Identification
- Generic Name
- Canfosfamide
- DrugBank Accession Number
- DB04972
- Background
Canfosfamide is an active agent in chemotherapy-resistant ovarian cancer.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
Structure for Canfosfamide (DB04972)
- Weight
- Average: 787.46
Monoisotopic: 785.0987615 - Chemical Formula
- C26H40Cl4N5O10PS
- Synonyms
- Canfosfamide
Pharmacology
- Indication
Intended for the treatment of various forms of cancer.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Contraindications & Blackbox Warnings
Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.- Pharmacodynamics
Not Available
- Mechanism of action
S-transferase P1-1 (GST P1-1) is an enzyme overexpressed in many human cancer cells. High levels of GST P1-1 are associated with a poor prognosis and resistance to certain chemotherapeutics. The activation of canfosfamide occurs when GST P1-1 splits canfosfamide into two active fragments: a glutathione analog fragment and an active cytotoxic fragment. The cytotoxic fragment reacts with important cell components, including RNA, DNA and proteins, leading to cell death. The glutathione analog fragment of canfosfamide may remain bound to GST P1-1, which may limit the ability of GST P1-1 to inactivate other cancer drugs.
Target Actions Organism UGlutathione S-transferase P Not Available Humans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
18 min
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Canfosfamide-related toxicities included grade 1-2 nausea, vomiting, fatigue, transient microscopic hematuria, and anemia.
- 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
Products
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Ingredient UNII CAS InChI Key Canfosfamide hydrochloride 1LI341K7NQ 439943-59-6 NECZZOFFLFZNHL-XVGZVFJZSA-N - International/Other Brands
- Telcyta
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as oligopeptides. These are organic compounds containing a sequence of between three and ten alpha-amino acids joined by peptide bonds.
- Kingdom
- Organic compounds
- Super Class
- Organic acids and derivatives
- Class
- Carboxylic acids and derivatives
- Sub Class
- Amino acids, peptides, and analogues
- Direct Parent
- Oligopeptides
- Alternative Parents
- Gamma-glutamyl peptides / Glutamine and derivatives / N-acyl-alpha amino acids / Alpha amino acid amides / L-alpha-amino acids / Nitrogen mustard compounds / Phosphoric monoester diamides / Phosphate esters / Benzene and substituted derivatives / N-acyl amines show 12 more
- Substituents
- Alkyl chloride / Alkyl halide / Alpha-amino acid / Alpha-amino acid amide / Alpha-amino acid or derivatives / Alpha-oligopeptide / Amine / Amino acid / Amino acid or derivatives / Aromatic homomonocyclic compound show 35 more
- Molecular Framework
- Aromatic homomonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 1RS284BFUI
- CAS number
- 158382-37-7
- InChI Key
- OJLHWPALWODJPQ-QNWVGRARSA-N
- InChI
- InChI=1S/C26H40Cl4N5O10PS/c27-8-12-34(13-9-28)46(42,35(14-10-29)15-11-30)45-16-17-47(43,44)18-21(32-22(36)7-6-20(31)25(38)39)24(37)33-23(26(40)41)19-4-2-1-3-5-19/h1-5,20-21,23H,6-18,31H2,(H,32,36)(H,33,37)(H,38,39)(H,40,41)/t20-,21-,23+/m0/s1
- IUPAC Name
- (2S)-2-amino-4-{[(1R)-2-[2-({bis[bis(2-chloroethyl)amino]phosphoryl}oxy)ethanesulfonyl]-1-{[(R)-carboxy(phenyl)methyl]carbamoyl}ethyl]carbamoyl}butanoic acid
- SMILES
- N[C@@H](CCC(=O)N[C@@H](CS(=O)(=O)CCOP(=O)(N(CCCl)CCCl)N(CCCl)CCCl)C(=O)N[C@@H](C(O)=O)C1=CC=CC=C1)C(O)=O
References
- General References
- Rosen LS, Brown J, Laxa B, Boulos L, Reiswig L, Henner WD, Lum RT, Schow SR, Maack CA, Keck JG, Mascavage JC, Dombroski JA, Gomez RF, Brown GL: Phase I study of TLK286 (glutathione S-transferase P1-1 activated glutathione analogue) in advanced refractory solid malignancies. Clin Cancer Res. 2003 May;9(5):1628-38. [Article]
