Semustine

Semustine is an orally active, blood-brain barrier permeable antitumor alkylating agent with a binding affinity of 1.53 × 10³ M^-1 for guanine and thymine residues in bovine DNA. Semustine undergoes major groove-directed alkylation at guanine residues to form O6-chloroethylguanine and N1-O6-ethanoguanine adducts, and generates dG-dC interstrand crosslinks. Semustine induces partial B- to C-type transition of DNA, base stacking and helical structure distortion, mild dehydration, as well as partial DNA double-strand unwinding. Semustine can be used in research related to Lewis lung cancer, leukemia, Hodgkin's lymphoma, malignant melanoma, glioma, and diffuse large B-cell lymphoma^[1][2]. In Vitro:Semustine (0.525-4.2 mM; 2-24 h) binds to calf thymus DNA via major-groove-directed alkylation, initially interacting with thymine residues before forming dG-dC interstrand cross-links in a concentration- and time-dependent manner, and induces partial transition of DNA from native B-conformation to C-form^[1].
Semustine binds to calf thymus DNA with moderate affinity, having a binding constant of 1.53 × 10³ M^-1, and induces DNA base alkylation leading to localized duplex denaturation^[1].