Evidence map›Paper›PMID 32219206›Full record

ArticleACS pharmacology & translational science2018

Dual Action Calcium-Sensing Receptor Modulator Unmasks Novel Mode-Switching Mechanism.

Karen J Gregory, Irina Kufareva, Andrew N Keller, Elham Khajehali, Hee-Chang Mun, Mahvash A Goolam, Rebecca S Mason, Ben Capuano, Arthur D Conigrave, Arthur Christopoulos and 1 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in ACS pharmacology & translational science, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.8field-weighted citation impact, top 27% of its field
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

10 citing papers in PubMed, 16 citations in OpenAlex.

  1. Review
  2. The cannabinoid CBJournal of receptor and signal transduction research · 2024
    Article
  3. Calcium and Neural Stem Cell Proliferation.International journal of molecular sciences · 2024
    Review
  4. Article
  5. Cell Surface Calcium-Sensing Receptor Heterodimers: Mutant Gene Dosage Affects CaJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022
    Article
  6. Article
  7. Review
  8. Review
  9. Article
  10. Review
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

11 authors at 2 institutions in 1 country.

Karen J GregoryDrug Discovery Biology and Department of Pharmacology, Monash Institute of Pharmaceutical Sciences, 381 Royal Parade, Monash University, Parkville, Victoria 3052, Australia.
Irina KufarevaSkaggs School of Pharmacy & Pharmaceutical Sciences, University of California, 9500 Gilman Drive, La Jolla, San Diego, California MC 0747, United States.
Andrew N KellerDrug Discovery Biology and Department of Pharmacology, Monash Institute of Pharmaceutical Sciences, 381 Royal Parade, Monash University, Parkville, Victoria 3052, Australia.
Elham KhajehaliDrug Discovery Biology and Department of Pharmacology, Monash Institute of Pharmaceutical Sciences, 381 Royal Parade, Monash University, Parkville, Victoria 3052, Australia.
Hee-Chang MunSchool of Life and Environmental Sciences, Charles Perkins Centre, and Physiology and Bosch Institute, Building F13, University of Sydney, Sidney, New South Wales 2006, Australia.
Mahvash A GoolamSchool of Life and Environmental Sciences, Charles Perkins Centre, and Physiology and Bosch Institute, Building F13, University of Sydney, Sidney, New South Wales 2006, Australia.
Rebecca S MasonSchool of Life and Environmental Sciences, Charles Perkins Centre, and Physiology and Bosch Institute, Building F13, University of Sydney, Sidney, New South Wales 2006, Australia.
Ben CapuanoDrug Discovery Biology and Department of Pharmacology, Monash Institute of Pharmaceutical Sciences, 381 Royal Parade, Monash University, Parkville, Victoria 3052, Australia.
Arthur D ConigraveSchool of Life and Environmental Sciences, Charles Perkins Centre, and Physiology and Bosch Institute, Building F13, University of Sydney, Sidney, New South Wales 2006, Australia.
Arthur ChristopoulosDrug Discovery Biology and Department of Pharmacology, Monash Institute of Pharmaceutical Sciences, 381 Royal Parade, Monash University, Parkville, Victoria 3052, Australia.
Katie LeachDrug Discovery Biology and Department of Pharmacology, Monash Institute of Pharmaceutical Sciences, 381 Royal Parade, Monash University, Parkville, Victoria 3052, Australia.
Monash University · AUThe University of Sydney · AU

Funding

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
NIAID NIH HHS R01 AI118985NIGMS NIH HHS R01 GM117424
6 · The paper itself

Abstract

Negative allosteric modulators (NAMs) of the human calcium-sensing receptor (CaSR) have previously failed to show efficacy in human osteoporosis clinical trials, but there is now significant interest in repurposing these drugs for hypocalcemic disorders and inflammatory lung diseases. However, little is known about how CaSR NAMs inhibit the response to endogenous activators. An improved understanding of CaSR negative allosteric modulation may afford the opportunity to develop therapeutically superior CaSR-targeting drugs. In an attempt to elucidate the mechanistic and structural basis of allosteric modulation mediated by the previously reported NAM, calhex231, we herein demonstrate that calhex231 actually potentiates or inhibits the activity of multiple CaSR agonists depending on whether it occupies one or both protomers in a CaSR dimer. These findings reveal a novel mechanism of mode-switching at a Class C G protein-coupled receptor that has implications for drug discovery and potential clinical utility.

Identifiers

PMID32219206
PMCPMC7089027
OpenAlexW2891196885

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.