Evidence map›Paper›PMID 38234749›Full record

ArticlebioRxiv : the preprint server for biology2024

Small vs. Large Library Docking for Positive Allosteric Modulators of the Calcium Sensing Receptor.

Fangyu Liu, Cheng-Guo Wu, Chia-Ling Tu, Isabella Glenn, Justin Meyerowitz, Anat Levit Kaplan, Jiankun Lyu, Zhiqiang Cheng, Olga O Tarkhanova, Yurii S Moroz and 4 more

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

Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed, 4 citations in OpenAlex.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 4 institutions in 2 countries.

Fangyu LiuDept. of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco CA 94143, USA.
Cheng-Guo WuDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA, USA.
Chia-Ling TuSan Francisco VA Medical Center, Dept. of Medicine, University of California, San Francisco, San Francisco CA 94158, USA.
Isabella GlennDept. of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco CA 94143, USA.
Justin MeyerowitzDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA, USA.
Anat Levit KaplanDept. of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco CA 94143, USA.
Jiankun LyuDept. of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco CA 94143, USA.
Zhiqiang ChengSan Francisco VA Medical Center, Dept. of Medicine, University of California, San Francisco, San Francisco CA 94158, USA.
Olga O TarkhanovaChemspace LLC, Kyiv, 02094, Ukraine.
Yurii S MorozChemspace LLC, Kyiv, 02094, Ukraine.
John J IrwinDept. of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco CA 94143, USA.
Wenhan ChangSan Francisco VA Medical Center, Dept. of Medicine, University of California, San Francisco, San Francisco CA 94158, USA.
Brian K ShoichetDept. of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco CA 94143, USA.
Georgios SkiniotisDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA, USA.
University of California, San Francisco · USSan Francisco VA Medical Center · USStanford University · USMedpace (United States) · US

Funding

Development and Testing of New Computational Methods for Ligand Discovery and MechanismR35GM122481 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Brian K Shoichet · 2017 to 2026
$8.5M
A Web-Based Automatic Virtual Screening SystemR01GM071896 · NIGMS · UNIVERSITY OF TORONTO · PI IRWIN, JOHN J. · 2004 to 2024
$6.0M
Structural Basis of Signal Instigation Through Family C GPCRsR01NS122394 · NINDS · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI SKINIOTIS, GEORGIOS · 2021 to 2025
$3.4M
Mechanistic Basis of Calcium Sensing Receptor SignalingR01DK132902 · NIDDK · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI Georgios Skiniotis · 2022 to 2026
$3.1M
UCSF Core Center for Musculoskeletal Biology and MedicineP30AR066262 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MAJUMDAR, SHARMILA · 2014 to 2018
$3.0M
Vitamin D and beta-amyloid signaling in hyperparathyroidismRF1AG075742 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHANG, WENHAN, KOH, JAMES · 2023 to 2025
$2.4M
Regulation of Parathyroid Functions By G-Protein Coupled ReceptorsR01DK122259 · NIDDK · NORTHERN CALIFORNIA INSTITUTE/RES/EDU · PI CHANG, WENHAN, VILARDAGA, JEAN-PIERRE · 2019 to 2023
$2.2M
Ultra-large library docking for ligand discoveryR01GM133836 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI IRWIN, JOHN J. · 2019 to 2022
$1.6M
Regulation of parathyroid function by the amyloid precursor proteinR21AG070721 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHANG, WENHAN, KOH, JAMES · 2021 to 2022
$444k
BLRD Research Career Scientist Award ApplicationIK6BX004835 · VA · VETERANS AFFAIRS MED CTR SAN FRANCISCO · PI Wenhan Chang · 2020 to 2026
–
BCCMA: Foundational Research to Act Upon and Resist Conditions Unfavorable to Bone (FRACTURE CURB): Combined long-acting PTH and calcimimetics actions on skeletal anabolismI01BX005851 · VA · VETERANS AFFAIRS MED CTR SAN FRANCISCO · PI Wenhan Chang · 2022 to 2026
–
BLRD VA I01 BX005851BLRD VA IK6 BX004835NIAMS NIH HHS P30 AR066262NIA NIH HHS R21 AG070721NIA NIH HHS RF1 AG075742NIDDK NIH HHS R01 DK122259NIDDK NIH HHS R01 DK132902NIGMS NIH HHS R01 GM071896NIGMS NIH HHS R01 GM133836NIGMS NIH HHS R35 GM122481NINDS NIH HHS R01 NS122394
6 · The paper itself

Abstract

Drugs acting as positive allosteric modulators (PAMs) to enhance the activation of the calcium sensing receptor (CaSR) and to suppress parathyroid hormone (PTH) secretion can treat hyperparathyroidism but suffer from side effects including hypocalcemia and arrhythmias. Seeking new CaSR modulators, we docked libraries of 2.7 million and 1.2 billion molecules against transforming pockets in the active-state receptor dimer structure. Consistent with simulations suggesting that docking improves with library size, billion-molecule docking found new PAMs with a hit rate that was 2.7-fold higher than the million-molecule library and with hits up to 37-fold more potent. Structure-based optimization of ligands from both campaigns led to nanomolar leads, one of which was advanced to animal testing. This PAM displays 100-fold the potency of the standard of care, cinacalcet, in

Identifiers

PMID38234749
PMCPMC10793424
OpenAlexW4390298800

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.