 48.7 mg route of administration: Oral experiment type: SINGLE co-administered:		SILIBININ A plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.98 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29273470/	48.7 mg single, oral dose: 48.7 mg route of administration: Oral experiment type: SINGLE co-administered:		SILIBININ A plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946 inducer 1087 inhibitor 2252	inhibitor 2438 substrate 1193	inhibitor 2507 substrate 1388	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
UGT 45 OATP2B1 157 OATP1B3 961 OATP1B1 1079 CYP2E1 1060 CYP1A2 2153 CYP19A1 429 CYP2C19 2057 CYP2A6 879 BSEP 550 MRP2 499	CYP2B6 776 UGT2B10 131 CYP2C8 810 CYP2E1 729 UGT1A8 323 UGT1A3 470 UGT2B17 237 UGT1A9 423 CYP1A2 1197 CYP2A6 626 P-gp 2052 CYP2C19 1119 UGT1A7 249 UGT1A10 331 UGT2B15 236 UGT1A1 479 UGT2B4 278 UGT1A6 343 UGT2B7 456 UGT1A4 399 MRP2 252 BCRP 697	CYP1A2 832

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP19A1 430	inhibitor 4027 Sources: https://frdb.rbsapp.net/loadTabs/2935/yoshipt63@gmail.com Page: 25.0	inconclusive [IC50 26.6032 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://frdb.rbsapp.net/loadTabs/2935/yoshipt63@gmail.com Page: 31.0	inconclusive [IC50 34.6713 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/10895987/	no [IC50 309 uM]
CYP2A6 911	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/10895987/	no [IC50 541 uM]
CYP2E1 1146	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/10895987/	no [IC50 799 uM]
BSEP 554	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/23695864/	no
CYP1A2 2333	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/15977188/	no
CYP1A2 2333	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/10895987/	no
CYP3A4 2633	inducer 1966 Sources: https://frdb.rbsapp.net/loadTabs/2935/yoshipt63@gmail.com Page: 358.0	no
UGT 70	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/23673225/	weak
OATP1B3 970	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNzQzMTIxIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDQzMTcwMSJ9fQ==	yes [IC50 2.7 uM]
OATP2B1 162	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNzQzMTI0IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDQzMTcwMSJ9fQ==	yes [IC50 4.5 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://frdb.rbsapp.net/loadTabs/2935/yoshipt63@gmail.com Page: 7.0	yes [IC50 5.6243 uM]
MRP2 625	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/23695864/	yes [IC50 6.79 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://frdb.rbsapp.net/loadTabs/2935/yoshipt63@gmail.com \| https://pubmed.ncbi.nlm.nih.gov/35061161/ Page: 9.0	yes [IC50 8.709 uM]	yes (pharmacogenomic study) Comment: Increase in AUC and Cmax by 0.873 and 0.294 folds, respectively in CYP2C91/3 after co-administration of silybin A exhibited a minor interaction with losartan. Sources: https://frdb.rbsapp.net/loadTabs/2935/yoshipt63@gmail.com \| https://pubmed.ncbi.nlm.nih.gov/35061161/ Page: 9.0
OATP1B1 1095	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNjk3NjY4IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDQzMTcwMSJ9fQ==	yes [IC50 9.7 uM]

Drug as victim

Target	Modality	Activity
UGT1A1 479	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/31727359/	major
UGT1A3 470	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/31727359/	minor
UGT1A7 249	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/31727359/	minor
UGT1A8 323	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/31727359/	minor
UGT1A9 423	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/31727359/	minor
CYP1A2 1197	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/29414024/	no
CYP2A6 626	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/29414024/	no
CYP2B6 776	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/29414024/	no
CYP2C19 1119	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/29414024/	no
CYP2C9 1193	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/29414024/	no
CYP2D6 1388	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/29414024/	no
CYP2E1 729	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/29414024/	no
P-gp 2052	substrate 4014 Sources: https://frdb.rbsapp.net/loadTabs/2935/yoshipt63@gmail.com Page: 357 \| 358	no
UGT1A4 399	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/31727359/	no
UGT2B10 131	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/31727359/	no
UGT2B15 236	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/31727359/	no
UGT2B17 237	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/31727359/	no
UGT2B4 278	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/31727359/	no
UGT1A10 331	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/31727359/	weak
UGT1A6 343	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/31727359/	weak
UGT2B7 456	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/31727359/	weak
BCRP 697	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/23695864/	yes
CYP2C8 810	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/29414024/	yes
CYP3A4 1946	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/29414024/	yes
MRP2 252	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/23695864/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://frdb.rbsapp.net/loadTabs/2935/yoshipt63@gmail.com Page: 373.0

