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Identification
NameCanfosfamide
Accession NumberDB04972
TypeSmall Molecule
GroupsInvestigational
Description

Canfosfamide is an active agent in chemotherapy-resistant ovarian cancer.

Structure
Thumb
SynonymsNot Available
External Identifiers
  • TER 286
  • TLK 286
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
TelcytaNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Canfosfamide hydrochloride
439943-59-6
Thumb
  • InChI Key: NECZZOFFLFZNHL-XVGZVFJZSA-N
  • Monoisotopic Mass: 821.075438294
  • Average Mass: 823.935
DBSALT000827
Categories
UNII1RS284BFUI
CAS number158382-37-7
WeightAverage: 787.46
Monoisotopic: 785.0987615
Chemical FormulaC26H40Cl4N5O10PS
InChI KeyOJLHWPALWODJPQ-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]-C-hydroxycarbonimidoyl}ethyl]-C-hydroxycarbonimidoyl}butanoic acid
SMILES
[H][C@](N)(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
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentOligopeptides
Alternative Parents
Substituents
  • Alpha-oligopeptide
  • Gamma-glutamyl alpha peptide
  • Glutamine or derivatives
  • N-acyl-alpha-amino acid
  • N-acyl-alpha amino acid or derivatives
  • Alpha-amino acid amide
  • Alpha-amino acid
  • N-substituted-alpha-amino acid
  • Alpha-amino acid or derivatives
  • L-alpha-amino acid
  • Nitrogen mustard
  • Phosphoric monoester diamide
  • Monocyclic benzene moiety
  • Dicarboxylic acid or derivatives
  • Fatty amide
  • N-acyl-amine
  • Fatty acyl
  • Organic phosphoric acid amide
  • Benzenoid
  • Organic phosphoric acid derivative
  • Phosphoric acid ester
  • Sulfonyl
  • Sulfone
  • Amino acid or derivatives
  • Amino acid
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Carboxylic acid
  • Organohalogen compound
  • Hydrocarbon derivative
  • Organic nitrogen compound
  • Alkyl halide
  • Primary aliphatic amine
  • Organic oxygen compound
  • Carbonyl group
  • Alkyl chloride
  • Organochloride
  • Organonitrogen compound
  • Organooxygen compound
  • Organosulfur compound
  • Primary amine
  • Organic oxide
  • Amine
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationIntended for the treatment of various forms of cancer.
PharmacodynamicsNot Available
Mechanism of actionS-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.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half life18 min
ClearanceNot Available
ToxicityCanfosfamide-related toxicities included grade 1-2 nausea, vomiting, fatigue, transient microscopic hematuria, and anemia.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.8011
Blood Brain Barrier-0.5714
Caco-2 permeable-0.6575
P-glycoprotein substrateSubstrate0.5368
P-glycoprotein inhibitor INon-inhibitor0.7168
P-glycoprotein inhibitor IINon-inhibitor0.988
Renal organic cation transporterNon-inhibitor0.9319
CYP450 2C9 substrateNon-substrate0.7047
CYP450 2D6 substrateNon-substrate0.8022
CYP450 3A4 substrateNon-substrate0.6248
CYP450 1A2 substrateNon-inhibitor0.8303
CYP450 2C9 inhibitorNon-inhibitor0.7946
CYP450 2D6 inhibitorNon-inhibitor0.8697
CYP450 2C19 inhibitorNon-inhibitor0.751
CYP450 3A4 inhibitorNon-inhibitor0.6174
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9628
Ames testNon AMES toxic0.5106
CarcinogenicityNon-carcinogens0.7611
BiodegradationReady biodegradable0.6223
Rat acute toxicity2.5940 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.869
hERG inhibition (predictor II)Non-inhibitor0.7566
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0358 mg/mLALOGPS
logP-0.54ALOGPS
logP-1.4ChemAxon
logS-4.3ALOGPS
pKa (Strongest Acidic)1.53ChemAxon
pKa (Strongest Basic)9.14ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count13ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area232.72 Å2ChemAxon
Rotatable Bond Count25ChemAxon
Refractivity176.81 m3·mol-1ChemAxon
Polarizability73.55 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General References
  1. 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. [PubMed:12738715 ]
  2. 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. [PubMed:15173075 ]
  3. 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. [PubMed:16014111 ]
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
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
Molecular Weight:
23355.625 Da
References
  1. 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. [PubMed:16014111 ]
  2. 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. [PubMed:12738715 ]
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Drug created on October 21, 2007 16:23 / Updated on August 17, 2016 12:24