TY - JOUR
T1 - G protein-coupled receptors as anabolic drug targets in osteoporosis
AU - Diepenhorst, Natalie
AU - Rueda, Patricia
AU - Cook, Anna E.
AU - Pastoureau, Philippe
AU - Sabatini, Massimo
AU - Langmead, Christopher J.
PY - 2018/4/1
Y1 - 2018/4/1
N2 - Osteoporosis is a progressive bone disorder characterised by imbalance between bone building (anabolism) and resorption (catabolism). Most therapeutics target inhibition of osteoclast-mediated bone resorption, but more recent attention in early drug discovery has focussed on anabolic targets in osteoblasts or their precursors. Two marketed agents that display anabolic properties, strontium ranelate and teriparatide, mediate their actions via the G protein-coupled calcium-sensing and parathyroid hormone-1 receptors, respectively. This review explores their activity, the potential for improved therapeutics targeting these receptors and other putative anabolic GPCR targets, including Smoothened, Wnt/Frizzled, relaxin family peptide, adenosine, cannabinoid, prostaglandin and sphingosine-1-phosphate receptors.
AB - Osteoporosis is a progressive bone disorder characterised by imbalance between bone building (anabolism) and resorption (catabolism). Most therapeutics target inhibition of osteoclast-mediated bone resorption, but more recent attention in early drug discovery has focussed on anabolic targets in osteoblasts or their precursors. Two marketed agents that display anabolic properties, strontium ranelate and teriparatide, mediate their actions via the G protein-coupled calcium-sensing and parathyroid hormone-1 receptors, respectively. This review explores their activity, the potential for improved therapeutics targeting these receptors and other putative anabolic GPCR targets, including Smoothened, Wnt/Frizzled, relaxin family peptide, adenosine, cannabinoid, prostaglandin and sphingosine-1-phosphate receptors.
KW - Bone anabolism
KW - Calcium-sensing receptor
KW - Frizzled receptors
KW - G protein-coupled receptors (GPCRs)
KW - Osteoporosis
KW - Parathyroid hormone receptor
UR - http://www.scopus.com/inward/record.url?scp=85034584159&partnerID=8YFLogxK
U2 - 10.1016/j.pharmthera.2017.10.015
DO - 10.1016/j.pharmthera.2017.10.015
M3 - Review Article
AN - SCOPUS:85034584159
SN - 0163-7258
VL - 184
SP - 1
EP - 12
JO - Pharmacology & Therapeutics
JF - Pharmacology & Therapeutics
ER -