| abstract |
Compounds, compositions, and methods for inhibition of ENPP1 are provided. Aspects of the objective methods include contacting a sample with an ENPP1 inhibitory compound to inhibit the cGAMP hydrolysis activity of ENPP1. In some cases, the ENPP1 inhibitory compound is impermeable to cells. ENPP1 inhibitory compounds can act extracellularly to block cGAMP degradation. Pharmaceutical compositions and methods for treating cancer are also provided. Aspects of the methods include administering to a subject a therapeutically effective amount of an inhibitor of ENPP1 to treat the subject for cancer. In certain cases, the cancer is a solid tumor cancer. Methods of administering radiation therapy to a subject in conjunction with administering an ENPP1 inhibitor to the subject are also provided. Radiotherapy can be administered in the target methods at a dose and/or frequency effective to reduce radiation damage to the subject, but still instigate an immune response. |