This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Name
Indisulam
Accession Number
DB06370
Type
Small Molecule
Groups
Investigational
Description
Not Available
Structure
Thumb
Synonyms
Not Available
External IDs
E-7070 / E7070
Categories
UNII
WJ98J3NM90
CAS number
165668-41-7
Weight
Average: 385.846
Monoisotopic: 384.995774974
Chemical Formula
C14H12ClN3O4S2
InChI Key
SETFNECMODOHTO-UHFFFAOYSA-N
InChI
InChI=1S/C14H12ClN3O4S2/c15-12-8-17-14-11(12)2-1-3-13(14)18-24(21,22)10-6-4-9(5-7-10)23(16,19)20/h1-8,17-18H,(H2,16,19,20)
IUPAC Name
N1-(3-chloro-1H-indol-7-yl)benzene-1,4-disulfonamide
SMILES
NS(=O)(=O)C1=CC=C(C=C1)S(=O)(=O)NC1=CC=CC2=C1NC=C2Cl

Pharmacology

Indication

Investigated for use/treatment in lung cancer.

Pharmacodynamics
Not Available
Mechanism of action

E7070 is a novel sulfonamide antitumoragent that exhibits potent antitumoractivity in vitro and in vivo. This compound affects cell cycleprogression in human tumor cells

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
DrugInteraction
AbirateroneThe metabolism of Indisulam can be decreased when combined with Abiraterone.
Acetyl sulfisoxazoleThe metabolism of Indisulam can be decreased when combined with Acetyl sulfisoxazole.
AlbendazoleThe metabolism of Albendazole can be decreased when combined with Indisulam.
AlclometasoneThe metabolism of Alclometasone can be decreased when combined with Indisulam.
AlfuzosinThe metabolism of Alfuzosin can be decreased when combined with Indisulam.
AlprazolamThe metabolism of Alprazolam can be decreased when combined with Indisulam.
AmcinonideThe metabolism of Amcinonide can be decreased when combined with Indisulam.
AmitriptylineThe metabolism of Amitriptyline can be decreased when combined with Indisulam.
AmlodipineThe metabolism of Amlodipine can be decreased when combined with Indisulam.
ApalutamideThe serum concentration of Indisulam can be decreased when it is combined with Apalutamide.
Food Interactions
Not Available

References

General References
  1. Zandvliet AS, Copalu W, Schellens JH, Beijnen JH, Huitema AD: Saturable binding of indisulam to plasma proteins and distribution to human erythrocytes. Drug Metab Dispos. 2006 Jun;34(6):1041-6. Epub 2006 Mar 24. [PubMed:16565173]
  2. Fukuoka K, Usuda J, Iwamoto Y, Fukumoto H, Nakamura T, Yoneda T, Narita N, Saijo N, Nishio K: Mechanisms of action of the novel sulfonamide anticancer agent E7070 on cell cycle progression in human non-small cell lung cancer cells. Invest New Drugs. 2001;19(3):219-27. [PubMed:11561678]
  3. van den Bongard HJ, Sparidans RW, Critchley DJ, Beijnen JH, Schellens JH: Pharmacokinetic drug-drug interaction of the novel anticancer agent E7070 and acenocoumarol. Invest New Drugs. 2004 Apr;22(2):151-8. [PubMed:14739663]
External Links
PubChem Compound
216468
ChemSpider
187608
BindingDB
10890
ChEMBL
CHEMBL77517

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentUnspecified Adult Solid Tumor, Protocol Specific2
1, 2TerminatedTreatmentMalignant Neoplasm of Stomach1
2CompletedTreatmentColorectal Cancer (CRC)1
2CompletedTreatmentColorectal Cancers1
2CompletedTreatmentLeukemias1
2CompletedTreatmentMelanoma (Skin)1
2CompletedTreatmentMetastases / Neoplasms, Breast1
2CompletedTreatmentNeoplasms, Kidney / Renal Cell Adenocarcinoma1
2TerminatedDiagnosticMetastatic Breast Cancer (MBC)1

