Idronoxil
Explore a selection of our essential drug information below, or:
Identification
- Generic Name
- Idronoxil
- DrugBank Accession Number
- DB04915
- Background
Idronoxil is a substance that is being studied in the treatment of cancer. It belongs to the family of drugs called signal transduction inhibitors.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
- Weight
- Average: 240.254
Monoisotopic: 240.07864425 - Chemical Formula
- C15H12O3
- Synonyms
- (+/-)-cis-3-(4-hydroxyphenyl)-4-(4-methoxyphenyl)-3,4-dihydro-2H-cromen-7-ol
- 3-(4-hydroxyphenyl)-2H-chromen-7-ol
- Dehydroequol
- Haginin E
- Idronoxil
- Phenoxodiol
- External IDs
- NOX-66
- NV-06
- NV06
Pharmacology
- Indication
Intended for the treatment of various forms of cancer.
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- Pharmacodynamics
Phenoxodiol inhibits proliferation of many cancer cell lines and induces apoptosis by disrupting FLICE-inhibitory protein, FLIP, expression and by caspase-dependent and -independent degradation of the X-linked inhibitor of apoptosis, XIAP. In addition, phenoxodiol sensitizes drug-resistant tumour cells to anticancer drugs including paclitaxel, carboplatin and gemcitabine.
- Mechanism of action
The antiproliferative effects of phenoxodiol are associated with inhibition of plasma membrane electron transport in tumour cell lines and primary immune cells. Results from one study (PMID: 17904534) indicate that plasma membrane electron transport (PMET) may be a primary target for phenoxodiol in tumour cells and in activated T cells.
Target Actions Organism AE3 ubiquitin-protein ligase XIAP modulatorHumans ASphingosine kinase 1 modulatorHumans UEcto-NOX disulfide-thiol exchanger 2 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
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
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 hydroxyisoflavonoids. These are organic compounds containing an isoflavonoid skeleton carrying one or more hydroxyl groups.
- Kingdom
- Organic compounds
- Super Class
- Phenylpropanoids and polyketides
- Class
- Isoflavonoids
- Sub Class
- Hydroxyisoflavonoids
- Direct Parent
- Hydroxyisoflavonoids
- Alternative Parents
- Isoflav-3-enes / 1-benzopyrans / Alkyl aryl ethers / 1-hydroxy-2-unsubstituted benzenoids / Benzene and substituted derivatives / Oxacyclic compounds / Hydrocarbon derivatives
- Substituents
- 1-benzopyran / 1-hydroxy-2-unsubstituted benzenoid / Alkyl aryl ether / Aromatic heteropolycyclic compound / Benzenoid / Benzopyran / Ether / Hydrocarbon derivative / Hydroxyisoflavonoid / Isoflav-3-ene skeleton
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 995FT1W541
- CAS number
- 81267-65-4
- InChI Key
- ZZUBHVMHNVYXRR-UHFFFAOYSA-N
- InChI
- InChI=1S/C15H12O3/c16-13-4-1-10(2-5-13)12-7-11-3-6-14(17)8-15(11)18-9-12/h1-8,16-17H,9H2
- IUPAC Name
- 3-(4-hydroxyphenyl)-2H-chromen-7-ol
- SMILES
- OC1=CC=C(C=C1)C1=CC2=C(OC1)C=C(O)C=C2
References
- General References
- Herst PM, Petersen T, Jerram P, Baty J, Berridge MV: The antiproliferative effects of phenoxodiol are associated with inhibition of plasma membrane electron transport in tumour cell lines and primary immune cells. Biochem Pharmacol. 2007 Dec 3;74(11):1587-95. Epub 2007 Aug 19. [Article]
- Choueiri TK, Wesolowski R, Mekhail TM: Phenoxodiol: isoflavone analog with antineoplastic activity. Curr Oncol Rep. 2006 Mar;8(2):104-7. [Article]
- Mor G, Fu HH, Alvero AB: Phenoxodiol, a novel approach for the treatment of ovarian cancer. Curr Opin Investig Drugs. 2006 Jun;7(6):542-8. [Article]
- Klein R, Brown D, Turnley AM: Phenoxodiol protects against Cisplatin induced neurite toxicity in a PC-12 cell model. BMC Neurosci. 2007 Aug 1;8:61. [Article]
- External Links
- Human Metabolome Database
- HMDB0256416
- PubChem Compound
- 219100
- PubChem Substance
- 175426901
- ChemSpider
- 189918
- BindingDB
- 50419932
- ChEMBL
- CHEMBL1957038
- ZINC
- ZINC000001491943