- Rosen LS, Laxa B, Boulos L, Wiggins L, Keck JG, Jameson AJ, Parra R, Patel K, Brown GL: Phase 1 study of TLK286 (Telcyta) administered weekly in advanced malignancies. Clin Cancer Res. 2004 Jun 1;10(11):3689-98. [Article]
- Kavanagh JJ, Gershenson DM, Choi H, Lewis L, Patel K, Brown GL, Garcia A, Spriggs DR: Multi-institutional phase 2 study of TLK286 (TELCYTA, a glutathione S-transferase P1-1 activated glutathione analog prodrug) in patients with platinum and paclitaxel refractory or resistant ovarian cancer. Int J Gynecol Cancer. 2005 Jul-Aug;15(4):593-600. [Article]
- External Links
- PubChem Compound
- 5312109
- PubChem Substance
- 175426923
- ChemSpider
- 4471543
- ChEBI
- 135883
- ChEMBL
- CHEMBL2111086
- ZINC
- ZINC000085537051
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 3 Completed Treatment Non-Small Cell Lung Carcinoma 1 3 Completed Treatment Ovarian Neoplasms 2 3 Terminated Treatment Ovarian Neoplasms 1 2 Completed Treatment B-Cell Lymphoma / Mantle Cell Lymphoma (MCL) / Multiple Myeloma (MM) 1 2 Completed Treatment Breast Neoplasms 1 2 Completed Treatment Fallopian Tube Cancer / Ovarian Cancer / Primary Peritoneal Cancer 1 2 Completed Treatment Lung Cancer 1 2 Completed Treatment Non-Small Cell Lung Carcinoma 1 2 Completed Treatment Ovarian Neoplasms 1 1, 2 Completed Treatment Non-Small Cell Lung Cancer (NSCLC) 1
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 0.0385 mg/mL ALOGPS logP -1 ALOGPS logP -2.9 Chemaxon logS -4.3 ALOGPS pKa (Strongest Acidic) 1.37 Chemaxon pKa (Strongest Basic) 9.26 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 10 Chemaxon Hydrogen Donor Count 5 Chemaxon Polar Surface Area 225.74 Å2 Chemaxon Rotatable Bond Count 25 Chemaxon Refractivity 175.76 m3·mol-1 Chemaxon Polarizability 74.17 Å3 Chemaxon Number of Rings 1 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.8011 Blood Brain Barrier - 0.5714 Caco-2 permeable - 0.6575 P-glycoprotein substrate Substrate 0.5368 P-glycoprotein inhibitor I Non-inhibitor 0.7168 P-glycoprotein inhibitor II Non-inhibitor 0.988 Renal organic cation transporter Non-inhibitor 0.9319 CYP450 2C9 substrate Non-substrate 0.7047 CYP450 2D6 substrate Non-substrate 0.8022 CYP450 3A4 substrate Non-substrate 0.6248 CYP450 1A2 substrate Non-inhibitor 0.8303 CYP450 2C9 inhibitor Non-inhibitor 0.7946 CYP450 2D6 inhibitor Non-inhibitor 0.8697 CYP450 2C19 inhibitor Non-inhibitor 0.751 CYP450 3A4 inhibitor Non-inhibitor 0.6174 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9628 Ames test Non AMES toxic 0.5106 Carcinogenicity Non-carcinogens 0.7611 Biodegradation Ready biodegradable 0.6223 Rat acute toxicity 2.5940 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.869 hERG inhibition (predictor II) Non-inhibitor 0.7566
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- S-nitrosoglutathione binding
- Specific Function
- Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Regulates negatively CDK5 activity via p25/p35 translocation to prevent neurodegeneration.
- Gene Name
- GSTP1
- Uniprot ID
- P09211
- Uniprot Name
- Glutathione S-transferase P
- Molecular Weight
- 23355.625 Da
References
- Kavanagh JJ, Gershenson DM, Choi H, Lewis L, Patel K, Brown GL, Garcia A, Spriggs DR: Multi-institutional phase 2 study of TLK286 (TELCYTA, a glutathione S-transferase P1-1 activated glutathione analog prodrug) in patients with platinum and paclitaxel refractory or resistant ovarian cancer. Int J Gynecol Cancer. 2005 Jul-Aug;15(4):593-600. [Article]
- Rosen LS, Brown J, Laxa B, Boulos L, Reiswig L, Henner WD, Lum RT, Schow SR, Maack CA, Keck JG, Mascavage JC, Dombroski JA, Gomez RF, Brown GL: Phase I study of TLK286 (glutathione S-transferase P1-1 activated glutathione analogue) in advanced refractory solid malignancies. Clin Cancer Res. 2003 May;9(5):1628-38. [Article]
Drug created at October 21, 2007 22:23 / Updated at February 03, 2023 08:17