A Novel Drug MJ-66 for Treatment of Brain Cancer
Malignant glioma is the most common aggressive adult primary tumor of the central nervous system. Treatments of malignant gliomas include surgery, radiotherapy and adjuvant temozolomide (TMZ) chemotherapy. So far, TMZ is the only clinically used medicine for treatment of malignant gliomas. However, inherent- and acquired resistance to TMZ present major obstacles to successful treatment, and the prognosis of patients with malignant gliomas remains very poor with a mean survival of < 15 months.
MJ-66 displayed better anti-proliferation effect than that of TMZ, on both human malignant glioma cells and drug-resistant human malignant glioma cells. In intracranial glioma xenograft model, MJ-66 (0.14 mg/kg in saline) was administered intraperitoneally once per day for 10 days. Ten days after the cessation of treatment, MJ-66 significantly inhibited tumor growth and increased the survival of the experimental mice without affecting the body weight of the mice. In addition, MJ-66 also displayed excellent anti-proliferation effect on drug-resistant human colon, pancreatic and gastric cancer cells.
MJ-66 is a promising small molecule to be developed as a novel drug for treating malignant glioma and other cancers.
2-Aryl-4-qunazolinones and Their Pharmaceutical Compositions (TW I426903; US8710064B2; US9006239B2; US9045437B2)
1. Liu WT, et al. MJ-66 induces malignant glioma cells G2/M phase arrest and mitotic catastrophe through regulation of cyclin B1/Cdk1 complex. Neuropharmacology. 2014 Aug 5; 86C: 219-227.
2. Hour MJ, et al. Aggravated DNA damage as a basis for enhanced glioma cell killing by MJ-66 in combination with minocycline. Am J Cancer Res. 2014 Sep 6; 4(5):474-83.
3. Hour MJ, et al. Molecular modelling, synthesis, cytotoxicity and anti-tumour mechanisms of 2-aryl-6-substituted quinazolinones as dual-targeted anti-cancer agents. Br J Pharmacol. 2013 Aug; 169(7): 1574-86.
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