This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.
Explore a selection of our essential drug information below, or:
Identification
- Generic Name
- Bardoxolone
- DrugBank Accession Number
- DB12651
- Background
Bardoxolone has been used in trials studying the treatment of LYMPHOMA and Solid Tumors. It is a synthetic triterpenoid and a highly potent activator of redox-sensitive signaling pathways that induce programmed cell death (apoptosis) in cancer cells that are under high levels of intrinsic oxidative stress. In contrast, Bardoxolone in normal cells induces protective antioxidant/anti-inflammatory responses.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
Structure for Bardoxolone (DB12651)
- Weight
- Average: 491.672
Monoisotopic: 491.303558804 - Chemical Formula
- C31H41NO4
- Synonyms
- Bardoxolone
- External IDs
- CDDO
- RTA 401
- RTA-401
Pharmacology
- Indication
Not Available
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Not Available
- Mechanism of action
Bardoxolone, a synthetic triterpenoid, is a highly potent activator of redox-sensitive signaling pathways that induce programmed cell death (apoptosis) in cancer cells that are under high levels of intrinsic oxidative stress. In contrast, Bardoxolone in normal cells induces protective antioxidant/anti-inflammatory responses. Intensive research in animal models of human cancer has demonstrated that Bardoxolone is a potent anticancer agent with a well-characterized ability to inhibit growth and cause regression of tumors as a single agent and in combination with radiation and chemotherapy. Bardoxolone also suppresses radiation- and chemotherapy-induced damage (e.g., oral mucositis) in normal tissues at dose levels that also produce an anti-cancer effect. Bardoxolone induces apoptosis through both caspase-independent and -dependent mechanisms, the latter involving caspase-8 activation, Bid cleavage, cytochrome c release, and caspase-3 activation. Furthermore, JNK, p38, and ERK pathways are involved in Bardoxolone-induced apoptosis of tumor cell lines mediated by disrupted intracellular redox balance and involving decreased glutathione and increased reactive oxygen species. Study shows that Bardoxolone enhances p42 CEBPA protein at the level of translation. 1
Target Actions Organism ANitric oxide synthase, inducible inhibitorHumans UCaspase-8 Not Available Humans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
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Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- Not Available
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as cyclohexenones. These are compounds containing a cylohexenone moiety, which is a six-membered aliphatic ring that carries a ketone and has one endocyclic double bond.
- Kingdom
- Organic compounds
- Super Class
- Organic oxygen compounds
- Class
- Organooxygen compounds
- Sub Class
- Carbonyl compounds
- Direct Parent
- Cyclohexenones
- Alternative Parents
- Nitriles / Monocarboxylic acids and derivatives / Carboxylic acids / Organopnictogen compounds / Organic oxides / Hydrocarbon derivatives
- Substituents
- Aliphatic homopolycyclic compound / Carbonitrile / Carboxylic acid / Carboxylic acid derivative / Cyclohexenone / Hydrocarbon derivative / Monocarboxylic acid or derivatives / Nitrile / Organic nitrogen compound / Organic oxide
- Molecular Framework
- Aliphatic homopolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 7HT68L8941
- CAS number
- 218600-44-3
- InChI Key
- TXGZJQLMVSIZEI-UQMAOPSPSA-N
- InChI
- 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
- IUPAC Name
- (4aS,6aR,6bS,8aR,12aS,14aR,14bS)-11-cyano-2,2,6a,6b,9,9,12a-heptamethyl-10,14-dioxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,12a,14,14a,14b-octadecahydropicene-4a-carboxylic acid
- SMILES
- CC1(C)CC[C@@]2(CC[C@]3(C)[C@@H]([C@@H]2C1)C(=O)C=C1[C@@]2(C)C=C(C#N)C(=O)C(C)(C)[C@@H]2CC[C@@]31C)C(O)=O
References
- General References
- Koschmieder S, D'Alo F, Radomska H, Schoneich C, Chang JS, Konopleva M, Kobayashi S, Levantini E, Suh N, Di Ruscio A, Voso MT, Watt JC, Santhanam R, Sargin B, Kantarjian H, Andreeff M, Sporn MB, Perrotti D, Berdel WE, Muller-Tidow C, Serve H, Tenen DG: CDDO induces granulocytic differentiation of myeloid leukemic blasts through translational up-regulation of p42 CCAAT enhancer binding protein alpha. Blood. 2007 Nov 15;110(10):3695-705. Epub 2007 Aug 1. [Article]
- External Links
- PubChem Compound
- 400010
- PubChem Substance
- 347828858
- ChemSpider
- 354529
- ChEMBL
- CHEMBL1093059
- ZINC
- ZINC000006019135
- Wikipedia
- Bardoxolone_methyl
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
