BARDOXOLONE

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 Search

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

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/14500394 | https://clinicaltrials.gov/ct2/show/NCT00322140 | https://www.ncbi.nlm.nih.gov/pubmed/14522919

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

Primary Target	Pharmacology	Condition	Potency
Nitric oxide synthase, inducible 50 Target ID: P35228\|\|\|Q9UD42 Gene ID: 4843.0 Gene Symbol: NOS2 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/9873608	Inhibitor 8297
intracellular redox balance 1 Target ID: intracellular redox balance Sources: https://www.ncbi.nlm.nih.gov/pubmed/14500394	Inhibitor 8297
Peroxisome proliferator-activated receptor gamma 111 Target ID: P37231\|\|\|Q15179 Gene ID: 5468.0 Gene Symbol: PPARG Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/14522919	Activator 1430

Conditions

Condition	Modality	Targets	Highest Phase	Product
Acute myeloid leukemia 136 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15520199	Primary		Phase I 428	Unknown Approved Use Unknown
Solid tumors 145 Sources: https://clinicaltrials.gov/ct2/show/NCT00322140	Primary		Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
24.7 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22634319	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22634319	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

Value	Dose	Co-administered	Analyte	Population
20370 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22634319	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22634319	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
39 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22634319	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22634319	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

Dose	Population	Adverse 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: https://pubmed.ncbi.nlm.nih.gov/22634319 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: https://pubmed.ncbi.nlm.nih.gov/22634319 Page: p.7	DLT: ALT increased... Dose limiting toxicities: ALT increased (grade 3, 22.2%) Sources: https://pubmed.ncbi.nlm.nih.gov/22634319 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: https://pubmed.ncbi.nlm.nih.gov/22634319 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: https://pubmed.ncbi.nlm.nih.gov/22634319 Page: p.7	Sources: https://pubmed.ncbi.nlm.nih.gov/22634319 Page: p.7

AEs

AE	Significance	Dose	Population
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: https://pubmed.ncbi.nlm.nih.gov/22634319 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: https://pubmed.ncbi.nlm.nih.gov/22634319 Page: p.7

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY445253	https://www.001chemical.com/chem/search?q=DY445253
AChemBlock	Q65454	http://www.achemblock.com/catalogsearch/result/?q=Q65454
AK Scientific	3470AH	https://aksci.com/item_detail.php?cat=3470AH
AstaTech	C74085	http://astatechinc.com/CPSResult.php?CRNO=C74085
Axon MedChem	1950	https://www.axonmedchem.com/product/1950
BOC Sciences	218600-44-3	http://www.bocsci.com/description.asp?cas=218600-44-3
Cayman Chemical	81035	http://www.caymanchem.com/app/template/Product.vm/catalog/81035
Chem Scene	CS-0728	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0728
ChemShuttle	140113	https://www.chemshuttle.com/catalogsearch/result/?q=140113
Excenen	EX-A1731	http://www.excenen.com/searchresultlist.php?id=EX-A1731
Lab Network	LN01480764	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01480764
Lab Seeker	SC-94065	http://www.labseeker.com/search.php?keywords=SC-94065&category=0
LabSeeker	SC-94065	http://www.labseeker.com/search.php?keywords=SC-94065&category=0
Life Chemicals	F2197-0016	https://shop.lifechemicals.com/2/F2197-0016
MedChem Express	HY-14909	https://www.medchemexpress.com/search.html?q=HY-14909&ft=&fa=&fp=
MolPort	MolPort-019-922-066	https://www.molport.com/shop/molecule-link/MolPort-019-922-066
MolPort	MolPort-023-219-131	https://www.molport.com/shop/molecule-link/MolPort-023-219-131
MolPort	MolPort-044-561-909	https://www.molport.com/shop/molecule-link/MolPort-044-561-909
Molnova	M17438	https://www.molnova.com/en/serch-list.html?keywords=M17438
ShangHai Biochempartner	BCP000567	http://www.biochempartner.com/search_BCP000567
ShangHai Biochempartner	BCP04662	http://www.biochempartner.com/search_BCP04662
TargetMol	T2915	https://www.targetmol.com/search?keyword=T2915
Toronto Research Chemicals	A164370	https://www.trc-canada.com/product-detail/?CatNum=A164370
Toronto Research Chemicals	B118660	https://www.trc-canada.com/product-detail/?CatNum=B118660
eMolecules	37104789	https://orderbb.emolecules.com/search/#?query=37104789
eMolecules	44786242	https://orderbb.emolecules.com/search/#?query=44786242
eMolecules	45988567	https://orderbb.emolecules.com/search/#?query=45988567
mcule	MCULE-2024719526	https://mcule.com/MCULE-2024719526/
mcule	MCULE-4498813870	https://mcule.com/MCULE-4498813870/

PubMed

Title	Date	PubMed
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	11043571

Sample Use Guides

In Vivo Use Guide

infusion for 5 consecutive days in 28-day cycle

Route of Administration: Intravenous

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.

Name

Type

Language

BARDOXOLONE

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