MN58b: An Effective Choline Kinase Inhibitor in the Treatment of Rat Brain Gliomas

Manoj Kumar¹, Sean Arlauckas¹, Sona Saksena¹, Gaurav Verma¹, Ranjit Ittyerah¹, Anatoliy V. Popov¹, Harish Poptani¹, Edward James Delikatny¹

Abnormal choline metabolism is a hallmark in cancer diagnosis and is associated with oncogenesis and tumor progression. Increased total choline, predominantly arising from phosphocholine is consistently observed in both pre-clinical tumor models as well as in human tumor studies by 1H MRS. Inhibition of choline kinase using specific choline kinase inhibitors, such as MN58b is a promising new strategy for treatment of brain tumors. We demonstrate the efficacy of MN58b in specifically suppressing total choline levels in an intracranial rat brain tumor model. In-vitro and in-vivo assays were used to characterize the effects of MN58b on tumor cells and on orthotopically grown gliomas in a rat model.