Explore a selection of our essential drug information below, or:
Identification
- Generic Name
- Edotecarin
- DrugBank Accession Number
- DB04882
- Background
Edotecarin is a novel, non-camptothecin, DNA topoisomerase I inhibitor. It is member of the class of compounds called indolocarbazoles.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
Structure for Edotecarin (DB04882)
- Weight
- Average: 608.56
Monoisotopic: 608.175457738 - Chemical Formula
- C29H28N4O11
- Synonyms
- E'dotecarine
- Edotecarin
- Edotecarina
- Edotecarinum
- External IDs
- J 107088
- J-107088
- PF-804950
- PHA-782615
Pharmacology
- Indication
Clinical studies with edotecarin have shown activity in subjects with colorectal cancer, esophageal cancer and other solid tumors.
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Edotecarin, formerly J-107088 is a novel, non-camptothecin, DNA topoisomerase-1 inhibitor. It is part of the class of compounds called indolocarbazoles. It is a novel inhibitor of topoisomerase I that induces single-strand DNA cleavage more effectively than NB-506 or camptothecin (CPT) and at different DNA sequences. The DNA-topoisomerase I complexes induced by edotecarin are more stable than those occurring after exposure to CPT or NB-506. The antitumor activity of edotecarin is less cell cycle dependent than other topoisomerase I inhibitors. Being an indolocarbazole, it is structurally related to staurosporine but does not possess protein kinase inhibitory properties. The antitumor activity of edotecarin has been tested in vitro and in vivo, and inhibition of tumor growth has been observed in breast, cervix, pharynx, lung, prostate, colon, gastric, and hepatic cancer models. Edotecarin is effective on cells that have acquired resistance related to P-glycoprotein. In vitro synergy has been demonstrated when edotecarin was tested in combination with cisplatin, 5-fluorouracil, etoposide, paclitaxel, doxorubicin, vincristine, CPT, and gemcitabine.
- Mechanism of action
Edotecarin inhibits the enzyme topoisomerase I through stabilization of the DNA-enzyme complex and enhanced single-strand DNA cleavage, resulting in inhibition of DNA replication and decreased tumor cell proliferation.
Target Actions Organism ADNA topoisomerase 1 inhibitorHumans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
Edotecarin does not form active metabolites and is not a substrate for in vitro P450-mediated metabolism.
- Route of elimination
Not Available
- Half-life
20 to 25 hours
- Clearance
Not Available
- Adverse Effects
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Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- Not Available
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as indolocarbazoles. These are polycyclic aromatic compounds containing an indole fused to a carbazole.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Indoles and derivatives
- Sub Class
- Carbazoles
- Direct Parent
- Indolocarbazoles
- Alternative Parents
- Pyrrolo[2,3-a]carbazoles / Pyrroloindoles / Glycosylamines / Phthalimides / Hydroxyindoles / N-alkylindoles / Indoles / 1-hydroxy-2-unsubstituted benzenoids / Monosaccharides / Substituted pyrroles show 12 more
- Substituents
- 1-hydroxy-2-unsubstituted benzenoid / Alcohol / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Carboxylic acid derivative / Carboxylic acid hydrazide / Glycosyl compound / Heteroaromatic compound / Hydrocarbon derivative show 25 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 1V8X590XDP
- CAS number
- 174402-32-5
- InChI Key
- QMVPQBFHUJZJCS-NTKFZFFISA-N
- InChI
- InChI=1S/C29H28N4O11/c34-7-10(8-35)31-33-27(42)20-18-13-3-1-11(37)5-15(13)30-22(18)23-19(21(20)28(33)43)14-4-2-12(38)6-16(14)32(23)29-26(41)25(40)24(39)17(9-36)44-29/h1-6,10,17,24-26,29-31,34-41H,7-9H2/t17-,24-,25+,26-,29-/m1/s1
- IUPAC Name
- 13-[(1,3-dihydroxypropan-2-yl)amino]-6,20-dihydroxy-3-[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]-3,13,23-triazahexacyclo[14.7.0.0²,¹⁰.0⁴,⁹.0¹¹,¹⁵.0¹⁷,²²]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione
- SMILES
- OCC(CO)NN1C(=O)C2=C3C(NC4=C3C=CC(O)=C4)=C3N([C@@H]4O[C@H](CO)[C@@H](O)[C@H](O)[C@H]4O)C4=C(C=CC(O)=C4)C3=C2C1=O
References
- General References
- Saif MW, Diasio RB: Edotecarin: a novel topoisomerase I inhibitor. Clin Colorectal Cancer. 2005 May;5(1):27-36. [Article]
- Yamada Y, Tamura T, Yamamoto N, Shimoyama T, Ueda Y, Murakami H, Kusaba H, Kamiya Y, Saka H, Tanigawara Y, McGovren JP, Natsumeda Y: Phase I and pharmacokinetic study of edotecarin, a novel topoisomerase I inhibitor, administered once every 3 weeks in patients with solid tumors. Cancer Chemother Pharmacol. 2006 Aug;58(2):173-82. Epub 2005 Nov 25. [Article]
