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Details

Stereochemistry ABSOLUTE
Molecular Formula C31H41NO4
Molecular Weight 491.6615
Optical Activity UNSPECIFIED
Defined Stereocenters 7 / 7
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of BARDOXOLONE

SMILES

[H][C@@]12CC(C)(C)CC[C@@]1(CC[C@]3(C)[C@]2([H])C(=O)C=C4[C@@]5(C)C=C(C#N)C(=O)C(C)(C)[C@]5([H])CC[C@@]34C)C(O)=O

InChI

InChIKey=TXGZJQLMVSIZEI-UQMAOPSPSA-N
InChI=1S/C31H41NO4/c1-26(2)10-12-31(25(35)36)13-11-30(7)23(19(31)16-26)20(33)14-22-28(5)15-18(17-32)24(34)27(3,4)21(28)8-9-29(22,30)6/h14-15,19,21,23H,8-13,16H2,1-7H3,(H,35,36)/t19-,21-,23-,28-,29+,30+,31-/m0/s1

HIDE SMILES / InChI

Molecular Formula C31H41NO4
Molecular Weight 491.6615
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 7 / 7
E/Z Centers 0
Optical Activity UNSPECIFIED

2-Cyano-3,12-dioxooleana-1,9-diene-28-oic acid (CDDO, also known as Bardoxolone) is a synthetic triterpenoid that displays potent anti-inflammatory and antitumorigenic activities. CDDO was in the clinical trial phase I for the treatment patients with Solid tumors and leukemia, but that studies were discontinued. It is known, that CDDO blocks the cellular synthesis of inducible nitric oxide synthase and inducible COX-2. In addition, was discovered, that CDDO disrupted intracellular redox balance and thereby induce apoptosis. Moreover, CDDO is a ligand for peroxisome proliferator-activated receptor that it induces genes regulated by Nrf2, including heme oxygenase-1 and eotaxin-1, which play a role in antioxidant response element signaling activity.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P35228|||Q9UD42
Gene ID: 4843.0
Gene Symbol: NOS2
Target Organism: Homo sapiens (Human)
Target ID: intracellular redox balance
Target ID: P37231|||Q15179
Gene ID: 5468.0
Gene Symbol: PPARG
Target Organism: Homo sapiens (Human)
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
24.7 ng/mL
900 mg 1 times / day steady-state, oral
dose: 900 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
BARDOXOLONE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
28.8 ng/mL
1300 mg 1 times / day steady-state, oral
dose: 1300 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
BARDOXOLONE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
20370 ng × h/mL
900 mg 1 times / day steady-state, oral
dose: 900 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
BARDOXOLONE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
24411 ng × h/mL
1300 mg 1 times / day steady-state, oral
dose: 1300 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
BARDOXOLONE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
39 h
900 mg 1 times / day steady-state, oral
dose: 900 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
BARDOXOLONE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
34 h
1300 mg 1 times / day steady-state, oral
dose: 1300 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
BARDOXOLONE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
1300 mg 1 times / day multiple, oral
Highest studied dose
Dose: 1300 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1300 mg, 1 times / day
Sources: Page: p.7
unhealthy, ADULT
n = 9
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 9
Sources: Page: p.7
DLT: ALT increased...
Dose limiting toxicities:
ALT increased (grade 3, 22.2%)
Sources: Page: p.7
900 mg 1 times / day multiple, oral
MTD
Dose: 900 mg, 1 times / day
Route: oral
Route: multiple
Dose: 900 mg, 1 times / day
Sources: Page: p.7
unhealthy, ADULT
n = 25
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 25
Sources: Page: p.7
AEs

AEs

AESignificanceDosePopulation
ALT increased grade 3, 22.2%
DLT, Disc. AE
1300 mg 1 times / day multiple, oral
Highest studied dose
Dose: 1300 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1300 mg, 1 times / day
Sources: Page: p.7
unhealthy, ADULT
n = 9
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 9
Sources: Page: p.7
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
A synthetic triterpenoid, 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO), is a ligand for the peroxisome proliferator-activated receptor gamma.
2000 Oct
Extremely potent triterpenoid inducers of the phase 2 response: correlations of protection against oxidant and inflammatory stress.
2005 Mar 22
Bardoxolone methyl (BARD) ameliorates aristolochic acid (AA)-induced acute kidney injury through Nrf2 pathway.
2014 Apr 6

