Sodium Phosphate Cotransporter Inhibitor

Atidafonat is an orally active sodium-dependent phosphate transporter inhibitor, with IC₅₀ values of 6.8, 1.5, and 1.7 μM against human NaPi-IIb, PiT-1, PiT-2, respectively; and IC₅₀ values of 3.9, 1.9, and 1.7 μM against rat NaPi-IIb, PiT-1, PiT-2, respectively. Atidafonat inhibits intestinal phosphate absorption, increases fecal phosphate excretion, reduces urinary phosphate excretion, and decreases the levels of serum phosphate, FGF23, and adult parathyroid hormone. Atidafonat ameliorates ectopic thoracic aortic calcification, renal injury and hyperphosphatemia, and inhibits the expression of fibrosis markers. Atidafonat can be used for the research of hyperphosphatemia and chronic kidney disease-mineral and bone disorder (CKD-MBD).

NaPi2b-IN-1 is a potent and orally active inhibitor of sodium-dependent phosphate transport protein 2b (NaPi2b) with an IC₅₀ of 64 nM. NaPi2b is primarily expressed in the small intestine, lungs, and testes and plays an important role in phosphate homeostasis. NaPi2b-IN-1 has the potential for the research of hyperphosphatemia.

JTP-59557 is an orally active, stereospecific noncompetitive inhibitor of type IIb sodium/phosphate cotransporter (NaPi-IIb). JTP-59557 selectively inhibits type IIb-mediated inorganic phosphate uptake, without affecting Na⁺-independent inorganic phosphate transport or Na⁺-dependent D-glucose (HY-B0389) transport. JTP-59557 also suppresses Na⁺-dependent inorganic phosphate transport in intestinal brush border membrane vesicles. JTP-59557 is applicable to research related to hyperphosphatemia and hyperphosphatemia associated with chronic kidney disease.