Silibinin

Summary

Silibinin (CHEMBL9509) is a phase-3 clinical-stage small molecule (ATC A05BA03) targeting TAS2R14; indicated across 4 conditions including hepatitis c virus infection and liver failure.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• ATC class: A05BA03
• Targets: 1 (TAS2R14)
• Indications: 4 conditions
• Clinical trials: 56
• Chemistry: 482.4 Da · C25H22O10

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL9509
Name	Silibinin
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	3086637
ATC	A05BA03
Molecular formula	C25H22O10
Molecular weight	482.4
InChIKey	SEBFKMXJBCUCAI-DBMPWETRSA-N

SMILES: COC1=C(C=CC(=C1)C2C(OC3=C(O2)C=C(C=C3)[C@@H]4[C@H](C(=O)C5=C(C=C(C=C5O4)O)O)O)CO)O

IUPAC name: (2R,3R)-3,5,7-trihydroxy-2-[3-(4-hydroxy-3-methoxyphenyl)-2-(hydroxymethyl)-2,3-dihydro-1,4-benzodioxin-6-yl]-2,3-dihydrochromen-4-one

Also known as: Legalon, Silibin, Silibinin, Silibinin a-silibinin b mixt., Silibinina, Silibinine, Silliver, Silybin, Silybine, Silymarin, silybin, silibinin

Patent coverage: 85 distinct patent families (130 SureChEMBL compound mentions), from 4 matched compound structure(s). One matched structure accounts for 113 (87%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
TAS2R14	TAS2R14	Agonist	4.25	0.1%	Q9NYV8

Broader ChEMBL bioactivity targets: 17 (assay-derived). Sample: Xanthine dehydrogenase/oxidase, Microtubule-associated protein tau, 15-hydroxyprostaglandin dehydrogenase [NAD(+)], Solute carrier organic anion transporter family member 1B1, Solute carrier organic anion transporter family member 1B3, Prothrombin, Trypsin, ATP-dependent translocase ABCB1, Lysosomal alpha-glucosidase, Polyunsaturated fatty acid lipoxygenase ALOX15.

Bioactivity

ChEMBL activities: 12 potent at pChembl ≥ 5 of 30 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
O42713	6.16	Ki	700	nM	CHEMBL_ACT_19254927
O42713	6.16	Ki	700	nM	CHEMBL_ACT_19254955
O42713	5.77	IC50	1700	nM	CHEMBL_ACT_19254938
SLCO1B3	5.49	Ki	3270	nM	CHEMBL_ACT_13798668
SLCO1B1	5.47	Ki	3370	nM	CHEMBL_ACT_13800667
PRSS1	5.43	IC50	3700	nM	CHEMBL_ACT_13442122
SLCO1B3	5.37	IC50	4266	nM	CHEMBL_ACT_13798604
CYP2C9	5.3	Ki	5000	nM	CHEMBL_ACT_6075064
SLCO1B1	5.21	IC50	6166	nM	CHEMBL_ACT_13800603
P21447	5.17	Kd	6800	nM	CHEMBL_ACT_842421
O42713	5.08	Ki	8400	nM	CHEMBL_ACT_19254882
O42713	5.07	Ki	8500	nM	CHEMBL_ACT_19254895

Target pathways

Aggregated over 1 target gene(s): TAS2R14.

Top Reactome pathways

9 total, by targets touching each:

Pathway	Targets	Genes
Signal Transduction	1	TAS2R14
Signaling by GPCR	1	TAS2R14
GPCR downstream signalling	1	TAS2R14
G alpha (i) signalling events	1	TAS2R14
Class C/3 (Metabotropic glutamate/pheromone receptors)	1	TAS2R14
GPCR ligand binding	1	TAS2R14
Sensory Perception	1	TAS2R14
Sensory perception of taste	1	TAS2R14
Sensory perception of sweet, bitter, and umami (glutamate) taste	1	TAS2R14

Dominant GO biological processes

GO term	Targets
detection of chemical stimulus involved in sensory perception of bitter taste	1
G protein-coupled receptor signaling pathway	1
signal transduction	1
sensory perception of taste	1

Indications & clinical

Indications

4 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
hepatitis C virus infection	2	MONDO:0005231	EFO:0003047
liver failure	2	MONDO:0100192	MONDO:0100192
nicotine dependence	1	MONDO:0008575	EFO:0003768

1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 56.

