Target family: Calcium-sensing receptor (type: gpcr)
Target: CaS receptor

Ligand: Mg2+ (Inorganic)
Interaction type: Agonist
Action: Partial agonist
Ligand approved: no
Median affinity: 2.4 pKd
Reference (Journal): Calcium, magnesium and the control of PTH secretion.
Published in: Bone Miner

Ligand: upacicalcet (Synthetic organic)
Interaction type: Allosteric modulator
Action: Positive
Ligand approved: yes
Approval source: Japan (2021)
Primary target: no
Median affinity: 8.09000015258789 pIC50
Reference (Journal): Upacicalcet Is a Novel Secondary Hyperparathyroidism Drug that Targets the Amino Acid Binding Site of Calcium-Sensing Receptor .
Published in: Mol Pharmacol

Ligand: tecalcet (Synthetic organic)
Interaction type: Allosteric modulator
Action: Positive
Ligand approved: no
Primary target: no
Median affinity:  pKB
Reference (Journal): Biased allosteric modulation at the CaS receptor engendered by structurally diverse calcimimetics.
Published in: Br J Pharmacol

Ligand: tecalcet (Synthetic organic)
Interaction type: Allosteric modulator
Action: Positive
Ligand approved: no
Primary target: no
Median affinity: 6.5 pKd
Reference (Journal): Calcimimetics with potent and selective activity on the parathyroid calcium receptor.
Published in: Proc Natl Acad Sci USA

Ligand: tecalcet (Synthetic organic)
Interaction type: Allosteric modulator
Action: Positive
Ligand approved: no
Primary target: no
Median affinity:  pKB
Reference (Journal): Positive and negative allosteric modulators promote biased signaling at the calcium-sensing receptor.
Published in: Endocrinology

Ligand: spermine (Metabolite)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Median affinity: 3.5 pKd
Reference (Journal): The Ca2+-sensing receptor: a target for polyamines.
Published in: Am J Physiol

Ligand: SB-423562 (Synthetic organic)
Interaction type: Allosteric modulator
Action: Negative
Ligand approved: no
Primary target: no
Median affinity: 7.099999904632568 pIC50
Reference (Journal): An orally active calcium-sensing receptor antagonist that transiently increases plasma concentrations of PTH and stimulates bone formation.
Published in: Bone

Ligand: ronacaleret (Synthetic organic)
Interaction type: Allosteric modulator
Action: Negative
Ligand approved: no
Primary target: no
Median affinity:  pIC50
Reference (Journal): The discovery of novel calcium sensing receptor negative allosteric modulators.
Published in: Bioorg Med Chem Lett

Ligand: (R)-2h [PMID:19625189] (Synthetic organic)
Interaction type: Allosteric modulator
Action: Negative
Ligand approved: no
Primary target: no
Median affinity: 7.389999866485596 pIC50
Reference (Journal): Short-acting 5-(trifluoromethyl)pyrido[4,3-d]pyrimidin-4(3H)-one derivatives as orally-active calcium-sensing receptor antagonists.
Published in: Bioorg Med Chem Lett

Ligand: NPS 2143 (Synthetic organic)
Interaction type: Allosteric modulator
Action: Negative
Ligand approved: no
Primary target: no
Median affinity:  pKB
Reference (Journal): Towards a structural understanding of allosteric drugs at the human calcium-sensing receptor.
Published in: Cell Res

Ligand: NPS 2143 (Synthetic organic)
Interaction type: Allosteric modulator
Action: Negative
Ligand approved: no
Primary target: no
Median affinity:  pIC50
Reference (Journal): Calcilytic compounds: potent and selective Ca2+ receptor antagonists that stimulate secretion of parathyroid hormone.
Published in: J Pharmacol Exp Ther

Ligand: NPS 2143 (Synthetic organic)
Interaction type: Allosteric modulator
Action: Negative
Ligand approved: no
Primary target: no
Median affinity:  pKB
Reference (Journal): Positive and negative allosteric modulators promote biased signaling at the calcium-sensing receptor.
Published in: Endocrinology

Ligand: NPS 2143 (Synthetic organic)
Interaction type: Allosteric modulator
Action: Negative
Ligand approved: no
Primary target: no
Median affinity:  pIC50
Reference (Journal): Discovery and structure-activity relationships of 2-benzylpyrrolidine-substituted aryloxypropanols as calcium-sensing receptor antagonists.
Published in: Bioorg Med Chem Lett

Ligand: NPS 2143 (Synthetic organic)
Interaction type: Allosteric modulator
Action: Negative
Ligand approved: no
Primary target: no
Median affinity:  pKB
Reference (Journal): Impact of clinically relevant mutations on the pharmacoregulation and signaling bias of the calcium-sensing receptor by positive and negative allosteric modulators.
Published in: Endocrinology

