Berberine

Summary

Berberine (CHEMBL295124) is an approved small-molecule antilipemic drug targeting CYP1B1 and CYP2D6; indicated across 6 conditions including type 2 diabetes mellitus and metabolic dysfunction-associated steatotic liver disease.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• Targets: 2 (CYP1B1, CYP2D6)
• Indications: 6 conditions
• Clinical trials: 61
• Chemistry: 336.4 Da · C20H18NO4+

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL295124
Name	Berberine
Type	Small molecule
Max phase	4
FDA approved	no
PubChem CID	2353
ChEBI	CHEBI:16118
Molecular formula	C20H18NO4+
Molecular weight	336.4
InChIKey	YBHILYKTIRIUTE-UHFFFAOYSA-N

SMILES: COC1=C(C2=C[N+]3=C(C=C2C=C1)C4=CC5=C(C=C4CC3)OCO5)OC

IUPAC name: 16,17-dimethoxy-5,7-dioxa-13-azoniapentacyclo[11.8.0.02,10.04,8.015,20]henicosa-1(13),2,4(8),9,14,16,18,20-octaene

Pharmacological roles (ChEBI): antilipemic drug, hypoglycemic agent, antioxidant, potassium channel blocker, antineoplastic agent, EC 1.1.1.21 (aldehyde reductase) inhibitor, EC 1.1.1.141 [15-hydroxyprostaglandin dehydrogenase (NAD+)] inhibitor, EC 1.13.11.52 (indoleamine 2,3-dioxygenase) inhibitor, EC 1.21.3.3 (reticuline oxidase) inhibitor, EC 2.1.1.116 [3’-hydroxy-N-methyl-(S)-coclaurine 4’-O-methyltransferase] inhibitor, EC 3.1.1.4 (phospholipase A2) inhibitor, EC 3.4.21.26 (prolyl oligopeptidase) inhibitor, EC 3.4.14.5 (dipeptidyl-peptidase IV) inhibitor, EC 3.1.3.48 (protein-tyrosine-phosphatase) inhibitor, EC 3.1.1.7 (acetylcholinesterase) inhibitor, EC 3.1.1.8 (cholinesterase) inhibitor, EC 2.7.11.10 (IκB kinase) inhibitor, EC 2.1.1.122 [(S)-tetrahydroprotoberberine N-methyltransferase] inhibitor, geroprotector.

Also known as: Berbericine, Berberin, Berberine, Berberone, Majarine, Thalsine, Umbellatin, Umbellatine, SID11112431, SID26753128, SID104171310, berberine

Parent form; salt/anhydrous children: CHEMBL12089, CHEMBL492613, CHEMBL1985435

Patent coverage: 12,280 distinct patent families (26,682 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 26,259 (98%) 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
CYP1B1	CYP1B1	Inhibition	7.36	0.1%	Q16678
CYP2D6	CYP2D6	Inhibition	5.4	0.5%	P10635

Broader ChEMBL bioactivity targets: 32 (assay-derived). Sample: Microtubule-associated protein tau, Survival motor neuron protein, Fructose-bisphosphate aldolase, Inositol monophosphatase 1, Cholinesterase, Thyrotropin receptor, Neuraminidase, Menin/Histone-lysine N-methyltransferase MLL, 5’-AMP-activated protein kinase catalytic subunit alpha-2, Tryptophan 2,3-dioxygenase.

