Evidence map›Paper›PMID 40575829›Full record

ReviewCurrent opinion in nephrology and hypertension2025

Transport and thiazide-inhibition mechanisms of the Na-Cl cotransporter: a structural perspective.

Chien-Ling Lee, Liang Feng

Abstract readReview
In one paragraph

Review in Current opinion in nephrology and hypertension, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

2 authors.

Chien-Ling LeeDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California, USA.
Liang Feng

Funding

Molecular mechanisms of mitochondrial membrane transport systems in cellular energeticsR35GM153424 · NIGMS · STANFORD UNIVERSITY · PI Liang Feng · 2024 to 2026
$2.5M
NIGMS NIH HHS R35 GM153424
6 · The paper itself

Abstract

purpose of reviewThe structures of the human sodium-chloride cotransporter (hNCC) and its complex with thiazide diuretics have been determined recently. This review summarizes key structural insights into NCC's transport and inhibition mechanisms. RECENT

findingsRecent studies revealed the structures of hNCC and its complex with thiazide diuretics, in inward-facing and outward-facing conformations, respectively. The structures of hNCC in two major conformational states provided important insights into the transport and regulatory mechanisms. Thiazide-bound hNCC structures illuminated the molecular mechanisms of thiazide-mediated NCC inhibition and explained the structure-activity relationship of thiazide diuretics. SUMMARY: Structures of hNCC provide mechanistic insights into molecular mechanisms of loss-of-function NCC variants that cause Gitelman syndrome. The thiazide-bound hNCC structures provide a blueprint for further optimizing thiazide diuretics to reduce side effects. The novel interdomain interaction-mediated hNCC regulatory mechanisms revealed by structural studies lay the foundation for developing next-generation NCC modulators and NCC-rescuing therapeutics for treating NCC dysfunction.

Indexed as

Sodium Chloride Symporter InhibitorsSodium Chloride SymportersAnimalsGitelman SyndromeHumansModels, MolecularProtein ConformationStructure-Activity RelationshipThiazidesSodium Chloride Symporter InhibitorsSodium Chloride SymportersThiazidescotransportercryo-EMprotein structuressodium-chloride cotransporterthiazide diureticstransporter

Identifiers

PMID40575829
PMCPMC12337910

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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Registered trials

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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 Socratic graph.