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample data3 Completed Treatment Abdominal wall neoplasm / Fallopian Tube Cancer / Ovarian Cancer 1 somestatus stop reason just information to hide 2 Completed Treatment Prostate Cancer 1 somestatus stop reason just information to hide 1 Completed Treatment Cancer 1 somestatus stop reason just information to hide 1 Completed Treatment Coronavirus Disease 2019 (COVID‑19) 1 somestatus stop reason just information to hide 1 Completed Treatment Unspecified Adult Solid Tumor, Protocol Specific 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.0693 mg/mL ALOGPS logP 2.82 ALOGPS logP 3.09 Chemaxon logS -3.5 ALOGPS pKa (Strongest Acidic) 8.63 Chemaxon pKa (Strongest Basic) -4.9 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 49.69 Å2 Chemaxon Rotatable Bond Count 1 Chemaxon Refractivity 69.73 m3·mol-1 Chemaxon Polarizability 25.76 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 1.0 Blood Brain Barrier - 0.5249 Caco-2 permeable + 0.7327 P-glycoprotein substrate Substrate 0.5689 P-glycoprotein inhibitor I Non-inhibitor 0.7986 P-glycoprotein inhibitor II Non-inhibitor 0.8194 Renal organic cation transporter Non-inhibitor 0.8197 CYP450 2C9 substrate Non-substrate 0.8351 CYP450 2D6 substrate Non-substrate 0.8967 CYP450 3A4 substrate Non-substrate 0.6399 CYP450 1A2 substrate Inhibitor 0.9043 CYP450 2C9 inhibitor Inhibitor 0.8452 CYP450 2D6 inhibitor Non-inhibitor 0.7896 CYP450 2C19 inhibitor Inhibitor 0.9193 CYP450 3A4 inhibitor Non-inhibitor 0.5889 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.9489 Ames test Non AMES toxic 0.5133 Carcinogenicity Non-carcinogens 0.9184 Biodegradation Not ready biodegradable 0.7429 Rat acute toxicity 2.9655 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9073 hERG inhibition (predictor II) Non-inhibitor 0.8249
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-03dl-0290000000-33f9b71a5a5186eadb99 Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0006-0090000000-375e0872aaa5180afcf0 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-000i-0090000000-bb22976a583c4dbb97aa Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0079-0190000000-5ac8f708ccd8c586189e Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0006-0090000000-eef876d68454075c98bb Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-01ot-0980000000-92f10eddd731c4a90f2e Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0c00-1980000000-0780cad5de2bd8797710 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]- 167.0711252 predictedDarkChem Lite v0.1.0 [M-H]- 167.5529252 predictedDarkChem Lite v0.1.0 [M-H]- 155.30763 predictedDeepCCS 1.0 (2019) [M+H]+ 169.4871252 predictedDarkChem Lite v0.1.0 [M+H]+ 168.0523252 predictedDarkChem Lite v0.1.0 [M+H]+ 157.66563 predictedDeepCCS 1.0 (2019) [M+Na]+ 168.1691252 predictedDarkChem Lite v0.1.0 [M+Na]+ 168.1662252 predictedDarkChem Lite v0.1.0 [M+Na]+ 163.75877 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Modulator
- General Function
- Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, copper homeostasis, mitogenic kinase signaling, cell proliferation, as well as cell invasion and metastasis (PubMed:11257230, PubMed:11257231, PubMed:11447297, PubMed:12121969, PubMed:12620238, PubMed:17560374, PubMed:17967870, PubMed:19473982, PubMed:20154138, PubMed:22103349, PubMed:9230442). Acts as a direct caspase inhibitor (PubMed:11257230, PubMed:11257231, PubMed:12620238). Directly bind to the active site pocket of CASP3 and CASP7 and obstructs substrate entry (PubMed:11257230, PubMed:11257231, PubMed:16352606, PubMed:16916640). Inactivates CASP9 by keeping it in a monomeric, inactive state (PubMed:12620238). Acts as an E3 ubiquitin-protein ligase regulating NF-kappa-B signaling and the target proteins for its E3 ubiquitin-protein ligase activity include: RIPK1, RIPK2, MAP3K2/MEKK2, DIABLO/SMAC, AIFM1, CCS, PTEN and BIRC5/survivin (PubMed:17560374, PubMed:17967870, PubMed:19473982, PubMed:20154138, PubMed:22103349, PubMed:22607974, PubMed:29452636, PubMed:30026309). Acts as an important regulator of innate immunity by mediating 'Lys-63'-linked polyubiquitination of RIPK2 downstream of NOD1 and NOD2, thereby transforming RIPK2 into a scaffolding protein for downstream effectors, ultimately leading to activation of the NF-kappa-B and MAP kinases signaling (PubMed:19667203, PubMed:22607974, PubMed:29452636, PubMed:30026309). 