INDISULAM

Details

Stereochemistry	ACHIRAL
Molecular Formula	C14H12ClN3O4S2
Molecular Weight	385.846
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NS(=O)(=O)C1=CC=C(C=C1)S(=O)(=O)NC2=C3NC=C(Cl)C3=CC=C2

InChI

InChIKey=SETFNECMODOHTO-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/29660836 | https://www.ncbi.nlm.nih.gov/pubmed/18414469 | https://www.ncbi.nlm.nih.gov/pubmed/12556221 |

Indisulam (also known as E7070) is a sulfonamide derivative patented by Japanese pharmaceutical company Eisai Co. as antitumor agent. Indisulam inhibits cyclin-dependent kinases (CDK), which regulate cell cycle progression and are usually over-expressed in cancerous cells. Inhibition of CDK results in G1/S phase arrest of the cell cycle, and may lead to induction of apoptosis and inhibition of tumor cell proliferation. Preclinical and clinical studies have established the synergy of indisulam with nucleoside analogs as well as topoisomerase inhibitors. These combinations were tolerated with acceptable toxicities, including diarrhea, vomiting, and myelosuppression. In Phase II clinical trials Combination of indisulam with DNA‐damaging agent (idarubicin) and nucleoside analog (cytarabine) in patients with relapsed and refractory AML is effective and largely well tolerated.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Carbonic anhydrase I 62 Target ID: CHEMBL261 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14698154	Inhibitor 8297	31.0 nM [IC50]
Carbonic anhydrase VI 16 Target ID: CHEMBL3025 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17228881	Inhibitor 8297	47.0 nM [Ki]
Carbonic anhydrase II 88 Target ID: CHEMBL205 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14698154	Inhibitor 8297	15.0 nM [IC50]
Carbonic anhydrase IX 35 Target ID: CHEMBL3594 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17228881	Inhibitor 8297	24.0 nM [Ki]

PubMed

Title	Date	PubMed
Mechanisms of action of the novel sulfonamide anticancer agent E7070 on cell cycle progression in human non-small cell lung cancer cells.	2001	11561678
Development and validation of limited sampling strategies for prediction of the systemic exposure to the novel anticancer agent E7070 (N-(3-chloro-7-indolyl)-1,4-benzenedisulphonamide).	2002 Nov	12445024
E7070: a novel synthetic sulfonamide targeting the cell cycle progression for the treatment of cancer.	2002 Nov	12439332
Array-based structure and gene expression relationship study of antitumor sulfonamides including N-[2-[(4-hydroxyphenyl)amino]-3-pyridinyl]-4-methoxybenzenesulfonamide and N-(3-chloro-7-indolyl)-1,4-benzenedisulfonamide.	2002 Oct 24	12383017
An excretion balance and pharmacokinetic study of the novel anticancer agent E7070 in cancer patients.	2002 Sep	12394264
New analogues of the anticancer E7070: synthesis and pharmacology.	2003 Apr	12943191
Indisulam: an anticancer sulfonamide in clinical development.	2003 Feb	12556221
In vitro pharmacokinetic study of the novel anticancer agent E7070: red blood cell and plasma protein binding in human blood.	2003 Jul	12853880
Phase I clinical and pharmacokinetic study of E7070, a novel sulfonamide given as a 5-day continuous infusion repeated every 3 weeks in patients with solid tumours. A study by the EORTC Early Clinical Study Group (ECSG).	2003 May	12736109
Quantitative chemical proteomics for identifying candidate drug targets.	2003 May 1	12720356
Phase I and pharmacokinetic study of E7070, a chloroindolyl-sulfonamide anticancer agent, administered on a weekly schedule to patients with solid tumors.	2003 Nov 1	14613999
Quantitative determination of the novel anticancer drug E7070 (indisulam) and its metabolite (1,4-benzenedisulphonamide) in human plasma, urine and faeces by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry.	2004	15517526
Pharmacokinetic drug-drug interaction of the novel anticancer agent E7070 and acenocoumarol.	2004 Apr	14739663
Carbonic anhydrase inhibitors: E7070, a sulfonamide anticancer agent, potently inhibits cytosolic isozymes I and II, and transmembrane, tumor-associated isozyme IX.	2004 Jan 5	14684331
A phase II clinical and pharmacodynamic study of E7070 in patients with metastatic, recurrent, or refractory squamous cell carcinoma of the head and neck: modulation of retinoblastoma protein phosphorylation by a novel chloroindolyl sulfonamide cell cycle inhibitor.	2004 Jul 15	15269140
Human metabolism of [(14)C]indisulam following i.v. infusion in cancer patients.	2005 Aug	16012791
Phase II study of E7070 in patients with metastatic melanoma.	2005 Jan	15598954
Semi-physiological model describing the hematological toxicity of the anti-cancer agent indisulam.	2005 Jun	15868378
Drugging cell cycle kinases in cancer therapy.	2005 May	15857291
Phase I pharmacokinetic and pharmacogenomic study of E7070 administered once every 21 days.	2005 Oct	16232205
Saturable binding of indisulam to plasma proteins and distribution to human erythrocytes.	2006 Jun	16565173
Carbonic anhydrase inhibitors: cloning, characterization, and inhibition studies of the cytosolic isozyme III with sulfonamides.	2007 Dec 1	17826101
A phase I and pharmacokinetic study of indisulam in combination with carboplatin.	2007 Feb 26	17285128
CYP2C9 and CYP2C19 polymorphic forms are related to increased indisulam exposure and higher risk of severe hematologic toxicity.	2007 May 15	17504998
A dose-escalation study of indisulam in combination with capecitabine (Xeloda) in patients with solid tumours.	2008 Apr 22	18414469
Development of small molecule carbonic anhydrase IX inhibitors.	2008 Jun	18430122
Covariate-based dose individualization of the cytotoxic drug indisulam to reduce the risk of severe myelosuppression.	2009 Feb	19199010
Two-stage model-based clinical trial design to optimize phase I development of novel anticancer agents.	2010 Feb	19198760
Carbonic anhydrase inhibitors: synthesis and inhibition of the human carbonic anhydrase isoforms I, II, VII, IX and XII with benzene sulfonamides incorporating 4,5,6,7-tetrabromophthalimide moiety.	2013 Oct 1	23965175

Patents

Sample Use Guides

In Vivo Use Guide

400 mg/ m^2 on days 1 and 8 of a 28-day cycle

Route of Administration: Intravenous

Name

Type

Language

INDISULAM

Official Name

English

Indisulam [WHO-DD]

Common Name

English

1,4-Benzenedisulfonamide, N-(3-chloro-1H-indol-7-yl)

Systematic Name

English

INDISULAM [MI]

Common Name

English

N-(3-CHLORO-1H-INDOL-7-YL)BENZENE-1,4-DISULFONAMIDE

Systematic Name

English

E7070

Code

English

INDISULAM [USAN]

Common Name

English

E-7070

Code

English

indisulam [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29577