Ligand: neomycin (Natural product)
Interaction type: Agonist
Action: Full agonist
Ligand approved: yes
Approval source: FDA (1964)
Median affinity: 4 pKd
Reference (Journal): Cloning and functional expression of a rat kidney extracellular calcium/polyvalent cation-sensing receptor.
Published in: Proc Natl Acad Sci USA

Ligand: Mg2+ (Inorganic)
Interaction type: Agonist
Action: Partial agonist
Ligand approved: no
Median affinity: 2.4 pKd
Reference (Journal): Cloning and functional expression of a rat kidney extracellular calcium/polyvalent cation-sensing receptor.
Published in: Proc Natl Acad Sci USA

Ligand: calindol (Synthetic organic)
Interaction type: Allosteric modulator
Action: Positive
Ligand approved: no
Primary target: no
Median affinity:  pKd
Reference (Journal): N2-benzyl-N1-(1-(1-naphthyl)ethyl)-3-phenylpropane-1,2-diamines and conformationally restrained indole analogues: development of calindol as a new calcimimetic acting at the calcium sensing receptor.
Published in: Bioorg Med Chem Lett

Ligand: calindol (Synthetic organic)
Interaction type: Allosteric modulator
Action: Positive
Ligand approved: no
Primary target: no
Median affinity: 6.300000190734863 pKB
Reference (Journal): Biased allosteric modulation at the CaS receptor engendered by structurally diverse calcimimetics.
Published in: Br J Pharmacol

Ligand: calindol (Synthetic organic)
Interaction type: Allosteric modulator
Action: Positive
Ligand approved: no
Primary target: no
Median affinity:  pKd
Reference (Journal): Positive and negative allosteric modulators of the Ca2+-sensing receptor interact within overlapping but not identical binding sites in the transmembrane domain.
Published in: J Biol Chem

Ligand: Ca2+ (Inorganic)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Median affinity: 2.4 pKd
Reference (Journal): Glyceraldehyde-3-phosphate dehydrogenase selectively binds AU-rich RNA in the NAD(+)-binding region (Rossmann fold).
Published in: J Biol Chem

Ligand: Ca2+ (Inorganic)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Median affinity: 2.5 pKd
Reference (Journal): Identification of a novel extracellular cation-sensing G-protein-coupled receptor.
Published in: J Biol Chem

Ligand: Ca2+ (Inorganic)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Median affinity: 2.5 pKd
Reference (Journal): Cloning and functional expression of a rat kidney extracellular calcium/polyvalent cation-sensing receptor.
Published in: Proc Natl Acad Sci USA

Ligand: cinacalcet (Synthetic organic)
Interaction type: Allosteric modulator
Action: Positive
Ligand approved: yes
Approval source: EMA & FDA (2004)
Primary target: yes
Median affinity: 7.300000190734863 pEC50
Reference (Journal): Pharmacodynamics of the type II calcimimetic compound cinacalcet HCl.
Published in: J Pharmacol Exp Ther

Ligand: cinacalcet (Synthetic organic)
Interaction type: Allosteric modulator
Action: Positive
Ligand approved: yes
Approval source: EMA & FDA (2004)
Primary target: yes
Median affinity:  pKB
Reference (Journal): Impact of clinically relevant mutations on the pharmacoregulation and signaling bias of the calcium-sensing receptor by positive and negative allosteric modulators.
Published in: Endocrinology

Ligand: cinacalcet (Synthetic organic)
Interaction type: Allosteric modulator
Action: Positive
Ligand approved: yes
Approval source: EMA & FDA (2004)
Primary target: yes
Median affinity:  pKB
Reference (Journal): Positive and negative allosteric modulators promote biased signaling at the calcium-sensing receptor.
Published in: Endocrinology

Ligand: cinacalcet (Synthetic organic)
Interaction type: Allosteric modulator
Action: Positive
Ligand approved: yes
Approval source: EMA & FDA (2004)
Primary target: yes
Median affinity:  pKB
Reference (Journal): Towards a structural understanding of allosteric drugs at the human calcium-sensing receptor.
Published in: Cell Res

Ligand: cinacalcet (Synthetic organic)
Interaction type: Allosteric modulator
Action: Positive
Ligand approved: yes
Approval source: EMA & FDA (2004)
Primary target: yes
Median affinity:  pKB
Reference (Journal): Biased allosteric modulation at the CaS receptor engendered by structurally diverse calcimimetics.
Published in: Br J Pharmacol

Ligand: compound 17 [PMID: 15300839] (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity: 5.3 pIC50
Reference (Journal): N(1)-Arylsulfonyl-N(2)-(1-(1-naphthyl)ethyl)-1,2-diaminocyclohexanes: a new class of calcilytic agents acting at the calcium-sensing receptor.
Published in: Chembiochem

Ligand: compound 18c [PMID:19143533] (Synthetic organic)
Interaction type: Allosteric modulator
Action: Negative
Ligand approved: no
Primary target: no
Median affinity: 7.119999885559082 pIC50
Reference (Journal): Discovery and structure-activity relationships of trisubstituted pyrimidines/pyridines as novel calcium-sensing receptor antagonists.
Published in: J Med Chem

