Bardoxolone Methyl

Summary

Bardoxolone Methyl (CHEMBL1762621) is a phase-3 clinical-stage small molecule targeting PPARG; indicated across 12 conditions including diabetic kidney disease and pulmonary arterial hypertension.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 1 (PPARG)
• Indications: 12 conditions
• Clinical trials: 27
• Chemistry: 505.7 Da · C32H43NO4

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1762621
Name	Bardoxolone Methyl
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	400769
Molecular formula	C32H43NO4
Molecular weight	505.7
InChIKey	WPTTVJLTNAWYAO-KPOXMGGZSA-N

SMILES: C[C@@]12CC[C@]3(CCC(C[C@H]3[C@H]1C(=O)C=C4[C@]2(CC[C@@H]5[C@@]4(C=C(C(=O)C5(C)C)C#N)C)C)(C)C)C(=O)OC

IUPAC name: methyl (4aS,6aR,6bS,8aR,12aS,14aR,14bS)-11-cyano-2,2,6a,6b,9,9,12a-heptamethyl-10,14-dioxo-1,3,4,5,6,7,8,8a,14a,14b-decahydropicene-4a-carboxylate

Also known as: Bardoxolone methyl, Bardoxolone methyl ester, CDDO-METHYL ESTER, CDDO-Me, NSC 713200, NSC-713200, RTA 402, Rta-402, RTA-402, RTA402, SID532003, bardoxolone methyl

Patent coverage: 427 distinct patent families (1,032 SureChEMBL compound mentions), from 1 matched compound structure(s). 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
PPARG	Peroxisome proliferator-activated receptor-γ	Antagonist	6.9	2.6%	P37231

Broader ChEMBL bioactivity targets: 7 (assay-derived). Sample: Nuclear factor erythroid 2-related factor 2, Membrane-bound ghrelin O-acyltransferase MBOAT4, Ubiquitin carboxyl-terminal hydrolase 2, Ubiquitin carboxyl-terminal hydrolase 7, Membrane-bound ghrelin O-acyltransferase MBOAT4, Signal transducer and activator of transcription 3, Replicase polyprotein 1ab.

Bioactivity

ChEMBL activities: 5 potent at pChembl ≥ 5 of 8 total. Top 100 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
P0C7A3	7.46	IC50	35	nM	CHEMBL_ACT_19491062
NFE2L2	7.22	EC50	60	nM	CHEMBL_ACT_18516508
STAT3	5.62	IC50	2380	nM	CHEMBL_ACT_18516489
P0DTD1	5.24	IC50	5810	nM	CHEMBL_ACT_25952158
MBOAT4	5.22	IC50	6000	nM	CHEMBL_ACT_25908860

Target pathways

Aggregated over 1 target gene(s): PPARG.

Top Reactome pathways

8 total, by targets touching each:

Pathway	Targets	Genes
PPARA activates gene expression	1	PPARG
Transcriptional regulation of white adipocyte differentiation	1	PPARG
Nuclear Receptor transcription pathway	1	PPARG
SUMOylation of intracellular receptors	1	PPARG
Regulation of PTEN gene transcription	1	PPARG
MECP2 regulates transcription factors	1	PPARG
MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis	1	PPARG
Transcriptional regulation of brown and beige adipocyte differentiation by EBF2	1	PPARG

Dominant GO biological processes

GO term	Targets
negative regulation of transcription by RNA polymerase II	1
placenta development	1
regulation of transcription by RNA polymerase II	1
fatty acid metabolic process	1
response to nutrient	1
regulation of blood pressure	1
hormone-mediated signaling pathway	1
positive regulation of gene expression	1
negative regulation of gene expression	1
negative regulation of macrophage derived foam cell differentiation	1
positive regulation of cholesterol efflux	1
negative regulation of cholesterol storage	1
negative regulation of lipid storage	1
long-chain fatty acid transport	1
negative regulation of angiogenesis	1

Indications & clinical

Indications

12 diseases in clinical trials (phase 1–3, investigational — not approved indications). Highest ChEMBL trial phase per disease; a non-cancer approved use is occasionally logged at phase 3 here.