Bioactivity

ChEMBL activities: 31 potent at pChembl ≥ 5 of 52 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
TDO2	7.52	IC50	30	nM	CHEMBL_ACT_26130523
CYP1B1	7.36	Ki	44	nM	CHEMBL_ACT_18157596
CYP1B1	7.03	IC50	94	nM	CHEMBL_ACT_18948707
ACHE	7	IC50	100	nM	CHEMBL_ACT_15628432
IDO1	6.58	IC50	260	nM	CHEMBL_ACT_26130521
CYP1B1	6.48	IC50	330	nM	CHEMBL_ACT_18157597
O42275	6.43	IC50	374	nM	CHEMBL_ACT_10866598
O42275	6.43	IC50	374	nM	CHEMBL_ACT_7936981
PPARA	6.24	EC50	580	nM	CHEMBL_ACT_25031295
ACHE	6.16	IC50	700	nM	CHEMBL_ACT_18960688
PPARA	6.14	Ki	730	nM	CHEMBL_ACT_25031308
BCHE	5.96	IC50	1090	nM	CHEMBL_ACT_15628449
ACHE	5.88	IC50	1330	nM	CHEMBL_ACT_25030819
O42275	5.8	IC50	1600	nM	CHEMBL_ACT_18255048
CYP1B1	5.6	IC50	2500	nM	CHEMBL_ACT_18948701
HIF1A	5.6	Potency	2512	nM	CHEMBL_ACT_4129754
HIF1A	5.6	Potency	2512	nM	CHEMBL_ACT_4518790
CYP2D6	5.6	Potency	2512	nM	CHEMBL_ACT_4965796
CYP2D6	5.6	AC50	2512	nM	CHEMBL_ACT_5987156
A8B2U2	5.5	Potency	3155	nM	CHEMBL_ACT_4587097
AKR1C3	5.39	IC50	4080	nM	CHEMBL_ACT_22396339
P97697	5.3	Potency	5012	nM	CHEMBL_ACT_4409097
CYP1A2	5.3	AC50	5012	nM	CHEMBL_ACT_6011998
AKR1C3	5.23	IC50	5900	nM	CHEMBL_ACT_18881578
AKR1C2	5.17	IC50	6710	nM	CHEMBL_ACT_18881573
KDM1A	5.16	IC50	6970	nM	CHEMBL_ACT_24662261
BCHE	5.15	IC50	7010	nM	CHEMBL_ACT_29092628
SMN1	5.15	Potency	7080	nM	CHEMBL_ACT_3862104
P81908	5.03	IC50	9400	nM	CHEMBL_ACT_18255052
P0A031	5	IC50	10000	nM	CHEMBL_ACT_25003751

Target pathways

Aggregated over 2 target gene(s): CYP1B1, CYP2D6.

Top Reactome pathways

10 total, by targets touching each:

Pathway	Targets	Genes
Fatty acids	1	CYP2D6
Miscellaneous substrates	1	CYP2D6
Endogenous sterols	1	CYP1B1
Xenobiotics	1	CYP2D6
CYP2E1 reactions	1	CYP2D6
Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET)	1	CYP1B1
Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE)	1	CYP1B1
Defective CYP1B1 causes Glaucoma	1	CYP1B1
Biosynthesis of maresin-like SPMs	1	CYP2D6
Aspirin ADME	1	CYP2D6

Dominant GO biological processes

GO term	Targets
xenobiotic metabolic process	2
steroid metabolic process	2
estrogen metabolic process	2
arachidonate metabolic process	2
xenobiotic catabolic process	2
retinol metabolic process	2
lipid metabolic process	2
fatty acid metabolic process	2
angiogenesis	1
trabecular meshwork development	1
steroid catabolic process	1
nitric oxide biosynthetic process	1
cell adhesion	1
negative regulation of cell population proliferation	1
intrinsic apoptotic signaling pathway in response to oxidative stress	1

Indications & clinical

Indications

6 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
type 2 diabetes mellitus	3	MONDO:0005148	MONDO:0005148
metabolic dysfunction-associated steatotic liver disease	2	MONDO:0013209	EFO:0003095
colorectal adenoma	2	MONDO:0005484	EFO:0005406
prediabetes syndrome	2	MONDO:0006920	EFO:1001121
lung adenocarcinoma	2	MONDO:0005061	EFO:0000571

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

Clinical trials

Total trials: 61.