Ligand: compound (S)-3h [PMID: 15686947] (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity: 6.9 pIC50
Reference (Journal): Discovery and structure-activity relationships of 2-benzylpyrrolidine-substituted aryloxypropanols as calcium-sensing receptor antagonists.
Published in: Bioorg Med Chem Lett

Ligand: 1-arylmethylpyrrolidin-2-yl ethanol amine (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity: 4.3 pIC50
Reference (Journal): Discovery of novel 1-arylmethyl pyrrolidin-2-yl ethanol amines as calcium-sensing receptor antagonists.
Published in: Bioorg Med Chem Lett

Ligand: 2-methyl-3-phenethyl-3H-pyrimidin-4-one (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity: 7 pIC50
Reference (Journal): Design, new synthesis, and calcilytic activity of substituted 3H-pyrimidin-4-ones.
Published in: Bioorg Med Chem Lett

Ligand: AC265347 (Synthetic organic)
Interaction type: Allosteric modulator
Action: Positive
Ligand approved: no
Primary target: no
Median affinity:  pKB
Reference (Journal): Biased allosteric modulation at the CaS receptor engendered by structurally diverse calcimimetics.
Published in: Br J Pharmacol

Ligand: AC265347 (Synthetic organic)
Interaction type: Allosteric modulator
Action: Positive
Ligand approved: no
Primary target: no
Median affinity:  pEC50
Reference (Journal): Characterization of highly efficacious allosteric agonists of the human calcium-sensing receptor.
Published in: J Pharmacol Exp Ther

Ligand: encaleret (Synthetic organic)
Interaction type: Allosteric modulator
Action: Negative
Ligand approved: no
Primary target: no
Median affinity: 7.900000095367432 pIC50
Reference (Journal): Discovery of a potent and short-acting oral calcilytic with a pulsatile secretion of parathyroid hormone.
Published in: ACS Med Chem Lett

Ligand: AC265347 (Synthetic organic)
Interaction type: Allosteric modulator
Action: Positive
Ligand approved: no
Primary target: no
Median affinity:  pKB
Reference (Journal): Towards a structural understanding of allosteric drugs at the human calcium-sensing receptor.
Published in: Cell Res

Ligand: ATF936 (Synthetic organic)
Interaction type: Allosteric modulator
Action: Negative
Ligand approved: no
Primary target: no
Median affinity: 8.899999618530273 pIC50
Reference (Journal): 1-Alkyl-4-phenyl-6-alkoxy-1H-quinazolin-2-ones: a novel series of potent calcium-sensing receptor antagonists.
Published in: J Med Chem

Ligand: AXT914 (Synthetic organic)
Interaction type: Allosteric modulator
Action: Negative
Ligand approved: no
Primary target: no
Median affinity: 8.850000381469727 pIC50
Reference (Journal): Calcilytics: antagonists of the calcium-sensing receptor for the treatment of osteoporosis.
Published in: Future Med Chem

Ligand: calhex 231 (Synthetic organic)
Interaction type: Allosteric modulator
Action: Negative
Ligand approved: no
Primary target: no
Median affinity: 6.400000095367432 pIC50
Reference (Journal): Modeling and mutagenesis of the binding site of Calhex 231, a novel negative allosteric modulator of the extracellular Ca(2+)-sensing receptor.
Published in: J Biol Chem

Ligand: etelcalcetide (Peptide)
Interaction type: Allosteric modulator
Action: Positive
Ligand approved: yes
Approval source: EMA (2016), FDA (2017)
Primary target: no
Median affinity: 4.599999904632568 pEC50
Reference (Journal): Pharmacology of AMG 416 (Velcalcetide), a novel peptide agonist of the calcium-sensing receptor, for the treatment of secondary hyperparathyroidism in hemodialysis patients.
Published in: J Pharmacol Exp Ther

Ligand: evocalcet (Synthetic organic)
Interaction type: Allosteric modulator
Action: Positive
Ligand approved: no
Primary target: yes
Median affinity: 7.03000020980835 pEC50
Reference (Journal): Discovery of evocalcet, a next-generation calcium-sensing receptor agonist for the treatment of hyperparathyroidism.
Published in: Bioorg Med Chem Lett

Ligand: L-tryptophan (Metabolite)
Interaction type: Allosteric modulator
Action: Positive
Ligand approved: no
Median affinity:  pKd
Reference (Journal): L-amino acids regulate parathyroid hormone secretion.
Published in: J Biol Chem

Ligand: L-tryptophan (Metabolite)
Interaction type: Allosteric modulator
Action: Positive
Ligand approved: no
Median affinity:  pKd
Reference (Journal): L-amino acid sensing by the extracellular Ca2+-sensing receptor.
Published in: Proc Natl Acad Sci USA