Disease (in trials)	Phase	MONDO	EFO
diabetic kidney disease	3	MONDO:0005016	EFO:0000401
pulmonary arterial hypertension	3	MONDO:0015924	EFO:0001361
pulmonary hypertension	3	MONDO:0005149	MONDO:0005149
autosomal dominant polycystic kidney disease	3	MONDO:0004691	EFO:1001496
melanoma	2	MONDO:0005105	EFO:0000756
chronic kidney disease	2	MONDO:0005300	EFO:0003884
severe acute respiratory syndrome	2	MONDO:0005091	MONDO:0100096
hereditary nephritis	2	MONDO:0005334	MONDO:0018965
liver disorder	1	MONDO:0005154	EFO:0001421
lymphoid neoplasm	1	MONDO:0005157	EFO:0001642
exocrine pancreatic carcinoma	1	MONDO:0005192	EFO:0002618
neoplasm	1	MONDO:0005070	EFO:0000616

Clinical trials

Total trials: 27.

Phase distribution

Phase	Trials
PHASE1	13
PHASE2	8
PHASE3	4
PHASE2/PHASE3	1
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02657356	PHASE3	TERMINATED	Bardoxolone Methyl in Patients With Connective Tissue Disease-associated Pulmonary Arterial Hypertension - CATALYST
NCT03019185	PHASE2/PHASE3	COMPLETED	A Phase 2/3 Trial of the Efficacy and Safety of Bardoxolone Methyl in Patients With Alport Syndrome - CARDINAL
NCT03068130	PHASE3	TERMINATED	Extended Access Program to Assess Long-term Safety of Bardoxolone Methyl in Patients With Pulmonary Hypertension RANGER
NCT03550443	PHASE3	TERMINATED	A Phase 3 Study of Bardoxolone Methyl in Patients With Diabetic Kidney Disease; AYAME Study
NCT03749447	PHASE3	TERMINATED	An Extended Access Program for Bardoxolone Methyl in Patients With CKD (EAGLE)
NCT00550849	PHASE1/PHASE2	TERMINATED	Study to Assess the Safety, Tolerability, and Pharmacodynamics of RTA 402 in Patients With Hepatic Dysfunction
NCT01572610	PHASE2	TERMINATED	A Glomerular Filtration Rate (GFR) Measuring Study of RTA 402 in Chronic Kidney Disease (CKD) Patients With Type 2 Diabetes Mellitus
NCT01574365	PHASE2	TERMINATED	A Study of RTA 402 in Chronic Kidney Disease (CKD) Patients With Type 2 Diabetes Mellitus
NCT01576887	PHASE2	WITHDRAWN	A Double-Blind, Randomized, Placebo-Controlled Safety Study Evaluating the Effects of Residual Renal Function (RFF) in Patients With End-Stage Renal Disease and Type 2 Diabetes Mellitus on Peritoneal Dialysis
NCT01655186	PHASE2	WITHDRAWN	A Double-Blind, Randomized, Placebo-Controlled Study Evaluating the Effects of Bardoxolone Methyl on Body Composition in Patients With Stage 4 Chronic Kidney Disease and Type 2 Diabetes Mellitus
NCT02036970	PHASE2	COMPLETED	Bardoxolone Methyl Evaluation in Patients With Pulmonary Hypertension (PH) - LARIAT
NCT02316821	PHASE2	COMPLETED	The Phase II Study of Bardoxolone Methyl in Patients With Chronic Kidney Disease and Type 2 Diabetes; TSUBAKI Study
NCT03366337	PHASE2	COMPLETED	A Phase 2 Trial of the Safety and Efficacy of Bardoxolone Methyl in Patients With Rare Chronic Kidney Diseases - PHOENIX
NCT04494646	PHASE2	COMPLETED	BARCONA: A Study of Effects of Bardoxolone Methyl in Participants With SARS-Corona Virus-2 (COVID-19)
NCT00508807	PHASE1	COMPLETED	RTA 402 in Advanced Solid Tumors or Lymphoid Malignancies
NCT00529113	PHASE1	TERMINATED	Study With Gemcitabine and RTA 402 for Patients With Unresectable Pancreatic Cancer
NCT00529438	PHASE1	COMPLETED	RTA 402 in Patients With Advanced Solid Tumors or Lymphoid Malignancies
NCT01461161	PHASE1	COMPLETED	A Single-Dose, Open-Label, Randomized, Food Effect and Blinded, Randomized, Dose Proportionality Study in Healthy Volunteers With Bardoxolone Methyl
NCT01500798	PHASE1	TERMINATED	A Pharmacodynamic Study of Measured Glomerular Filtration Rate in Patients With Chronic Kidney Disease and Type 2 Diabetes
NCT01503866	PHASE1	COMPLETED	A Phase I Study to Investigate the Absorption, Metabolism and Excretion in Healthy Male Subjects
NCT01549769	PHASE1	TERMINATED	Pharmacokinetic and Pharmacodynamic Study of Bardoxolone Methyl in Patients With Chronic Kidney Disease and Type 2 Diabetes
NCT01551446	PHASE1	WITHDRAWN	Pilot Assessment of the Effects of Bardoxolone Methyl on Renal Perfusion, Systemic Haemodynamics and Cardiac Function in Patients With Chronic Kidney Disease and Type 2 Diabetes
NCT01563562	PHASE1	COMPLETED	Single-Dose, Open-Label Pharmacokinetic Study of Bardoxolone Methyl in Subjects With Mild, Moderate, and Severe Hepatic Impairment and Normal Hepatic Function
NCT01689116	PHASE1	COMPLETED	Multiple-Dose Study of Effect of Bardoxolone Methyl on QT/QTC Interval Volunteers
NCT03264079	PHASE1	COMPLETED	Effect of Itraconazole on the Pharmacokinetics of Bardoxolone Methyl in Healthy Adults
NCT04018339	PHASE1	COMPLETED	A Study of RTA 402 in Obese Adults
NCT04023903	PHASE1	COMPLETED	A Clinical Pharmacology Study of Bardoxolone Methyl in Healthy Adults