Phase distribution

Phase	Trials
Not specified	30
PHASE4	16
PHASE3	4
PHASE2/PHASE3	3
PHASE1/PHASE2	2
PHASE2	2
PHASE1	2
EARLY_PHASE1	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03378934	PHASE4	RECRUITING	Anti-platelet Effect of Berberine in Patients After Percutaneous Coronary Intervention
NCT04698330	PHASE4	NOT_YET_RECRUITING	Effects Of Berberine Plus Inulin On Diabetes Care in Patients With LADA
NCT05105321	PHASE4	NOT_YET_RECRUITING	Cardiovascular Diseases and Diabetes Prevention Programme in Metabolic Syndrome (CDPP)
NCT02296021	PHASE4	COMPLETED	Helicobacter Pylori Eradication With Berberine Quadruple Therapy Versus Bismuth-containing Quadruple Therapy
NCT02633930	PHASE4	COMPLETED	Helicobacter Pylori Eradication With Berberine Quadruple Therapy Versus Clarithromycin Quadruple Therapy
NCT02808351	PHASE4	COMPLETED	Berberine Prevent Contrast-induced Nephropathy in Patients With Diabetes
NCT02962245	PHASE4	WITHDRAWN	Efficacy of Treatment With Berberine to Maintain Remission in Ulcerative Colitis
NCT03029390	PHASE4	UNKNOWN	Effect of Berberine Versus Metformin on Glycemic Control, Insulin Sensitivity and Insulin Secretion in Prediabetes
NCT03198572	PHASE4	UNKNOWN	Efficacy and Safety of Berberine in Non-alcoholic Steatohepatitis
NCT03609892	PHASE4	COMPLETED	Helicobacter Rescue Therapy With Berberine Plus Amoxicillin Quadruple Therapy Versus Tetracycline Plus Furazolidone Quadruple Therapy
NCT03708549	PHASE4	UNKNOWN	Comparison of Berberine and Metformin for the Treatment for MS in Schizophrenia Patients
NCT04479202	PHASE4	COMPLETED	The Effect of Berberine on Intestinal Function and Inflammatory Mediators in Severe Patients With Covid-19
NCT04697186	PHASE4	COMPLETED	Helicobacter Pylori Eradication With Berberine Plus Amoxicillin Triple Therapy Versus Bismuth-containing Quadruple Therapy
NCT05014334	PHASE4	COMPLETED	Study on The Efficacy and Safety of Berberine-containing Triple Therapy in Helicobacter Pylori First-Line Eradication
NCT06514274	PHASE4	COMPLETED	Study on The Efficacy and Safety of Vonoprazan-containing Berberine Triple Therapy in Helicobacter Pylori First-Line Eradication
NCT06603688	PHASE4	UNKNOWN	Study on the Efficacy and Safety of Berberine, Minocycline, Esomeprazole, and Colloidal Bismuth Quadruple Therapy in the Initial Treatment of Helicobacter Pylori.
NCT06782646	PHASE2/PHASE3	ENROLLING_BY_INVITATION	Study on the Sex-specific, Lipid- and Lipoprotein-lowering Effects of Berberine
NCT00462046	PHASE3	COMPLETED	Efficacy and Safety of Berberine in the Treatment of Diabetes With Dyslipidemia