- Vrdoljak E, Boban M, Saratlija-Novakovic Z, Jovic J: Long-lasting partial regression of glioblastoma multiforme achieved by edotecarin: case report. Croat Med J. 2006 Apr;47(2):305-9. [Article]
- Ciomei M, Croci V, Ciavolella A, Ballinari D, Pesenti E: Antitumor efficacy of edotecarin as a single agent and in combination with chemotherapy agents in a xenograft model. Clin Cancer Res. 2006 May 1;12(9):2856-61. [Article]
- Hurwitz HI, Cohen RB, McGovren JP, Hirawat S, Petros WP, Natsumeda Y, Yoshinari T: A phase I study of the safety and pharmacokinetics of edotecarin (J-107088), a novel topoisomerase I inhibitor, in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2007 Jan;59(1):139-47. Epub 2006 Jul 4. [Article]
- Ciomei M, Croci V, Stellari F, Amboldi N, Giavarini R, Pesenti E: Antitumor activity of edotecarin in breast carcinoma models. Cancer Chemother Pharmacol. 2007 Jul;60(2):229-35. Epub 2006 Nov 7. [Article]
- External Links
- KEGG Drug
- D03954
- PubChem Compound
- 9808998
- PubChem Substance
- 175426885
- ChemSpider
- 7984757
- BindingDB
- 50086570
- ChEMBL
- CHEMBL435191
- ZINC
- ZINC000003946372
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample data3 Completed Treatment High Grade Glioma: Glioblastoma (GBM) 1 somestatus stop reason just information to hide 2 Completed Treatment Breast Cancer 1 somestatus stop reason just information to hide 2 Completed Treatment Breast Neoplasms / Metastatic Cancer 1 somestatus stop reason just information to hide 2 Completed Treatment Neoplasm of Stomach 1 somestatus stop reason just information to hide 1 Completed Treatment Esophageal Cancer / Gastric Cancer / Unspecified Adult Solid Tumor, Protocol Specific 1 somestatus stop reason just information to hide
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
Property Value Source Water Solubility 1.58 mg/mL ALOGPS logP -0.11 ALOGPS logP -1.3 Chemaxon logS -2.6 ALOGPS pKa (Strongest Acidic) 8.82 Chemaxon pKa (Strongest Basic) 2.44 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 12 Chemaxon Hydrogen Donor Count 10 Chemaxon Polar Surface Area 241.2 Å2 Chemaxon Rotatable Bond Count 6 Chemaxon Refractivity 161.73 m3·mol-1 Chemaxon Polarizability 61.93 Å3 Chemaxon Number of Rings 7 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.8545 Blood Brain Barrier - 0.5252 Caco-2 permeable - 0.7519 P-glycoprotein substrate Substrate 0.5195 P-glycoprotein inhibitor I Non-inhibitor 0.9127 P-glycoprotein inhibitor II Non-inhibitor 0.9314 Renal organic cation transporter Non-inhibitor 0.9176 CYP450 2C9 substrate Non-substrate 0.8461 CYP450 2D6 substrate Non-substrate 0.8426 CYP450 3A4 substrate Substrate 0.5352 CYP450 1A2 substrate Non-inhibitor 0.8865 CYP450 2C9 inhibitor Non-inhibitor 0.7748 CYP450 2D6 inhibitor Non-inhibitor 0.873 CYP450 2C19 inhibitor Non-inhibitor 0.893 CYP450 3A4 inhibitor Non-inhibitor 0.8458 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7723 Ames test Non AMES toxic 0.5481 Carcinogenicity Non-carcinogens 0.7828 Biodegradation Not ready biodegradable 0.9945 Rat acute toxicity 2.2674 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9487 hERG inhibition (predictor II) Non-inhibitor 0.5871
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 237.16785 predictedDeepCCS 1.0 (2019) [M+H]+ 238.83965 predictedDeepCCS 1.0 (2019) [M+Na]+ 244.97787 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(3'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 5'-OH DNA strand. The free DNA strand then rotates around the intact phosphodiester bond on the opposing strand, thus removing DNA supercoils. Finally, in the religation step, the DNA 5'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone (By similarity). Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells. Involved in the circadian transcription of the core circadian clock component BMAL1 by altering the chromatin structure around the ROR response elements (ROREs) on the BMAL1 promoter
- Specific Function
- ATP binding
- Gene Name
- TOP1
- Uniprot ID
- P11387
- Uniprot Name
- DNA topoisomerase 1
- Molecular Weight
- 90725.19 Da
References
- Carvajal RD, Ilson DH, Noy A: Possible role of edotecarin, a novel topoisomerase I inhibitor, in therapy-related myelodysplastic syndrome. Leuk Lymphoma. 2007 Jan;48(1):192-4. [Article]
- Saif MW, Diasio RB: Edotecarin: a novel topoisomerase I inhibitor. Clin Colorectal Cancer. 2005 May;5(1):27-36. [Article]
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
Drug created at October 21, 2007 11:15 / Updated at August 26, 2024 19:23