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
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)
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.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL261 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14698154 |
31.0 nM [IC50] | ||
Target ID: CHEMBL3025 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17228881 |
47.0 nM [Ki] | ||
Target ID: CHEMBL205 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14698154 |
15.0 nM [IC50] | ||
Target ID: CHEMBL3594 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17228881 |
24.0 nM [Ki] |
PubMed
Title | Date | PubMed |
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Mechanisms of action of the novel sulfonamide anticancer agent E7070 on cell cycle progression in human non-small cell lung cancer cells. | 2001 |
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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 |
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E7070: a novel synthetic sulfonamide targeting the cell cycle progression for the treatment of cancer. | 2002 Nov |
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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 |
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An excretion balance and pharmacokinetic study of the novel anticancer agent E7070 in cancer patients. | 2002 Sep |
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New analogues of the anticancer E7070: synthesis and pharmacology. | 2003 Apr |
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Indisulam: an anticancer sulfonamide in clinical development. | 2003 Feb |
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In vitro pharmacokinetic study of the novel anticancer agent E7070: red blood cell and plasma protein binding in human blood. | 2003 Jul |
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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 |
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Quantitative chemical proteomics for identifying candidate drug targets. | 2003 May 1 |
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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 |
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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 |
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Pharmacokinetic drug-drug interaction of the novel anticancer agent E7070 and acenocoumarol. | 2004 Apr |
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Carbonic anhydrase inhibitors: E7070, a sulfonamide anticancer agent, potently inhibits cytosolic isozymes I and II, and transmembrane, tumor-associated isozyme IX. | 2004 Jan 5 |
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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 |
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Human metabolism of [(14)C]indisulam following i.v. infusion in cancer patients. | 2005 Aug |
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Phase II study of E7070 in patients with metastatic melanoma. | 2005 Jan |
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Semi-physiological model describing the hematological toxicity of the anti-cancer agent indisulam. | 2005 Jun |
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Drugging cell cycle kinases in cancer therapy. | 2005 May |
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Phase I pharmacokinetic and pharmacogenomic study of E7070 administered once every 21 days. | 2005 Oct |
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Saturable binding of indisulam to plasma proteins and distribution to human erythrocytes. | 2006 Jun |
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Carbonic anhydrase inhibitors: cloning, characterization, and inhibition studies of the cytosolic isozyme III with sulfonamides. | 2007 Dec 1 |
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A phase I and pharmacokinetic study of indisulam in combination with carboplatin. | 2007 Feb 26 |
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CYP2C9 and CYP2C19 polymorphic forms are related to increased indisulam exposure and higher risk of severe hematologic toxicity. | 2007 May 15 |
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A dose-escalation study of indisulam in combination with capecitabine (Xeloda) in patients with solid tumours. | 2008 Apr 22 |
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Development of small molecule carbonic anhydrase IX inhibitors. | 2008 Jun |
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Covariate-based dose individualization of the cytotoxic drug indisulam to reduce the risk of severe myelosuppression. | 2009 Feb |
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Two-stage model-based clinical trial design to optimize phase I development of novel anticancer agents. | 2010 Feb |
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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 |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/29660836
400 mg/ m^2 on days 1 and 8 of a 28-day cycle
Route of Administration:
Intravenous
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C29577
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C2185
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C25797
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145431
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100000144620
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CHEMBL77517
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E7070
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8199
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m6256
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165668-41-7
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DB06370
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RR-50
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ACTIVE MOIETY