Canfosfamide Explained

Legal Status:	Investigational
Synonyms:	TLK286
Cas Number:	158382-37-7
Cas Supplemental:	HCl 439943-59-6
Pubchem:	5312109
Chemspiderid:	4471543
Chebi:	135883
Chembl:	2111086
Unii:	1RS284BFUI
Drugbank:	DB04972
Iupac Name:	(2S)-2-Amino-5-(2R)-3-[2-[bis[bis(2-chloroethyl)amino]phosphoryloxy]ethylsulfonyl]-1-(R)-carboxy(phenyl)methylamino]-1-oxopropan-2-ylamino]-5-oxopentanoic acid
C:	26
H:	40
Cl:	4
N:	5
O:	10
P:	1
S:	1
Stdinchi:	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
Stdinchikey:	OJLHWPALWODJPQ-QNWVGRARSA-N
Smiles:	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

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]}

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.^{[4] [5]}

Clinical trials

Phase I clinical trials evaluated the safety, tolerability, and pharmacokinetics of canfosfamide.^[6] 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.

Notes and References

1. Tew KD . TLK-286: a novel glutathione S-transferase-activated prodrug . Expert Opinion on Investigational Drugs . 14 . 8 . 1047–54 . August 2005 . 16050796 . 10.1517/13543784.14.8.1047 .
2. Vergote I, Finkler N, del Campo J, Lohr A, Hunter J, Matei D, Kavanagh J, Vermorken JB, Meng L, Jones M, Brown G, Kaye S . Phase 3 randomised study of canfosfamide (Telcyta, TLK286) versus pegylated liposomal doxorubicin or topotecan as third-line therapy in patients with platinum-refractory or -resistant ovarian cancer . European Journal of Cancer . Oxford, England . 45 . 13 . 2324–32 . September 2009 . 19515553 . 10.1016/j.ejca.2009.05.016 .
3. >Web site: Canfosfamide . AdisInsight . Springer Nature Switzerland AG .
4. Montero AJ, Jassem J . Cellular redox pathways as a therapeutic target in the treatment of cancer . Drugs . 71 . 11 . 1385–96 . July 2011 . 21812504 . 10.2165/11592590-000000000-00000 .
5. Brüning A, Mylonas I . New emerging drugs targeting the genomic integrity and replication machinery in ovarian cancer . Archives of Gynecology and Obstetrics . 283 . 5 . 1087–96 . May 2011 . 21082186 . 10.1007/s00404-010-1757-x .
6. 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 . Clinical Cancer Research . 9 . 5 . 1628–38 . May 2003 . 12738715 .
7. 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 . International Journal of Gynecological Cancer . 15 . 4 . 593–600 . 2005 . 16014111 . 10.1111/j.1525-1438.2005.00114.x .