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Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Not Available
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.00401 mg/mL ALOGPS logP 5.39 ALOGPS logP 6.4 Chemaxon logS -5.1 ALOGPS pKa (Strongest Acidic) 4.6 Chemaxon pKa (Strongest Basic) -5.3 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 95.23 Å2 Chemaxon Rotatable Bond Count 1 Chemaxon Refractivity 139.59 m3·mol-1 Chemaxon Polarizability 56.02 Å3 Chemaxon Number of Rings 5 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0006-0000900000-17893a4f56c11df7472f Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0006-0000900000-7cd145e1e7c4a1342924 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0006-0000900000-35f907ff49e358d10a40 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-00xv-2133900000-1abe03678cb1efba6c67 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-03kd-0000900000-0cd011945e40756915f7 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-00xr-1729600000-b9befd8e41ddec34ce85 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 213.61937 predictedDeepCCS 1.0 (2019) [M+H]+ 215.44427 predictedDeepCCS 1.0 (2019) [M+Na]+ 221.19992 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body (PubMed:7504305, PubMed:7531687, PubMed:7544004, PubMed:7682706). In macrophages, NO mediates tumoricidal and bactericidal actions. Also has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such PTGS2/COX2 (By similarity). As component of the iNOS-S100A8/9 transnitrosylase complex involved in the selective inflammatory stimulus-dependent S-nitrosylation of GAPDH on 'Cys-247' implicated in regulation of the GAIT complex activity and probably multiple targets including ANXA5, EZR, MSN and VIM (PubMed:25417112). Involved in inflammation, enhances the synthesis of pro-inflammatory mediators such as IL6 and IL8 (PubMed:19688109)
- Specific Function
- arginine binding
- Gene Name
- NOS2
- Uniprot ID
- P35228
- Uniprot Name
- Nitric oxide synthase, inducible
- Molecular Weight
- 131116.3 Da
References
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Thiol protease that plays a key role in programmed cell death by acting as a molecular switch for apoptosis, necroptosis and pyroptosis, and is required to prevent tissue damage during embryonic development and adulthood (PubMed:23516580, PubMed:35338844, PubMed:35446120, PubMed:8681376, PubMed:8681377, PubMed:8962078, PubMed:9006941, PubMed:9184224). Initiator protease that induces extrinsic apoptosis by mediating cleavage and activation of effector caspases responsible for FAS/CD95-mediated and TNFRSF1A-induced cell death (PubMed:23516580, PubMed:35338844, PubMed:35446120, PubMed:8681376, PubMed:8681377, PubMed:8962078, PubMed:9006941, PubMed:9184224). Cleaves and activates effector caspases CASP3, CASP4, CASP6, CASP7, CASP9 and CASP10 (PubMed:16916640, PubMed:8962078, PubMed:9006941). Binding to the adapter molecule FADD recruits it to either receptor FAS/TNFRSF6 or TNFRSF1A (PubMed:8681376, PubMed:8681377). The resulting aggregate called the death-inducing signaling complex (DISC) performs CASP8 proteolytic activation (PubMed:9184224). The active dimeric enzyme is then liberated from the DISC and free to activate downstream apoptotic proteases (PubMed:9184224). Proteolytic fragments of the N-terminal propeptide (termed CAP3, CAP5 and CAP6) are likely retained in the DISC (PubMed:9184224). In addition to extrinsic apoptosis, also acts as a negative regulator of necroptosis: acts by cleaving RIPK1 at 'Asp-324', which is crucial to inhibit RIPK1 kinase activity, limiting TNF-induced apoptosis, necroptosis and inflammatory response (PubMed:31827280, PubMed:31827281). Also able to initiate pyroptosis by mediating cleavage and activation of gasdermin-C and -D (GSDMC and GSDMD, respectively): gasdermin cleavage promotes release of the N-terminal moiety that binds to membranes and forms pores, triggering pyroptosis (PubMed:32929201, PubMed:34012073). Initiates pyroptosis following inactivation of MAP3K7/TAK1 (By similarity). Also acts as a regulator of innate immunity by mediating cleavage and inactivation of N4BP1 downstream of TLR3 or TLR4, thereby promoting cytokine production (By similarity). May participate in the Granzyme B (GZMB) cell death pathways (PubMed:8755496). Cleaves PARP1 and PARP2 (PubMed:8681376). Independent of its protease activity, promotes cell migration following phosphorylation at Tyr-380 (PubMed:18216014, PubMed:27109099)
- Specific Function
- cysteine-type endopeptidase activity
- Gene Name
- CASP8
- Uniprot ID
- Q14790
- Uniprot Name
- Caspase-8
- Molecular Weight
- 55390.53 Da
Drug created at October 20, 2016 23:27 / Updated at August 26, 2024 19:22