This technology describes the synthesis and characterization of small molecule NT5C2 inhibitors for the treatment of relapsed and chemotherapy-resistant acute lymphoblastic leukemia (ALL) and T-cell acute lymphoblastic leukemia (T-ALL).
ALL and T-ALL are aggressive blood cancers in which relapse is common and resistance to therapy remains a substantial challenge. Gain-of-function mutations in the cytosolic nucleotidase 2 gene (NT5C2) have been identified as a major contributor to this resistance through inactivation of nucleoside-analog chemotherapy drugs. In view of this, a method of inhibiting NT5C2 activity will be needed to improve treatment outcomes for chemotherapy-resistant patients.
This technology identifies HTP-2 as a potent inhibitor of NT5C2 and describes the synthesis and characterization of HTP-2 analogues for treatment of chemotherapy-resistant and relapsed ALL and T-ALL. In a dose-dependent manner, these NT5C2 inhibitors potentiate the ability of 6-MP, a chemotherapy agent, to eliminate NT5C2-mutant mouse lymphoblasts. As such, this technology can be used in combination with existing chemotherapies to more efficaciously treat resistant cases of ALL and T-ALL.
This technology has been validated in NT5C2 R367Q mutant mouse lymphoblasts.
IR CU18358, CU19220
Licensing Contact: Joan Martinez