molecules of the month

compound 15

NaPi2b inhibitor

preclinical (hyperphosphatemia)

in-house compound screen + optimization

J. Med. Chem.

Kyowa Kirin Co., Ltd.

NaPi2b inhibitor - Kyowa Kirin Co., Ltd.
1 min read

Compound 15 is a gut-restricted inhibitor of NaPi2b, a sodium-dependent phosphate transport protein in the solute carrier (SLC) family. NaPi2b is expressed on the apical side of the small intestine and contributes to absorption of inorganic phosphate in the diet. Chronic kidney disease patients have elevated serum phosphate levels and need dialysis to remove excess phosphate. Oral phosphate binder therapies such as sevelamer hydrochloride and lanthanum carbonate that prevent phosphate absorption have non-ideal patient adherence due to pill burden and GI side effects. NaPi2b, however, is also expressed in the lungs and testes, and systemic inhibition is undesirable from a safety perspective. One systemic NaPi2b inhibitor with an undisclosed structure, ASP3325, has been tested in humans but was ineffective in…

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