NCT02548832	PHASE3	COMPLETED	Bezafibrate Plus Berberine in Mixed Dyslipidemia
NCT02983188	PHASE2/PHASE3	COMPLETED	Berberine as Adjuvant Treatment for Schizophrenia Patients
NCT03770325	PHASE2/PHASE3	COMPLETED	A Mechanistic Randomized Controlled Trial on the Cardiovascular Effect of Berberine
NCT04543643	PHASE3	UNKNOWN	Endoscopic and Microbiological Assessment of the Effect of Carvedilol Combined With Berberine on GOV in Cirrhosis
NCT04860063	PHASE3	UNKNOWN	Effect of Berberine on Metabolic Syndrome, Efficacy and Safety in Combination With Antiretroviral Therapy in PLWH.
NCT00425009	PHASE1/PHASE2	COMPLETED	Therapeutic Effects of Berberine in Patients With Type 2 Diabetes
NCT00633282	PHASE2	COMPLETED	Role of Pioglitazone and Berberine in Treatment of Non-Alcoholic Fatty Liver Disease
NCT03486496	PHASE2	UNKNOWN	Gefitinib and Berberine in the First-line Treatment of Lung Adenocarcinoma With EGFR Mutation
NCT04434365	PHASE1/PHASE2	UNKNOWN	Effect of Berberine for Endothelial Function and Intestinal Microflora in Patients With Coronary Artery Disease
NCT04918667	PHASE1	NOT_YET_RECRUITING	Effect of Gamma-cyclodextrin on the Bioavailability of Berberine
NCT02365480	PHASE1	COMPLETED	Berberine Chloride in Preventing Colorectal Cancer in Patients With Ulcerative Colitis in Remission
NCT03972215	EARLY_PHASE1	COMPLETED	Berberine Hyperglycemic Clamp
NCT05947370	EARLY_PHASE1	COMPLETED	Berberine on the Secretion of Incretin
NCT06911983	Not specified	NOT_YET_RECRUITING	Comparative Efficacy of Metformin and Berberine Among TCF7L2 (rs7903146) TT vs. CC Genotype Carriers With Type 2 Diabetes
NCT07356765	Not specified	ENROLLING_BY_INVITATION	Berberine in Treating Negative Symptoms of Schizophrenia: Clinical Efficacy and Mechanisms
NCT07359209	Not specified	ENROLLING_BY_INVITATION	Berberine Improving Cognitive Impairments in Schizophrenia
NCT07420231	Not specified	RECRUITING	Evaluation of the Synergistic Effect of Combining a Prebiotic and a Postbiotic on Intestinal Discomfort
NCT07480018	Not specified	ACTIVE_NOT_RECRUITING	Berberine Supplementation, Sprint Interval Training, and Immune Function Study
NCT07541898	Not specified	NOT_YET_RECRUITING	Effects of Berberine on Cardiometabolic Outcomes
NCT01116167	Not specified	UNKNOWN	Polycystic Ovary Syndrome (PCOS): Effect Of Letrozole and Berberine
NCT01138930	Not specified	UNKNOWN	Effect of Berberine on Hormonal and Metabolic Features in Obese Women With Polycystic Ovary Syndrome (PCOS)
NCT02936414	Not specified	COMPLETED	Berberine Effect on Cytokine, CRP, Metabolic Disturbance as an Adjunctive Therapy in Schizophrenia Patients

