Therapeutic agents for reducing parathyroid hormone levels

Abstract

Compounds having activity for lowering parathyroid hormone levels are described. In one embodiment, the compounds are comprised of a contiguous sequence of subunits, X 1 -X 2 -X 3 -X 4 -X 5 -X 6 -X 7 , wherein the X 1 subunit comprises a thiol-containing moiety and the distribution of charge on the X 2 -X 7 subunits provides the desired activity. Methods of using the compounds for treating hyperparathyroidism, bone disease and/or hypercalcemic disorders are also described, and in particular, methods for lowering plasma PTH and serum calcium are provided. The compounds can be used to treat subjects having, for example: primary, secondary or tertiary hyperparathyroidism; hypercalcemia of malignancy; metastatic bone disease; or osteoporosis.

1 . A peptide comprising the amino acid sequence X 1 -X 2 -X 3 -X 4 -X 5 -X 6 -X 7 ,
 wherein:   X 1  is a subunit comprising a thiol-containing group;   X 5  is a cationic subunit;   X 6  is a non-cationic subunit;   X 7  is a cationic subunit; and   at least one of X 2 , X 3  and X 4  is independently a cationic subunit.