Canfosfamide

Identification

Name
Canfosfamide
Accession Number
DB04972
Type
Small Molecule
Groups
Investigational
Description

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

Structure
Thumb
Synonyms
Not Available
External IDs
TER 286 / TLK 286
Product Ingredients
IngredientUNIICASInChI Key
Canfosfamide hydrochloride1LI341K7NQ439943-59-6NECZZOFFLFZNHL-XVGZVFJZSA-N
International/Other Brands
Telcyta
Categories
UNII
1RS284BFUI
CAS number
158382-37-7
Weight
Average: 787.46
Monoisotopic: 785.0987615
Chemical Formula
C26H40Cl4N5O10PS
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]-C-hydroxycarbonimidoyl}ethyl]-C-hydroxycarbonimidoyl}butanoic acid
SMILES
[H][[email protected]](N)(CCC(O)=N[[email protected]@]([H])(CS(=O)(=O)CCOP(=O)(N(CCCl)CCCl)N(CCCl)CCCl)C(O)=N[[email protected]@]([H])(C(O)=O)C1=CC=CC=C1)C(O)=O

Pharmacology

Indication

Intended for the treatment of various forms of cancer.

Structured Indications
Not Available
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.

TargetActionsOrganism
UGlutathione S-transferase PNot AvailableHuman
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
Toxicity

Canfosfamide-related toxicities included grade 1-2 nausea, vomiting, fatigue, transient microscopic hematuria, and anemia.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

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
PubChem Compound
5312109
PubChem Substance
175426923
ChemSpider
4471543
ChEBI
135883
ChEMBL
CHEMBL2111086

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentCancer, Ovarian / Fallopian Tube Cancer / Primary Peritoneal Cavity Cancer1
2CompletedTreatmentLung Cancers1
2CompletedTreatmentLymphoma, B Cell / Mantle Cell Lymphoma (MCL) / Multiple Myeloma (MM)1
3TerminatedTreatmentNeoplasms, Ovarian1

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
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 FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

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
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
show 35 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
Not 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
Uniprot Name
Glutathione S-transferase P
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]

Drug created on October 21, 2007 16:23 / Updated on December 01, 2017 17:17