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
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
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
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
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
Phase II study of E7070 in patients with metastatic melanoma.	2005 Jan	15598954
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
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

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