Probucol

Summary

Probucol (CHEMBL608) is an approved small-molecule anticholesteremic drug (ATC C10AX02) targeting ABCA1; indicated across 4 conditions including cardiovascular disorder and hyperlipidemia.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: C10AX02
• Targets: 1 (ABCA1)
• Indications: 4 conditions
• Clinical trials: 20
• Chemistry: 516.8 Da · C31H48O2S2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL608
Name	Probucol
Type	Small molecule
Max phase	4
FDA approved	no
PubChem CID	4912
ChEBI	CHEBI:8427
ATC	C10AX02
Molecular formula	C31H48O2S2
Molecular weight	516.8
InChIKey	FYPMFJGVHOHGLL-UHFFFAOYSA-N

SMILES: CC(C)(C)C1=CC(=CC(=C1O)C(C)(C)C)SC(C)(C)SC2=CC(=C(C(=C2)C(C)(C)C)O)C(C)(C)C

IUPAC name: 2,6-ditert-butyl-4-[2-(3,5-ditert-butyl-4-hydroxyphenyl)sulfanylpropan-2-ylsulfanyl]phenol

ChEBI definition: A dithioketal that is propane-2,2-dithiol in which the hydrogens attached to both sulfur atoms are replaced by 3,5-di-tert-butyl-4-hydroxyphenyl groups. An anticholesteremic drug with antioxidant and anti-inflammatory properties, it is used to treat high levels of cholesterol in blood.

Pharmacological roles (ChEBI): anticholesteremic drug, antioxidant, anti-inflammatory drug, cardiovascular drug, antilipemic drug.

Also known as: Bisbid, DH-581, Lorelco, Lurselle, NSC-652160, NSC-86225, Probucol, Sinlestal, probucol, SID26748484, SID50107410, SID8139943

Patent coverage: 7,890 distinct patent families (30,435 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 30,434 (100%) 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
ABCA1	ABCA1	Inhibition		0.3%	O95477

Broader ChEMBL bioactivity targets: 5 (assay-derived). Sample: Microtubule-associated protein tau, Serine protease hepsin, NAD-dependent protein deacylase sirtuin-5, mitochondrial, Trypsin, Polyunsaturated fatty acid lipoxygenase ALOX15.

Bioactivity

ChEMBL activities: 4 potent at pChembl ≥ 5 of 6 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
HPN	6.37	IC50	430	nM	CHEMBL_ACT_17720154
SIRT5	5.8	IC50	1600	nM	CHEMBL_ACT_22986893
MAPT	5.15	Potency	7080	nM	CHEMBL_ACT_4504584
MAPT	5	Potency	10000	nM	CHEMBL_ACT_4508751

Target pathways

Aggregated over 1 target gene(s): ABCA1.

Top Reactome pathways

16 total, by targets touching each:

Pathway	Targets	Genes
Metabolism	1	ABCA1
Signal Transduction	1	ABCA1
Disease	1	ABCA1
Plasma lipoprotein assembly, remodeling, and clearance	1	ABCA1
PPARA activates gene expression	1	ABCA1
Transport of small molecules	1	ABCA1
Regulation of lipid metabolism by PPARalpha	1	ABCA1
Metabolism of lipids	1	ABCA1
ABC transporter disorders	1	ABCA1
Disorders of transmembrane transporters	1	ABCA1
Defective ABCA1 causes TGD	1	ABCA1
HDL assembly	1	ABCA1
Plasma lipoprotein assembly	1	ABCA1
Signaling by Nuclear Receptors	1	ABCA1
NR1H2 and NR1H3-mediated signaling	1	ABCA1
NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux	1	ABCA1

Dominant GO biological processes

GO term	Targets
peptide secretion	1
phagocytosis, engulfment	1
lysosome organization	1
G protein-coupled receptor signaling pathway	1
adenylate cyclase-activating G protein-coupled receptor signaling pathway	1
cholesterol metabolic process	1
protein secretion	1
negative regulation of macrophage derived foam cell differentiation	1
positive regulation of cholesterol efflux	1
negative regulation of cholesterol storage	1
endosomal transport	1
signal release	1
intracellular cholesterol transport	1
regulation of Cdc42 protein signal transduction	1
cholesterol efflux	1

Indications & clinical

Indications

4 indications (1 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
cardiovascular disorder	4	MONDO:0004995	EFO:0000319
hyperlipidemia	3	MONDO:0021187	MONDO:0021187
diabetic kidney disease	2	MONDO:0005016	EFO:0000401
peripheral arterial disease	2	MONDO:0005386	EFO:0004265

Clinical trials

Total trials: 20.