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 1 clinical and 6 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

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.

439 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
Clozapine	ChEMBL + PubChem	Phase 4 (approved)	CYP1B1, CYP2D6
PAZOPANIB	ChEMBL + PubChem	Phase 4 (approved)	CYP1B1, CYP2D6
CANNABIDIOL	ChEMBL	Phase 4 (approved)	CYP1B1, CYP2D6
MELATONIN	ChEMBL	Phase 4 (approved)	CYP1B1, CYP2D6
BERGAPTEN	ChEMBL	Phase 3	CYP1B1, CYP2D6
QUERCETIN	ChEMBL	Phase 3	CYP1B1, CYP2D6
BAICALEIN	ChEMBL	Phase 2	CYP1B1, CYP2D6
FORMONONETIN	ChEMBL	Phase 2	CYP1B1, CYP2D6
KHELLIN	ChEMBL	Phase 2	CYP1B1, CYP2D6
LUTEOLIN	ChEMBL	Phase 2	CYP1B1, CYP2D6
ERYTHROMYCIN	ChEMBL + PubChem	Phase 4 (approved)	CYP1B1
MAVORIXAFOR	ChEMBL + PubChem	Phase 4 (approved)	CYP2D6
AMBENONIUM	ChEMBL	Phase 4 (approved)	CYP2D6
AMILORIDE	ChEMBL	Phase 4 (approved)	CYP2D6
AMIODARONE	ChEMBL	Phase 4 (approved)	CYP2D6
AMITRIPTYLINE	ChEMBL	Phase 4 (approved)	CYP2D6
AMODIAQUINE	ChEMBL	Phase 4 (approved)	CYP2D6
AMOXAPINE	ChEMBL	Phase 4 (approved)	CYP2D6
AMSACRINE	ChEMBL	Phase 4 (approved)	CYP2D6
ANTAZOLINE	ChEMBL	Phase 4 (approved)	CYP2D6
APOMORPHINE	ChEMBL	Phase 4 (approved)	CYP2D6
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	CYP2D6
ATOMOXETINE	ChEMBL	Phase 4 (approved)	CYP2D6
AZELASTINE	ChEMBL	Phase 4 (approved)	CYP2D6
BENOXINATE	ChEMBL	Phase 4 (approved)	CYP2D6
BENPERIDOL	ChEMBL	Phase 4 (approved)	CYP2D6
BENZNIDAZOLE	ChEMBL	Phase 4 (approved)	CYP2D6
BENZTHIAZIDE	ChEMBL	Phase 4 (approved)	CYP2D6
BENZYDAMINE	ChEMBL	Phase 4 (approved)	CYP2D6
BETAXOLOL	ChEMBL	Phase 4 (approved)	CYP2D6
BRETYLIUM TOSYLATE	ChEMBL	Phase 4 (approved)	CYP2D6
BRIMONIDINE	ChEMBL	Phase 4 (approved)	CYP2D6
BROMHEXINE	ChEMBL	Phase 4 (approved)	CYP2D6
BROMPERIDOL	ChEMBL	Phase 4 (approved)	CYP2D6
BUFEXAMAC	ChEMBL	Phase 4 (approved)	CYP2D6
BUFLOMEDIL	ChEMBL	Phase 4 (approved)	CYP2D6
BUPIVACAINE	ChEMBL	Phase 4 (approved)	CYP2D6
BUSPIRONE	ChEMBL	Phase 4 (approved)	CYP2D6
BUTENAFINE	ChEMBL	Phase 4 (approved)	CYP2D6
CARBETAPENTANE	ChEMBL	Phase 4 (approved)	CYP2D6
CARVEDILOL	ChEMBL	Phase 4 (approved)	CYP1B1
CELECOXIB	ChEMBL	Phase 4 (approved)	CYP2D6
CHLORAMBUCIL	ChEMBL	Phase 4 (approved)	CYP2D6
CHLORHEXIDINE	ChEMBL	Phase 4 (approved)	CYP2D6
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	CYP2D6
CIMETIDINE	ChEMBL	Phase 4 (approved)	CYP2D6
CINACALCET	ChEMBL	Phase 4 (approved)	CYP2D6
CISAPRIDE	ChEMBL	Phase 4 (approved)	CYP2D6
CLEMASTINE	ChEMBL	Phase 4 (approved)	CYP2D6
CLOFAZIMINE	ChEMBL	Phase 4 (approved)	CYP2D6
CLOMETHIAZOLE	ChEMBL	Phase 4 (approved)	CYP2D6
CLOMIPHENE	ChEMBL	Phase 4 (approved)	CYP2D6
CLOMIPRAMINE	ChEMBL	Phase 4 (approved)	CYP2D6
CLONIDINE	ChEMBL	Phase 4 (approved)	CYP2D6
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	CYP2D6
COBICISTAT	ChEMBL	Phase 4 (approved)	CYP2D6
COLCHICINE	ChEMBL	Phase 4 (approved)	CYP2D6
CYCLIZINE	ChEMBL	Phase 4 (approved)	CYP2D6
CYCLOBENZAPRINE	ChEMBL	Phase 4 (approved)	CYP2D6
CYPROHEPTADINE	ChEMBL	Phase 4 (approved)	CYP2D6