TABLE 13
Negative allosteric modulators of the calcium sensing receptor (“calcilytics”)
The potencies of the compounds have indicative value only and should be compared with caution. Most compounds shown are representative examples of a chemical series.
| Compound | Structure | Potency (IC50) | Comments | References |
|---|---|---|---|---|
| I: NPS 2143 |  | 43 nM | The first calcilytic compound | Nemeth et al., 2001 |
| II: Calhex 231 |  | 390 nM | Petrel et al., 2003; Kessler et al., 2006 | |
| III: Ronacaleret |  | 150 μM | First results in humans negative | Fitzpatrick et al., 2009; Trivedi et al., 2009 |
| IV |  | 25 nM | Mixture of two diastereoisomers; robust PTH response in rats at 10 mg/kg p.o. | Balan et al., 2009 |
| V |  | 76 nM | Transient stimulation of PTH secretion in vivo | Arey et al., 2005; Yang et al., 2009 |
| VI |  | 120 nM | Yang et al., 2005 | |
| VII |  | 300 nM | Shcherbakova et al., 2005 | |
| VIII |  | 4.4 nM | Good in vivo activity in rats and dogs with a close analog | Widler et al., 2010 |
| IX: R = H |  | R = H: 200 nM | Drug (R = H)/prodrug (R = Et) pairs. Prodrugs transiently increase PTH in vivo, SB-423557 stimulates bone formation | Marquis et al., 2009b |
| R = Et | ||||
| X: R = H,xs SB-423562 |  | R = H: 73 nM | Kumar et al., 2010 | |
| R = Et, SB-423557 |