'Lys-63'-linked polyubiquitination of RIPK2 also promotes recruitment of the LUBAC complex to RIPK2 (PubMed:22607974, PubMed:29452636). Regulates the BMP signaling pathway and the SMAD and MAP3K7/TAK1 dependent pathways leading to NF-kappa-B and JNK activation (PubMed:17560374). Ubiquitination of CCS leads to enhancement of its chaperone activity toward its physiologic target, SOD1, rather than proteasomal degradation (PubMed:20154138). Ubiquitination of MAP3K2/MEKK2 and AIFM1 does not lead to proteasomal degradation (PubMed:17967870, PubMed:22103349). Plays a role in copper homeostasis by ubiquitinating COMMD1 and promoting its proteasomal degradation (PubMed:14685266). Can also function as E3 ubiquitin-protein ligase of the NEDD8 conjugation pathway, targeting effector caspases for neddylation and inactivation (PubMed:21145488). Ubiquitinates and therefore mediates the proteasomal degradation of BCL2 in response to apoptosis (PubMed:29020630). Protects cells from spontaneous formation of the ripoptosome, a large multi-protein complex that has the capability to kill cancer cells in a caspase-dependent and caspase-independent manner (PubMed:22095281). Suppresses ripoptosome formation by ubiquitinating RIPK1 and CASP8 (PubMed:22095281). Acts as a positive regulator of Wnt signaling and ubiquitinates TLE1, TLE2, TLE3, TLE4 and AES (PubMed:22304967). Ubiquitination of TLE3 results in inhibition of its interaction with TCF7L2/TCF4 thereby allowing efficient recruitment and binding of the transcriptional coactivator beta-catenin to TCF7L2/TCF4 that is required to initiate a Wnt-specific transcriptional program (PubMed:22304967)
- Specific Function
- cysteine-type endopeptidase inhibitor activity
- Gene Name
- XIAP
- Uniprot ID
- P98170
- Uniprot Name
- E3 ubiquitin-protein ligase XIAP
- Molecular Weight
- 56684.41 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
- Yes
- Actions
- Modulator
- General Function
- Catalyzes the phosphorylation of sphingosine to form sphingosine 1-phosphate (SPP), a lipid mediator with both intra- and extracellular functions. Also acts on D-erythro-sphingosine and to a lesser extent sphinganine, but not other lipids, such as D,L-threo-dihydrosphingosine, N,N-dimethylsphingosine, diacylglycerol, ceramide, or phosphatidylinositol (PubMed:11923095, PubMed:20577214, PubMed:23602659, PubMed:24929359, PubMed:29662056). In contrast to proapoptotic SPHK2, has a negative effect on intracellular ceramide levels, enhances cell growth and inhibits apoptosis (PubMed:16118219). Involved in the regulation of inflammatory response and neuroinflammation. Via the product sphingosine 1-phosphate, stimulates TRAF2 E3 ubiquitin ligase activity, and promotes activation of NF-kappa-B in response to TNF signaling leading to IL17 secretion (PubMed:20577214). In response to TNF and in parallel to NF-kappa-B activation, negatively regulates RANTES induction through p38 MAPK signaling pathway (PubMed:23935096). Involved in endocytic membrane trafficking induced by sphingosine, recruited to dilate endosomes, also plays a role on later stages of endosomal maturation and membrane fusion independently of its kinase activity (PubMed:24929359, PubMed:28049734). In Purkinje cells, seems to be also involved in the regulation of autophagosome-lysosome fusion upon VEGFA (PubMed:25417698)
- Specific Function
- acetyltransferase activity
- Gene Name
- SPHK1
- Uniprot ID
- Q9NYA1
- Uniprot Name
- Sphingosine kinase 1
- Molecular Weight
- 42517.245 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
- May be involved in cell growth. Probably acts as a terminal oxidase of plasma electron transport from cytosolic NAD(P)H via hydroquinones to acceptors at the cell surface. Hydroquinone oxidase activity alternates with a protein disulfide-thiol interchange/oxidoreductase activity which may control physical membrane displacements associated with vesicle budding or cell enlargement. The activities oscillate with a period length of 22 minutes and play a role in control of the ultradian cellular biological clock
- Specific Function
- oxidoreductase activity
- Gene Name
- ENOX2
- Uniprot ID
- Q16206
- Uniprot Name
- Ecto-NOX disulfide-thiol exchanger 2
- Molecular Weight
- 70081.515 Da
References
- Morre DJ, Chueh PJ, Yagiz K, Balicki A, Kim C, Morre DM: ECTO-NOX target for the anticancer isoflavene phenoxodiol. Oncol Res. 2007;16(7):299-312. [Article]
Drug created at October 21, 2007 22:23 / Updated at August 26, 2024 19:23