Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C24H25ClN2O2 |
| Molecular Weight | 408.921 |
| Optical Activity | ( + ) |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CC(C)(CC1=CC=C2C=CC=CC2=C1)NC[C@@H](O)COC3=C(C#N)C(Cl)=CC=C3
InChI
InChIKey=PZUJQWHTIRWCID-HXUWFJFHSA-N
InChI=1S/C24H25ClN2O2/c1-24(2,13-17-10-11-18-6-3-4-7-19(18)12-17)27-15-20(28)16-29-23-9-5-8-22(25)21(23)14-26/h3-12,20,27-28H,13,15-16H2,1-2H3/t20-/m1/s1
NPS-2143 is a novel potent and selective antagonist of Ca(2+) receptor with IC50 of 43 nM. Blockage of CaSR with NPS-2143 has being shown to prevent the development of pulmonary hypertension and right ventricular hypertrophy in animal models of pulmonary hypertension. The use of calcilytics, antagonists of CaSR, may be a novel therapeutic approach for PAH patients. Calcilytic drugs have been researched as potential treatments for osteoporosis, and as the first such compound developed, NPS-2143 is still widely used in research into the CaSR receptor as well as design of newer calcilytic agents. When administered together with an antiresorptive agent (estradiol), NPS 2143 causes an increase in trabecular bone volume and bone mineral density in osteopenic rats.
Originator
Sources: http://adisinsight.springer.com/drugs/800010915 | https://www.ncbi.nlm.nih.gov/pubmed/19492813
Curator's Comment: # NPS Pharmaceuticals/GlaxoSmithKline
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
| 43.0 nM [IC50] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | Unknown Approved UseUnknown |
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| Primary | Unknown Approved UseUnknown |
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| Primary | Unknown Approved UseUnknown |
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| Primary | Unknown Approved UseUnknown |
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| Primary | Unknown Approved UseUnknown |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Calcilytic compounds: potent and selective Ca2+ receptor antagonists that stimulate secretion of parathyroid hormone. | 2001 Oct |
|
| Discovery and structure-activity relationships of 2-benzylpyrrolidine-substituted aryloxypropanols as calcium-sensing receptor antagonists. | 2005 Feb 15 |
|
| Molecular determinants of non-competitive antagonist binding to the mouse GPRC6A receptor. | 2009 Nov-Dec |
Sample Use Guides
In Vivo Use Guide
Curator's Comment: Can be used orally: https://www.ncbi.nlm.nih.gov/pubmed/27667315
Rats: the rats were infused intravenously (0.1 ml/kg/min) for 120 min with NPS-2143 (0.1 umol/kg/min) or vehicle, a 20% aqueous solution of 2-hydroxypropyl-Beta-cyclodextrin.
Route of Administration:
Intravenous
In Vitro Use Guide
Curator's Comment: Increasing the concentration of extracellular Ca2+ from 1.0 to 1.75 mM
caused a rapid and transient increase followed by a lower yet
more prolonged increase in [Ca2+]i in HEK 293 4.0-7 cells
expressing the human Ca2+ receptor. Preincubation
of these cells with NPS-2143 caused a concentration-dependent
inhibition of the cytoplasmic Ca2+ response to extracellular
Ca2+. When NPS-2143 (300 nM) was added to
cells during the prolonged phase of the response, there was
an immediate fall in [Ca2+]i to baseline values.
NPS-2143 blocked (IC50 of 43 nM) increases in cytoplasmic Ca2+ concentrations [Ca2+]i elicited by activating the Ca2+ receptor in HEK 293 cells expressing the human Ca2+ receptor. NPS-2143, even when tested at much higher concentrations (3 uM), did not affect the activity of a number of other G protein-coupled receptors, including those most structurally homologous to the Ca2+ receptor.
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DB05695
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6918446
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NPS-2143
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DTXSID10426075
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284035-33-2
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Z25PJ77W7V
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ACTIVE MOIETY
SALT/SOLVATE (PARENT)