Sample Use Guides

In Vitro Use Guide
CDDO induced monocytic differentiation of human myeloid leukemia cells and adipogenic differentiation of mouse 3T3-L1 fibroblasts and enhanced the neuronal differentiation of rat PC12 pheochromocytoma cells caused by nerve growth factor. CDDO inhibited proliferation of many human tumor cell lines, including those derived from estrogen receptor-positive and -negative breast carcinomas, myeloid leukemias, and several carcinomas bearing a Smad4 mutation. Furthermore, it suppressed the abilities of various inflammatory cytokines, such as IFN-gamma, interleukin-1, and tumor necrosis factor-alpha, to induce de novo formation of the enzymes inducible nitric oxide synthase (iNos) and inducible cyclooxygenase (COX-2) in mouse peritoneal macrophages, rat brain microglia, and human colon fibroblasts. The above activities had been found at concentrations ranging from 10(-6) to 10(-9) M in cell culture.
Substance Class Chemical
Created
by admin
on Fri Dec 15 16:05:04 UTC 2023
Edited
by admin
on Fri Dec 15 16:05:04 UTC 2023
Record UNII
7HT68L8941
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
BARDOXOLONE
INN   MI   USAN   WHO-DD  
INN   USAN  
Official Name English
bardoxolone [INN]
Common Name English
2-Cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid
Systematic Name English
RTA401
Code English
CDDO
Code English
OLEANA-1,9(11)-DIEN-28-OIC ACID, 2-CYANO-3,12-DIOXO-
Common Name English
BARDOXOLONE [MI]
Common Name English
RTA-401
Code English
Bardoxolone [WHO-DD]
Common Name English
(+)-2-CYANO-3,12-DIOXOOLEANA-1,9(11)-DIEN-28-OIC ACID
Common Name English
BARDOXOLONE [USAN]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C1323
Created by admin on Fri Dec 15 16:05:04 UTC 2023 , Edited by admin on Fri Dec 15 16:05:04 UTC 2023
NCI_THESAURUS C29574
Created by admin on Fri Dec 15 16:05:04 UTC 2023 , Edited by admin on Fri Dec 15 16:05:04 UTC 2023
FDA ORPHAN DRUG 456114
Created by admin on Fri Dec 15 16:05:04 UTC 2023 , Edited by admin on Fri Dec 15 16:05:04 UTC 2023
FDA ORPHAN DRUG 264108
Created by admin on Fri Dec 15 16:05:04 UTC 2023 , Edited by admin on Fri Dec 15 16:05:04 UTC 2023
Code System Code Type Description
FDA UNII
7HT68L8941
Created by admin on Fri Dec 15 16:05:04 UTC 2023 , Edited by admin on Fri Dec 15 16:05:04 UTC 2023
PRIMARY
USAN
UU-156
Created by admin on Fri Dec 15 16:05:04 UTC 2023 , Edited by admin on Fri Dec 15 16:05:04 UTC 2023
PRIMARY
DRUG BANK
DB12651
Created by admin on Fri Dec 15 16:05:04 UTC 2023 , Edited by admin on Fri Dec 15 16:05:04 UTC 2023
PRIMARY
EPA CompTox
DTXSID001025273
Created by admin on Fri Dec 15 16:05:04 UTC 2023 , Edited by admin on Fri Dec 15 16:05:04 UTC 2023
PRIMARY
NSC
711193
Created by admin on Fri Dec 15 16:05:04 UTC 2023 , Edited by admin on Fri Dec 15 16:05:04 UTC 2023
PRIMARY
SMS_ID
300000000141
Created by admin on Fri Dec 15 16:05:04 UTC 2023 , Edited by admin on Fri Dec 15 16:05:04 UTC 2023
PRIMARY
NCI_THESAURUS
C48382
Created by admin on Fri Dec 15 16:05:04 UTC 2023 , Edited by admin on Fri Dec 15 16:05:04 UTC 2023
PRIMARY
INN
9108
Created by admin on Fri Dec 15 16:05:04 UTC 2023 , Edited by admin on Fri Dec 15 16:05:04 UTC 2023
PRIMARY
CAS
218600-44-3
Created by admin on Fri Dec 15 16:05:04 UTC 2023 , Edited by admin on Fri Dec 15 16:05:04 UTC 2023
PRIMARY
ChEMBL
CHEMBL1093059
Created by admin on Fri Dec 15 16:05:04 UTC 2023 , Edited by admin on Fri Dec 15 16:05:04 UTC 2023
PRIMARY
MERCK INDEX
m2229
Created by admin on Fri Dec 15 16:05:04 UTC 2023 , Edited by admin on Fri Dec 15 16:05:04 UTC 2023
PRIMARY Merck Index
PUBCHEM
400010
Created by admin on Fri Dec 15 16:05:04 UTC 2023 , Edited by admin on Fri Dec 15 16:05:04 UTC 2023
PRIMARY
Related Record Type Details
TARGET -> ACTIVATOR
Related Record Type Details
ACTIVE MOIETY