Evidence map›Paper›PMID 29636377›Full record

ArticleMolecular pharmacology2018

Identification of Global and Ligand-Specific Calcium Sensing Receptor Activation Mechanisms.

Andrew N Keller, Irina Kufareva, Tracy M Josephs, Jiayin Diao, Vyvyan T Mai, Arthur D Conigrave, Arthur Christopoulos, Karen J Gregory, Katie Leach

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Low molecular weight hyaluronan inhibits lung epithelial ion channels by activating the calcium-sensing receptor.Matrix biology : journal of the International Society for Matrix Biology · 2023
    Article
  7. Symmetric activation and modulation of the human calcium-sensing receptor.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  8. Review
  9. Article
  10. Review
  11. Article
  12. Review
  13. Article
  14. Review
  15. Review
  16. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Andrew N KellerDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences and Department of Pharmacology, Monash University, Parkville, Victoria, Australia (A.N.K., T.M.J., J.D., V.T.M., A.C., K.J.G., K.L.); Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, La Jolla, San Diego, California (I.K.); and School of Life and Environmental Sciences, Charles Perkins Centre (D17), University of Sydney, New South Wales, Australia (A.D.C.).
Irina KufarevaDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences and Department of Pharmacology, Monash University, Parkville, Victoria, Australia (A.N.K., T.M.J., J.D., V.T.M., A.C., K.J.G., K.L.); Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, La Jolla, San Diego, California (I.K.); and School of Life and Environmental Sciences, Charles Perkins Centre (D17), University of Sydney, New South Wales, Australia (A.D.C.).
Tracy M JosephsDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences and Department of Pharmacology, Monash University, Parkville, Victoria, Australia (A.N.K., T.M.J., J.D., V.T.M., A.C., K.J.G., K.L.); Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, La Jolla, San Diego, California (I.K.); and School of Life and Environmental Sciences, Charles Perkins Centre (D17), University of Sydney, New South Wales, Australia (A.D.C.).
Jiayin DiaoDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences and Department of Pharmacology, Monash University, Parkville, Victoria, Australia (A.N.K., T.M.J., J.D., V.T.M., A.C., K.J.G., K.L.); Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, La Jolla, San Diego, California (I.K.); and School of Life and Environmental Sciences, Charles Perkins Centre (D17), University of Sydney, New South Wales, Australia (A.D.C.).
Vyvyan T MaiDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences and Department of Pharmacology, Monash University, Parkville, Victoria, Australia (A.N.K., T.M.J., J.D., V.T.M., A.C., K.J.G., K.L.); Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, La Jolla, San Diego, California (I.K.); and School of Life and Environmental Sciences, Charles Perkins Centre (D17), University of Sydney, New South Wales, Australia (A.D.C.).
Arthur D ConigraveDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences and Department of Pharmacology, Monash University, Parkville, Victoria, Australia (A.N.K., T.M.J., J.D., V.T.M., A.C., K.J.G., K.L.); Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, La Jolla, San Diego, California (I.K.); and School of Life and Environmental Sciences, Charles Perkins Centre (D17), University of Sydney, New South Wales, Australia (A.D.C.).
Arthur ChristopoulosDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences and Department of Pharmacology, Monash University, Parkville, Victoria, Australia (A.N.K., T.M.J., J.D., V.T.M., A.C., K.J.G., K.L.); Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, La Jolla, San Diego, California (I.K.); and School of Life and Environmental Sciences, Charles Perkins Centre (D17), University of Sydney, New South Wales, Australia (A.D.C.).
Karen J GregoryDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences and Department of Pharmacology, Monash University, Parkville, Victoria, Australia (A.N.K., T.M.J., J.D., V.T.M., A.C., K.J.G., K.L.); Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, La Jolla, San Diego, California (I.K.); and School of Life and Environmental Sciences, Charles Perkins Centre (D17), University of Sydney, New South Wales, Australia (A.D.C.).
Katie LeachDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences and Department of Pharmacology, Monash University, Parkville, Victoria, Australia (A.N.K., T.M.J., J.D., V.T.M., A.C., K.J.G., K.L.); Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, La Jolla, San Diego, California (I.K.); and School of Life and Environmental Sciences, Charles Perkins Centre (D17), University of Sydney, New South Wales, Australia (A.D.C.) katie.leach@monash.edu karen.gregory@monash.edu.

Funding

AIBP therapyR35HL135737 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MILLER, YURY · 2017 to 2023
$6.5M
AIBP and regulation of neuropathic painR01NS102432 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MILLER, YURY, YAKSH, TONY L. · 2017 to 2021
$3.0M
The structural plasticity of chemokine and gp120 recognition by CCR5R01AI118985 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HANDEL, TRACY M, KUFAREVA, IRINA · 2015 to 2019
$2.7M
Chemokine interaction with CXCR4 and ACKR3: structure and activation mechanismsR01GM117424 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HANDEL, TRACY M, KUFAREVA, IRINA · 2016 to 2019
$2.2M
NHLBI NIH HHS R35 HL135737NIAID NIH HHS R01 AI118985NIGMS NIH HHS R01 GM117424NINDS NIH HHS R01 NS102432
6 · The paper itself

Abstract

Calcium sensing receptor (CaSR) positive allosteric modulators (PAMs) are therapeutically important. However, few are approved for clinical use, in part due to complexities in assessing allostery at a receptor where the endogenous agonist (extracellular calcium) is present in all biologic fluids. Such complexity impedes efforts to quantify and optimize allosteric drug parameters (affinity, cooperativity, and efficacy) that dictate PAM structure-activity relationships (SARs). Furthermore, an underappreciation of the structural mechanisms underlying CaSR activation hinders predictions of how PAM SAR relates to in vitro and in vivo activity. Herein, we combined site-directed mutagenesis and calcium mobilization assays with analytical pharmacology to compare modes of PAM binding, positive modulation, and agonism. We demonstrate that 3-(2-chlorophenyl)-

Indexed as

Allosteric RegulationAllosteric SiteAmino Acid SequenceCalciumCell LineCinacalcetHumansLigandsMutagenesis, Site-DirectedPhenethylaminesPropylaminesReceptors, Calcium-SensingStructure-Activity RelationshipCalciumCinacalcetLigandsN-(2-chlorophenylpropyl)-1-(3-methoxyphenyl)ethylaminePhenethylaminesPropylaminesReceptors, Calcium-Sensing

Identifiers

PMID29636377
PMCPMC5941188

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.