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

Molecular Formula	C14H12ClN3O4S2
Molecular Weight	385.846
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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
Anticancer agent E7070 inhibits amino acid and uracil transport in fission yeast.	2001 Dec	11723232
Phase I and pharmacokinetic study of E7070, a novel sulfonamide, given at a daily times five schedule in patients with solid tumors. A study by the EORTC-early clinical studies group (ECSG).	2001 Sep	11697842
Population pharmacokinetics of the novel anticancer agent E7070 during four phase I studies: model building and validation.	2002 Oct 1	12351604
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
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
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
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
Targeting tumor-associated carbonic anhydrase IX in cancer therapy.	2006 Nov	16996620
A semi-physiological population pharmacokinetic model describing the non-linear disposition of indisulam.	2006 Oct	16946998
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
A randomized phase II pharmacokinetic and pharmacodynamic study of indisulam as second-line therapy in patients with advanced non-small cell lung cancer.	2007 Mar 15	17363538
CYP2C9 and CYP2C19 polymorphic forms are related to increased indisulam exposure and higher risk of severe hematologic toxicity.	2007 May 15	17504998
Clinical complete long-term remission of a patient with metastatic malignant melanoma under therapy with indisulam (E7070).	2007 Oct	17885589
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
PK/PD model of indisulam and capecitabine: interaction causes excessive myelosuppression.	2008 Jun	17851564
Population pharmacokinetic and pharmacodynamic analysis to support treatment optimization of combination chemotherapy with indisulam and carboplatin.	2008 Oct	18637887
Covariate-based dose individualization of the cytotoxic drug indisulam to reduce the risk of severe myelosuppression.	2009 Feb	19199010
Self-associated indisulam in phospholipid-based nanomicelles: a potential nanomedicine for cancer.	2009 Jun	19071064
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

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:40:43 GMT 2023` Edited by `admin` on `Fri Dec 15 15:40:43 GMT 2023`
Record UNII	WJ98J3NM90
Record Status	`Validated (UNII)`
Record Version

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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