Identification

Name
Irosustat
Accession Number
DB02292  (EXPT00273, DB12437)
Type
Small Molecule
Groups
Investigational
Description

Irosustat has been investigated for the treatment of Metastatic Breast Cancer and Locally Advanced Breast Cancer.

Structure
Thumb
Synonyms
  • 6-Oxo-8,9,10,11-Tetrahydro-7h-Cyclohepta[C][1]Benzopyran-3-O-Sulfamate
External IDs
667 COUMATE / 667-COUMATE / BN 83495 / BN-83495 / BN83495 / STX 64 / STX-64 / STX64
Categories
Not Available
UNII
366037O6O7
CAS number
288628-05-7
Weight
Average: 309.338
Monoisotopic: 309.067093285
Chemical Formula
C14H15NO5S
InChI Key
DSLPMJSGSBLWRE-UHFFFAOYSA-N
InChI
InChI=1S/C14H15NO5S/c15-21(17,18)20-9-6-7-11-10-4-2-1-3-5-12(10)14(16)19-13(11)8-9/h6-8H,1-5H2,(H2,15,17,18)
IUPAC Name
6-oxo-6H,7H,8H,9H,10H,11H-cyclohepta[c]chromen-3-yl sulfamate
SMILES
NS(=O)(=O)OC1=CC=C2C3=C(CCCCC3)C(=O)OC2=C1

Pharmacology

Indication
Not Available
Pharmacodynamics
Not Available
Mechanism of action
TargetActionsOrganism
UCarbonic anhydrase 2Not AvailableHuman
USteryl-sulfatase
inhibitor
Human
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
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
Not Available
External Links
PubChem Compound
5287541
PubChem Substance
46507132
ChemSpider
4449897
BindingDB
13058
ChEMBL
CHEMBL286738
HET
667
Wikipedia
Irosustat
PDB Entries
1ttm

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentCancer, Breast1
1CompletedTreatmentProstate Cancer1
2CompletedTreatmentEndometrial Cancers1
2CompletedTreatmentLocally Advanced Breast Cancer (LABC) / Metastatic Breast Cancer (MBC)1
2TerminatedBasic ScienceCancer, Breast1
2TerminatedTreatmentEndometrial Cancers1
2TerminatedTreatmentNeoplasms, Breast1

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
PropertyValueSource
Water Solubility0.0967 mg/mLALOGPS
logP2.76ALOGPS
logP1.99ChemAxon
logS-3.5ALOGPS
pKa (Strongest Acidic)10.65ChemAxon
pKa (Strongest Basic)-6ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area95.69 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity75.7 m3·mol-1ChemAxon
Polarizability30.67 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9963
Blood Brain Barrier+0.953
Caco-2 permeable-0.6178
P-glycoprotein substrateNon-substrate0.721
P-glycoprotein inhibitor INon-inhibitor0.7208
P-glycoprotein inhibitor IINon-inhibitor0.9485
Renal organic cation transporterNon-inhibitor0.865
CYP450 2C9 substrateNon-substrate0.8853
CYP450 2D6 substrateNon-substrate0.81
CYP450 3A4 substrateNon-substrate0.5582
CYP450 1A2 substrateNon-inhibitor0.5336
CYP450 2C9 inhibitorNon-inhibitor0.6732
CYP450 2D6 inhibitorNon-inhibitor0.8703
CYP450 2C19 inhibitorNon-inhibitor0.5966
CYP450 3A4 inhibitorNon-inhibitor0.8664
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8239
Ames testNon AMES toxic0.5347
CarcinogenicityNon-carcinogens0.6975
BiodegradationNot ready biodegradable0.8294
Rat acute toxicity2.4709 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7388
hERG inhibition (predictor II)Non-inhibitor0.6542
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as cycloheptapyrans. These are organic heterocyclic compounds containing a cycloheptane derivative fused to a pyran. Pyran a six-membered heterocyclic, non-aromatic ring, made up of five carbon atoms and one oxygen atom and containing two double bonds.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Cycloheptapyrans
Sub Class
Not Available
Direct Parent
Cycloheptapyrans
Alternative Parents
Coumarins and derivatives / 1-benzopyrans / Pyranones and derivatives / Benzenoids / Organic sulfuric acids and derivatives / Heteroaromatic compounds / Lactones / Oxacyclic compounds / Organooxygen compounds / Organic oxides
show 2 more
Substituents
Coumarin / Cycloheptapyran / Benzopyran / 1-benzopyran / Pyranone / Pyran / Benzenoid / Organic sulfuric acid or derivatives / Heteroaromatic compound / Lactone
show 7 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Details
1. Carbonic anhydrase 2
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Zinc ion binding
Specific Function
Essential for bone resorption and osteoclast differentiation (By similarity). Reversible hydration of carbon dioxide. Can hydrate cyanamide to urea. Involved in the regulation of fluid secretion in...
Gene Name
CA2
Uniprot ID
P00918
Uniprot Name
Carbonic anhydrase 2
Molecular Weight
29245.895 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]
Details
2. Steryl-sulfatase
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sulfuric ester hydrolase activity
Specific Function
Conversion of sulfated steroid precursors to estrogens during pregnancy.
Gene Name
STS
Uniprot ID
P08842
Uniprot Name
Steryl-sulfatase
Molecular Weight
65491.72 Da
References
  1. Purohit A, Woo LW, Potter BV, Reed MJ: In vivo inhibition of estrone sulfatase activity and growth of nitrosomethylurea-induced mammary tumors by 667 COUMATE. Cancer Res. 2000 Jul 1;60(13):3394-6. [PubMed:10910045]

Drug created on June 13, 2005 07:24 / Updated on October 01, 2018 13:17