(2R)-L-gamma-Glutamyl-3-((2-((bis(bis(2-chloroethyl)amino)phosphinyl)oxy) ethyl)sulfonyl)- L-alanyl-2-phenylglycine

Canfosfamide (TLK-286, TER286) is a glutathione analogue prodrug that is activated by glutathione S-transferase P1-1 and induces apoptosis. Canfosfamide also inhibits the catalytic kinase activity of DNA-dependent protein kinase (DNA-PK). Canfosfamide produces an anticancer alkylating agent and a glutathione derivative after activation. Canfosfamide can be used to research malignancies[1][2][3].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> Cell Cycle/DNA Damage >> DNA-PK

Signaling Pathways >> PI3K/Akt/mTOR >> DNA-PK

IC50: ~1 µM (DNA-PK)[3]

Canfosfamide (TLK-28) inhibit the catalytic kinase activity of purified DNA-dependent protein kinase (DNA-PK) with an IC50 value of ~1 µM, but causes minimal direct damage to DNA[2]. Canfosfamide (TER286) inhibits MCF-7, NIH-3T3 and M7609 in a dose-dependent manner[3]. Cell Proliferation Assay[3] Cell Line: MCF-7, NIH-3T3 and M7609 Concentration: 0-100 μM Incubation Time: Co-incubated for 2 h then removed and incubated for 5 days in MCF-7; co-incubated for 10 days in NIH-3T3; co-incubated for 48 h in M7609 Result: Inhibited these cancer cell lines in a dose-dependent manner.

Canfosfamide (TER286) exhibits more effective antitumor effect in more frequent administration[3]. Animal Model: BALB/c nude mice (s.c. with tumors of M7609, MX-1 human breast tumor, lung tumor[3] Dosage: 150 mg/kg for M7609 xenografts; 400 mg/kg or 200 mg/kg for other xenografts Administration: i.v., single dosage for M7609 xenograft; i.p., single dosage for other xenografts; i.p., daily for 5 days Result: The best response to TER286 was for the MX-1 human breast tumor treated with an aggressive regimen (daily for 5 days), under which nearly all of the tumors were either severely growth inhibited or substantially regressed.