PubMed

Title	Date	PubMed
Blockade of lipid accumulation by silibinin in adipocytes and zebrafish.	2015-02-05	25559859
The binding of silibinin to ERp57.	2014-04-25	24530445
Silibinin induces apoptosis of HT29 colon carcinoma cells through early growth response-1 (EGR-1)-mediated non-steroidal anti-inflammatory drug-activated gene-1 (NAG-1) up-regulation.	2014-03-25	24440808
Silibinin potentially attenuates arsenic-induced oxidative stress mediated cardiotoxicity and dyslipidemia in rats.	2014-03	24062023
Silibinin as a potential therapeutic for sulfur mustard injuries.	2013-12-05	23810508
Silibinin inhibits hepatitis C virus entry into hepatocytes by hindering clathrin-dependent trafficking.	2013-11	23701235
Silibinin ameliorates arsenic induced nephrotoxicity by abrogation of oxidative stress, inflammation and apoptosis in rats.	2012-12	23070905
Protective effect of curcumin, silymarin and N-acetylcysteine on antitubercular drug-induced hepatotoxicity assessed in an in vitro model.	2012-08	22318308
In vitro determination of anticryptosporidial activity of phytogenic extracts and compounds.	2012-07	22278729
Antiplasmodial activity of flavonol quercetin and its analogues in Plasmodium falciparum: evidence from clinical isolates in Bangladesh and standardized parasite clones.	2012-06	22215188
Silibinin potentially protects arsenic-induced oxidative hepatic dysfunction in rats.	2012-05	22229868
Synergistic effects of arsenic trioxide and silibinin on apoptosis and invasion in human glioblastoma U87MG cell line.	2012-02	21969006
Metabolic effects of silibinin in the rat liver.	2012-01-25	22137898
Differential in vitro effects of intravenous versus oral formulations of silibinin on the HCV life cycle and inflammation.	2011-01-28	21297992
Multiple effects of silymarin on the hepatitis C virus lifecycle.	2010-06	20512985
Identification of hepatoprotective flavonolignans from silymarin.	2010-03-30	20231449
Silibinin and related compounds are direct inhibitors of hepatitis C virus RNA-dependent RNA polymerase.	2010-03	19962982
Capsaicin sensitizes malignant glioma cells to TRAIL-mediated apoptosis via DR5 upregulation and survivin downregulation.	2010-03	19939880
The protective effect of silibinin against mitomycin C-induced intrinsic apoptosis in human melanoma A375-S2 cells.	2009-10	19834285
AKR1C3 as a potential target for the inhibitory effect of dietary flavonoids.	2009-03-16	19007764
Inhibition effect of flavonoids on monocarboxylate transporter 1 (MCT1) in Caco-2 cells.	2007-11	17976262
Hepatoprotective efficacy of certain flavonoids against microcystin induced toxicity in mice.	2007-10	17696131
Increased expression of the MGMT repair protein mediated by cysteine prodrugs and chemopreventative natural products in human lymphocytes and tumor cell lines.	2007-02	16950796
Silibinin activates p53-caspase 2 pathway and causes caspase-mediated cleavage of Cip1/p21 in apoptosis induction in bladder transitional-cell papilloma RT4 cells: evidence for a regulatory loop between p53 and caspase 2.	2006-11	16777994
Effect of silibinin on the growth and progression of primary lung tumors in mice.	2006-06-21	16788158
Antiparasitic activity of flavonoids and isoflavones against Cryptosporidium parvum and Encephalitozoon intestinalis.	2006-06	16684116
MDR- and CYP3A4-mediated drug-herbal interactions.	2006-03-27	16442130
Effects of silymarin flavonolignans and synthetic silybin derivatives on estrogen and aryl hydrocarbon receptor activation.	2005-11-05	16076518
Hepatoprotective and antifibrotic effect of a new silybin-phosphatidylcholine-Vitamin E complex in rats.	2005-11	16169303
Inhibition of rat liver UDP-glucuronosyltransferase by silymarin and the metabolite silibinin-glucuronide.	2005-06-24	15921999
Silibinin prevents cholestasis-associated retrieval of the bile salt export pump, Bsep, in isolated rat hepatocyte couplets: possible involvement of cAMP.	2005-04-01	15763547
Silybin inactivates cytochromes P450 3A4 and 2C9 and inhibits major hepatic glucuronosyltransferases.	2004-06	15155549
Stimulatory effects of silibinin and silicristin from the milk thistle Silybum marianum on kidney cells.	1999-09	10454517
Inhibition of reverse transcriptases by flavonoids.	1989-09	2480745

Patents

Sample Use Guides

In Vivo Use Guide

70 mg or 140 mg capsule should be taken 3 times daily. The medication should be continued until the relief of the symptoms according to the advice of a physician.

Route of Administration: Oral

In Vitro Use Guide

Silybin at pharmacologically achievable in vivo concentrations (0.02–20 uM) increased insulin-like growth factorbinding protein 3 (IGFBP-3) accumulation in androgenindependent prostate cancer PC-3 cells in conditioned medium and caused a dose-dependent increase of IGFBP-3 mRNA abundance with a 9-fold increase over baseline at 20 uM concentration.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 19:30:28 GMT 2025` Edited by `admin` on `Mon Mar 31 19:30:28 GMT 2025`
Record UNII	33X338MNE4
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

SILIBININ A

Common Name

English

NSC-651520

Preferred Name

English

SILYBIN A (CONSTITUENT OF MILK THISTLE) [DSC]

Common Name

English

SILYBIN A [MI]

Common Name

English

4H-1-BENZOPYRAN-4-ONE, 2-((2R,3R)-2,3-DIHYDRO-3-(4-HYDROXY-3-METHOXYPHENYL)-2-(HYDROXYMETHYL)-1,4-BENZODIOXIN-6-YL)-2,3-DIHYDRO-3,5,7-TRIHYDROXY-, (2R,3R)-

Systematic Name

English

SILYBIN A

Common Name

English

SILYMARIN I

Common Name

English

Code System Code Type Description

FDA UNII

33X338MNE4