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.

84 molecules share ≥1 primary target. Top 84 by shared-target count:

Molecule	Source	Status	Shared targets
FULVESTRANT	ChEMBL + PubChem	Phase 4 (approved)	PPARG
BENZBROMARONE	ChEMBL	Phase 4 (approved)	PPARG
BEXAROTENE	ChEMBL	Phase 4 (approved)	PPARG
CANDESARTAN CILEXETIL	ChEMBL	Phase 4 (approved)	PPARG
CANNABIDIOL	ChEMBL	Phase 4 (approved)	PPARG
CARVEDILOL	ChEMBL	Phase 4 (approved)	PPARG
CEFAMANDOLE	ChEMBL	Phase 4 (approved)	PPARG
CEFOTAXIME	ChEMBL	Phase 4 (approved)	PPARG
CEFOXITIN	ChEMBL	Phase 4 (approved)	PPARG
CEFTAZIDIME	ChEMBL	Phase 4 (approved)	PPARG
CEFTRIAXONE	ChEMBL	Phase 4 (approved)	PPARG
CLOBETASOL PROPIONATE	ChEMBL	Phase 4 (approved)	PPARG
EFAVIRENZ	ChEMBL	Phase 4 (approved)	PPARG
ELAFIBRANOR	ChEMBL	Phase 4 (approved)	PPARG
FENOFIBRATE	ChEMBL	Phase 4 (approved)	PPARG
FENOFIBRIC ACID	ChEMBL	Phase 4 (approved)	PPARG
GEMFIBROZIL	ChEMBL	Phase 4 (approved)	PPARG
GLYBURIDE	ChEMBL	Phase 4 (approved)	PPARG
INDOMETHACIN	ChEMBL	Phase 4 (approved)	PPARG
LASOFOXIFENE	ChEMBL	Phase 4 (approved)	PPARG
LEVOTHYROXINE	ChEMBL	Phase 4 (approved)	PPARG
LIOTHYRONINE	ChEMBL	Phase 4 (approved)	PPARG
LUMIRACOXIB	ChEMBL	Phase 4 (approved)	PPARG
MASOPROCOL	ChEMBL	Phase 4 (approved)	PPARG
METHYLENE BLUE	ChEMBL	Phase 4 (approved)	PPARG
MONTELUKAST	ChEMBL	Phase 4 (approved)	PPARG
NINTEDANIB	ChEMBL	Phase 4 (approved)	PPARG
PEMAFIBRATE	ChEMBL	Phase 4 (approved)	PPARG
PIOGLITAZONE	ChEMBL	Phase 4 (approved)	PPARG
RIMONABANT	ChEMBL	Phase 4 (approved)	PPARG
ROSIGLITAZONE	ChEMBL	Phase 4 (approved)	PPARG
SULINDAC	ChEMBL	Phase 4 (approved)	PPARG
TELMISARTAN	ChEMBL	Phase 4 (approved)	PPARG
TERIFLUNOMIDE	ChEMBL	Phase 4 (approved)	PPARG