Phase distribution

Phase	Trials
PHASE2	15
Not specified	12
PHASE4	9
PHASE1	8
PHASE3	6
PHASE2/PHASE3	5
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02347319	PHASE4	COMPLETED	To Evaluate the Efficacy of DDB/Garlic Oil in Patients With Elevated Transaminase Chronic Liver Disease
NCT02973295	PHASE4	WITHDRAWN	Silymarin in NAFLD
NCT03130634	PHASE4	COMPLETED	The Efficacy of Silymarin as Adjuvant Therapy on Colorectal Cancer Patients Undergoing FOLFIRI Treatment
NCT03538327	PHASE4	COMPLETED	Effects of Silybin in Hypertensive Patients
NCT04490967	PHASE4	UNKNOWN	Silymarin Cream Versus Salicylic Acid in Treatment of Acne Vulgaris
NCT04816682	PHASE4	COMPLETED	Silymarin in COVID-19 Patients Admitted to Hospital With Elevated Liver Enzymes
NCT05042245	PHASE4	COMPLETED	The Efficacy and Safety of Ornithine Aspartic Acid Granules in NAFLD Against Silymarin Capsules
NCT05099601	PHASE4	UNKNOWN	Silymarin Cream Versus Combined Silymarin Cream and Microneedling in Treatment of Melasma
NCT05666765	PHASE4	UNKNOWN	Comparison Between Isotretinoin, Silymarin and Both in the Treatment of Acne Vulgaris
NCT00755950	PHASE2/PHASE3	TERMINATED	Randomized Placebo-controlled Trial Evaluating the Safety and Efficacy of Silymarin Treatment in Patients With Acute Viral Hepatitis
NCT00999349	PHASE2/PHASE3	UNKNOWN	Therapeutic Effects of Silymarin in Patients With B-thalassemia Major
NCT01049178	PHASE2/PHASE3	WITHDRAWN	Randomized Controlled Trial of Silymarin in Asthma
NCT01091324	PHASE3	UNKNOWN	Dextromethorphan and Silymarin in Chronic Kidney Disease (CKD) Patients
NCT01258686	PHASE3	COMPLETED	Clinical Study With Silymarin in the Patients With Chronic Hepatitis C Infection Who Failed Conventional Antiviral Therapy
NCT01829178	PHASE2/PHASE3	COMPLETED	Evaluation of Effects of Silymarin on Cisplatin Induced Nephrotoxicity in Upper Gastrointestinal Adenocarcinoma
NCT03216668	PHASE3	UNKNOWN	TONKA Versus Legalon for Lowering Hepatic Enzymes in Liver Function Disorder Patients.
NCT04394208	PHASE3	UNKNOWN	Silymarin in COVID-19 Pneumonia
NCT05595109	PHASE2/PHASE3	UNKNOWN	Role of Silymarin in Chemotherapy Toxicity and Cognition Improvement in Breast Cancer Patients
NCT05631041	PHASE3	UNKNOWN	Effect of Silymarin in Metastatic Colorectal Cancer Patients
NCT06114719	PHASE3	COMPLETED	Silymarin for the Prevention of Atrial Fibrillation After Cardiac Surgery
NCT06213857	PHASE2	RECRUITING	Beneficial Effect of Silymarin in Ulcerative Colitis
NCT07001150	PHASE2	RECRUITING	Role of Silymarin in Neuroprotection and Symptom Management in Parkinson’s Disease
NCT07572552	PHASE2	NOT_YET_RECRUITING	Clinical Study Evaluating the Efficacy and Safety of Fenofibrates Versus Silymarin in Adult Patients With Sepsis
NCT00055718	PHASE2	COMPLETED	Silymarin (Milk Thistle Extract) in Treating Patients With Acute Lymphoblastic Leukemia Who Are Receiving Chemotherapy
NCT00246363	PHASE1/PHASE2	COMPLETED	A Clinical Research Study Designed To Determine If Treatment of Hepatitis C With Milk Thistle is More Effective Than No Treatment In Patients Infected With Both HIV And Hepatitis C
NCT00680342	PHASE2	COMPLETED	Phase II Trial of Silymarin for Patients With Chronic Hepatitis C Who Have Failed Conventional Antiviral Treatment
NCT00680407	PHASE2	COMPLETED	Phase II Trial of Silymarin for Non-Cirrhotic Patients With Non-Alcoholic Steatohepatitis
NCT00684268	PHASE2	COMPLETED	Intravenous Silibinin in Combination With Peg-interferon and Ribavirin in Nonresponders
NCT00915200	PHASE2	COMPLETED	N-Acetylcysteine and Milk Thistle for Treatment of Diabetic Nephropathy
NCT00915681	PHASE2	TERMINATED	Intravenous Milk Thistle (Silibinin-Legalon) for Hepatic Failure Induced by Amatoxin/Amanita Mushroom Poisoning
NCT01292161	PHASE2	COMPLETED	Effects of Silybum Marianum on Treatment of Patients With Chronic Hepatitis C
NCT01518933	PHASE2	TERMINATED	Effect of LEGALON SIL on Hepatitis C Virus Recurrence in Stable Liver Transplanted Patients
NCT01535092	PHASE2	TERMINATED	Legalon SIL for the Treatment of HCV Recurrence in Liver Transplanted Patients
NCT01816490	PHASE2	COMPLETED	THISTLE - The HIV-HCV Silibinin Trial
NCT03982849	PHASE2	COMPLETED	Comparison of Topical Silymarin With Hydroquinone in the Treatment of Melasma
NCT06425705	PHASE2	COMPLETED	Impact of Silymarin Adjunct Therapy on Proteinuria in Type 2 Diabetic Patients on RAS Inhibitors
NCT07058090	PHASE1	NOT_YET_RECRUITING	Comparison of the Outcome of Treatment With Silymarin or N-Aceylcysteine in Patients Taking Anti-Tuberculous Drugs for Tuberculosis at a Tertiary Care Hospital , Karachi
NCT00065741	PHASE1	COMPLETED	Botanical/Drug Interactions in HIV: Glucuronidation
NCT00389376	PHASE1	COMPLETED	Phase I Trial of Silymarin for Chronic Liver Diseases
NCT01018615	PHASE1	COMPLETED	Safety, Metabolism, and Antioxidant Activity of Silymarin and Green Tea Extract in Patients With Chronic Hepatitis C

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

2 molecules share ≥1 primary target. Top 2 by shared-target count:

Molecule	Source	Status	Shared targets
ISOPROTERENOL	ChEMBL	Phase 4 (approved)	TAS2R14
FLUFENAMIC ACID	ChEMBL	Phase 2	TAS2R14