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 Solubility0.0213 mg/mLALOGPS
logP2.21ALOGPS
logP1.77ChemAxon
logS-4.3ALOGPS
pKa (Strongest Acidic)6.85ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area122.12 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity90.94 m3·mol-1ChemAxon
Polarizability35.23 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9878
Blood Brain Barrier+0.7882
Caco-2 permeable-0.532
P-glycoprotein substrateNon-substrate0.7884
P-glycoprotein inhibitor INon-inhibitor0.9244
P-glycoprotein inhibitor IINon-inhibitor0.96
Renal organic cation transporterNon-inhibitor0.8899
CYP450 2C9 substrateNon-substrate0.8342
CYP450 2D6 substrateNon-substrate0.8209
CYP450 3A4 substrateNon-substrate0.6469
CYP450 1A2 substrateInhibitor0.5119
CYP450 2C9 inhibitorInhibitor0.5313
CYP450 2D6 inhibitorNon-inhibitor0.8112
CYP450 2C19 inhibitorInhibitor0.588
CYP450 3A4 inhibitorNon-inhibitor0.7418
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5339
Ames testNon AMES toxic0.7897
CarcinogenicityNon-carcinogens0.7361
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.3920 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9392
hERG inhibition (predictor II)Non-inhibitor0.8184
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 GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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 sulfanilides. These are organic aromatic compounds containing a sulfanilide moiety, with the general structure RS(=O)(=O)NC1=CC=CC=C1.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Sulfanilides
Direct Parent
Sulfanilides
Alternative Parents
Benzenesulfonamides / Indoles / Benzenesulfonyl compounds / Substituted pyrroles / Organosulfonamides / Aryl chlorides / Heteroaromatic compounds / Aminosulfonyl compounds / Azacyclic compounds / Organopnictogen compounds
show 4 more
Substituents
Benzenesulfonamide / Sulfanilide / Indole / Benzenesulfonyl group / Indole or derivatives / Aryl chloride / Aryl halide / Substituted pyrrole / Organosulfonic acid amide / Heteroaromatic compound
show 17 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Zandvliet AS, Siegel-Lakhai WS, Beijnen JH, Copalu W, Etienne-Grimaldi MC, Milano G, Schellens JH, Huitema AD: PK/PD model of indisulam and capecitabine: interaction causes excessive myelosuppression. Clin Pharmacol Ther. 2008 Jun;83(6):829-39. Epub 2007 Sep 12. [PubMed:17851564]
  2. Yamada Y, Yamamoto N, Shimoyama T, Horiike A, Fujisaka Y, Takayama K, Sakamoto T, Nishioka Y, Yasuda S, Tamura T: Phase I pharmacokinetic and pharmacogenomic study of E7070 administered once every 21 days. Cancer Sci. 2005 Oct;96(10):721-8. [PubMed:16232205]
  3. Zandvliet AS, Huitema AD, Copalu W, Yamada Y, Tamura T, Beijnen JH, Schellens JH: CYP2C9 and CYP2C19 polymorphic forms are related to increased indisulam exposure and higher risk of severe hematologic toxicity. Clin Cancer Res. 2007 May 15;13(10):2970-6. [PubMed:17504998]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. van den Bongard HJ, Sparidans RW, Critchley DJ, Beijnen JH, Schellens JH: Pharmacokinetic drug-drug interaction of the novel anticancer agent E7070 and acenocoumarol. Invest New Drugs. 2004 Apr;22(2):151-8. [PubMed:14739663]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
Molecular Weight
56848.42 Da
References
  1. van den Bongard HJ, Sparidans RW, Critchley DJ, Beijnen JH, Schellens JH: Pharmacokinetic drug-drug interaction of the novel anticancer agent E7070 and acenocoumarol. Invest New Drugs. 2004 Apr;22(2):151-8. [PubMed:14739663]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. van den Bongard HJ, Sparidans RW, Critchley DJ, Beijnen JH, Schellens JH: Pharmacokinetic drug-drug interaction of the novel anticancer agent E7070 and acenocoumarol. Invest New Drugs. 2004 Apr;22(2):151-8. [PubMed:14739663]

Drug created on March 19, 2008 10:27 / Updated on September 25, 2018 03:16