TIPRANAVIR	ChEMBL	Phase 4 (approved)	PPARG
TROGLITAZONE	ChEMBL	Phase 4 (approved)	PPARG
ZAFIRLUKAST	ChEMBL	Phase 4 (approved)	PPARG
ALEGLITAZAR	ChEMBL	Phase 3	PPARG
BALAGLITAZONE	ChEMBL	Phase 3	PPARG
BEZAFIBRATE	ChEMBL	Phase 3	PPARG
CANDESARTAN	ChEMBL	Phase 3	PPARG
DOCONEXENT	ChEMBL	Phase 3	PPARG
GAMOLENIC ACID	ChEMBL	Phase 3	PPARG
ICOSAPENT	ChEMBL	Phase 3	PPARG
IMIGLITAZAR	ChEMBL	Phase 3	PPARG
LANIFIBRANOR	ChEMBL	Phase 3	PPARG
LERIGLITAZONE	ChEMBL	Phase 3	PPARG
LOBEGLITAZONE	ChEMBL	Phase 3	PPARG
MURAGLITAZAR	ChEMBL	Phase 3	PPARG
NAMODENOSON	ChEMBL	Phase 3	PPARG
QUERCETIN	ChEMBL	Phase 3	PPARG
RESVERATROL	ChEMBL	Phase 3	PPARG
RIVOGLITAZONE	ChEMBL	Phase 3	PPARG
TESAGLITAZAR	ChEMBL	Phase 3	PPARG
TIRATRICOL	ChEMBL	Phase 3	PPARG
ARHALOFENATE	ChEMBL	Phase 2	PPARG
ATX08-001	ChEMBL	Phase 2	PPARG
CANNABIGEROL	ChEMBL	Phase 2	PPARG
CIGLITAZONE	ChEMBL	Phase 2	PPARG
CXA-10	ChEMBL	Phase 2	PPARG
DIHOMO-GAMMA-LINOLENIC ACID	ChEMBL	Phase 2	PPARG
EFATUTAZONE	ChEMBL	Phase 2	PPARG
ENGLITAZONE	ChEMBL	Phase 2	PPARG
FARGLITAZAR	ChEMBL	Phase 2	PPARG
GW501516	ChEMBL	Phase 2	PPARG
GW590735	ChEMBL	Phase 2	PPARG
HALOFENATE	ChEMBL	Phase 2	PPARG
INDEGLITAZAR	ChEMBL	Phase 2	PPARG
INT131	ChEMBL	Phase 2	PPARG
IRX-4204	ChEMBL	Phase 2	PPARG
LINOLEIC ACID	ChEMBL	Phase 2	PPARG
LY-518674	ChEMBL	Phase 2	PPARG
MITOGLITAZONE	ChEMBL	Phase 2	PPARG
MK-0533	ChEMBL	Phase 2	PPARG
NAVEGLITAZAR	ChEMBL	Phase 2	PPARG
OLEIC ACID	ChEMBL	Phase 2	PPARG
PIRINIXIC ACID	ChEMBL	Phase 2	PPARG
RAGAGLITAZAR	ChEMBL	Phase 2	PPARG
REGLITAZAR	ChEMBL	Phase 2	PPARG
Afatinib	PubChem	Approved	PPARG
Apixaban	PubChem	Approved	PPARG
Binimetinib	PubChem	Approved	PPARG
chenodiol	PubChem	Approved	PPARG
Imipenem	PubChem	Approved	PPARG