Discovery of A Dual Inhibitor of NQO1 and GSTP1 for Treating Malignant Glioblastoma

Application

A small molecule compound to treat Malignant Glioblastoma multiforme.

Key Benefits

Dual inhibition of NQO1 and GSTP1 induces cell death in glioblastoma cells.
Inhibition of NQO1 and GSTP1 by MNPC suppresses tumor growth and elongates the life span of the animals with GBM.

Market Summary

Approximately 30% of patients diagnosed with a brain or spinal cord tumor will survive more than five years. Glioblastoma multiforme (GBM) accounts for about 15% of all brain tumors and occurs in adults between the ages of 45 and 70 years. Effective treatments for brain cancer are limited by the lack of specific therapies for the brain and retardation of drug delivery to brain tumors due to the blood-brain barrier. There is a need for effective therapeutic drugs and strategies for the prolonged survival and improved quality of life for brain tumor patients.

Technical Summary

The researcher at Emory University identified a small molecule inhibitor, 5-methyl-N-(5-nitro-thiazol-2-yl-3-phenyilsozazaole-carboxadmide) (MNPC) which inhibits the proliferation of GBM cells with EGFRvIII mutation by blocking the active enzymatic sites in both NQO1 (NAD(P)H Quinone Dehydrogenase 1)and GSPT1 (eukaryotic peptide chain release factor GTP-binding subunit ERF3A). The inventor found that the knock down of forementioned enzymes significantly decreased overall tumor volumes via the inhibition of ROS (reactive oxygen species) formation. The experiments demonstrated that MNPC (10mg/kg) can suppress tumor growth and even extend the life span of test animals with GBM through inducing cell apoptosis by inhibiting NQO1 and GSTP1. Further SAR studies also suggest that nitazoxanide (NTZ) and tizoxanide (TIZ) displayed comparable anti-proliferative activities towards EGFRvIII mutation presenting human glioma cell line.