Chlorambucil

Chlorambucil (CB-1348), an orally active antineoplastic agent, is a CNS-penetrant bifunctional alkylating agent belonging to the nitrogen mustard group. Chlorambucil can be used for the research of lymphocytic leukemia, ovarian and breast carcinomas, and Hodgkin’s disease^[1][2][3][4]. IC50 & Target:DNA Alkylator^[1] In Vitro:Chlorambucil can deprive the function of complementary strands of DNA molecules via alkalization-induced cross interaction, and then inhibits tumor cell proliferation. Chlorambucil (0, 2.5, 5, 10 μM) exhibits slight inhibitory effect on Raji cell apoptosis, but potently increases DR4 and DR5 mRNA expression in Raji cells. Chlorambucil (10 μM) in combination with Tumor necrosis factor (TNF) related apoptosis inducing ligand (TRAIL, 80 ng/ml) has synergistic effect on Raji cell apoptosis and inhibition on proliferation^[1].
Chlorambucil is a DNA alkylator at high doses and, at lower doses, acts as an inhibitor of synthesis of nuclear proteins, particularly histones. Increasing doses are associated with a higher frequency of apoptosis, whereas long-term maintenance therapy has been associated with mutations of the p53 gene, leading to secondary malignancies^[4]. In Vivo:Chlorambucil (0.2 mg/kg, p.o.) in combination with levamisole (5 mg/kg) has enhanced anti-cancer effect on Ehrlich ascites carcinoma which elevates apoptosis of Ehrlich ascites carcinoma and the survival rate of the mice. However, Chlorambucil exhibits adverse effects on the liver and kidneys of mice^[2].