Cystemustine

Cystemustine is a DNA inhibitor (a chloroethyl nitrosourea, CENU). Cystemustine can cause DNA cross-linking, thereby inhibiting the proliferation of tumor cells. Cystemustine can also exert cytotoxic effects by interfering with the cell cycle, inducing cell re-differentiation, and altering phospholipid metabolism. Cystemustine exhibits high anti-tumor activity and a relatively short plasma half-life in mice. Cystemustine can be used for the study of various malignant tumors, including melanoma, glioma, renal cancer, head and neck cancer, and colorectal cancer, etc^{[1][2][3][4][5][6]}. In Vitro:Cystemustine (100, 200 μM, 2 h) causes no significant DNA damage alone, but combination with O6-benzyl-N2-acetylguanosine (BNAG) significantly increases DNA lesions in M3Dau cells^[3].
Cystemustine (50 μM, 4 h) causes cytotoxicity causes cytotoxicity in M4Beu cells, but its effect is enhanced when combined with lGgBZ (an O6-alkylguanine-DNA alkyltransferase inhibitor)^[6]. In Vivo:Cystemustine (35 mg/kg, i.v., single dose for 55 days) shows a large-amplitude diurnal rhythm toxicity variation with the lowest toxicity level of 15-19 hours after light onset (HALO) and highest level of 7 HALO^[2].
Cystemustine (15 mg/kg, i.v. or injected directly into the tumor, at days 1-19) induces deep alterations concerning cell morphology, cell cycle, and melanin content in melanoma mice model^[4].
Cystemustine (15 mg/kg, injected directly into the tumor, at days 11-18) makes melanoma tumors a new phospholipid metabolism phenotype in mice model^[5].