Canfosfamide

Chemical compound From Wikipedia, the free encyclopedia

Canfosfamide (development code TLK286) an investigational anticancer drug that has been evaluated for its potential efficacy in treating a variety of solid tumors. TLK286 functions as a prodrug activated by the enzyme glutathione S-transferase P1-1 (GST P1-1), which is often overexpressed in cancer cells, leading to selective cytotoxicity towards tumor cells compared to normal cells.[1][2][3][4]

Other namesTLK286
Legal status
  • Investigational
CAS Number
PubChem CID
Quick facts Clinical data, Other names ...
Canfosfamide
Clinical data
Other namesTLK286
Legal status
Legal status
  • Investigational
Identifiers
  • (2S)-2-Amino-5-[[(2R)-3-[2-[bis[bis(2-chloroethyl)amino]phosphoryloxy]ethylsulfonyl]-1-[[(R)-carboxy(phenyl)methyl]amino]-1-oxopropan-2-yl]amino]-5-oxopentanoic acid
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC26H40Cl4N5O10PS
Molar mass787.46 g·mol−1
3D model (JSmol)
  • C1=CC=C(C=C1)[C@H](C(=O)O)NC(=O)[C@H](CS(=O)(=O)CCOP(=O)(N(CCCl)CCCl)N(CCCl)CCCl)NC(=O)CC[C@@H](C(=O)O)N
  • 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
  • Key:OJLHWPALWODJPQ-QNWVGRARSA-N
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Mechanism of action

Canfosfamide is specifically activated in the presence of elevated GST P1-1, which is commonly found in various cancer types. Upon activation, it is converted into an alkylating agent that induces DNA damage, leading to apoptosis in cancer cells.[1][2][3][5][6]

Clinical trials

Phase I clinical trials evaluated the safety, tolerability, and pharmacokinetics of canfosfamide.[1] Phase II trials evaluated clinical activity in various tumor types, especially ovarian cancer and non-small cell lung cancer.[7] Phase III trials focused on its efficacy as part of combination therapy, particularly with standard chemotherapeutic agents. However, the trials did not demonstrate significant improvement in overall survival when compared to standard treatments alone.[3]

References

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