Cell-based screening and compounds that modulate GaINAc-transferases
Provided herein are small molecule-inhibitors of site-specific O-glycosylation and the identification of such using cell-based fluorescent biosensors. Also provided herein are methods of treating kidney disease and cancer, such as breast cancer.
1. A method for treating chronic kidney disease in a patient, comprising, inhibiting O-glycosylation in the patient by administering to the patient a GalNAc transferase-3 inhibitor having the following structure:
or a pharmaceutically-acceptable salt thereof, in an amount effective to treat chronic kidney disease in a patient.
2. The method of claim 1 , wherein the GalNAc transferase-3 inhibitor lowers endocrine hormone fibroblast growth factor-23 activity in a patient, thereby regulating phosphate homeostasis and improving chronic kidney disease in the patient.
3. The method of claim 2 , wherein the GalNAc transferase-3 inhibitor lowers endocrine hormone fibroblast growth factor-23 activity in a patient by promoting cleavage of endocrine hormone fibroblast growth factor-23 by furin.
4. The method of claim 1 , wherein the GalNAc transferase-3 inhibitor is administered to the patient in a unit dose or multiple doses ranging from 0.01 to 50 mg/kg.
5. The method of claim 1 , wherein the GalNAc transferase-3 inhibitor is administered to the patient in a unit dose or multiple doses ranging from 10 to 25 mg/kg of weight of the patient.