Phase distribution

Phase	Trials
PHASE4	11
Not specified	3
PHASE3	2
PHASE2	2
PHASE1/PHASE2	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03753555	PHASE4	RECRUITING	The Effect of InTensive Statin in Ischemic Stroke With inTracranial Atherosclerotic Plaques
NCT00426348	PHASE4	COMPLETED	A Study of the Antioxidant Probucol Combined With Valsartan in Patients With IgA Nephropathy
NCT00549978	PHASE4	COMPLETED	Safety and Pharmacokinetics of Probucol and Cilostazol
NCT00823849	PHASE4	COMPLETED	Study of Cilostazol and Probucol to Assess Their Effects on Atherosclerosis Related Biomarker
NCT00823875	PHASE4	COMPLETED	Study of Cilostazol and Probucol Alone and in Combination on Atherosclerosis Related Biomarker—atherosclerosis Cerebral Infarction Patient as Study Subject
NCT01000467	PHASE4	COMPLETED	Pharmacokinetics Study for Probucol
NCT01013532	PHASE4	UNKNOWN	PreventIon of CArdiovascular Events in iSchemic Stroke Patients With High Risk of Cerebral HemOrrhage
NCT01252056	PHASE4	COMPLETED	A Clinical Study to Evaluate the Efficacy and Safety of Cilostazol and Probucol in Combination on Patients With Diabetic Nephropathy
NCT01291641	PHASE4	COMPLETED	Effect of Probucol and/or Cilostazol on Mean IMT in Patients With Coronary Heart dIsease
NCT02098460	PHASE4	COMPLETED	To Compare the Effect of Concomitant Administration of Probucol and Cilostazol With Probucol Single Treatment on the Atherosclerosis Related Markers (Including the Thickness of the Achilles Tendon) and Evaluate Safety (Based on Atorvastatin Treatment) in Severe Hypercholesterolemia Subject
NCT02483169	PHASE4	UNKNOWN	PreventIon of IMT Progression in iSchemic Stroke Patients With High Risk of Cerebral HemOrrhage-IMT Study
NCT06225752	PHASE3	RECRUITING	Probucol for Symptomatic Intracranial and Extracranial Artery Stenosis
NCT01349010	PHASE3	COMPLETED	Efficacy and Safety of Imported Probucol to Treat Hyperlipidemia
NCT01142284	PHASE2	COMPLETED	Evaluation of Concomitant Administration of Cilostazol and Probucol on Biomarkers, Endothelial Function and Safety
NCT01726816	PHASE2	COMPLETED	Efficacy and Safety Study of Probucol in Patients With Diabetic Nephropathy
NCT02707458	PHASE1/PHASE2	COMPLETED	Dosage and Efficacy of Probucol-induced apoE to Negate Cognitive Deterioration
NCT01590901	PHASE1	COMPLETED	Pharmacokinetics and Safety Study of Probucol by Multiple Administration in Healthy Male Subjects
NCT06604117	Not specified	RECRUITING	Efficacy of Probucol Combined with Statins Treatment for Ischemic Stroke
NCT06931834	Not specified	AVAILABLE	Expanded Access Program for R007 (Probucol) Tablets in Adults With Mitochondrial Disease and Chronic Kidney Disease
NCT00655330	Not specified	UNKNOWN	Probucol Combined With Valsartan in Reducing Proteinuria in Diabetes Nephropathy

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Related molecules

Related molecules

No competitor molecules sharing a primary target (ChEMBL phase ≥2 or PubChem drug-class).