Evidence map›Paper›PMID 33092904›Full record

ArticleEuropean journal of medicinal chemistry2021

1-BENZYLSPIRO[PIPERIDINE-4,1'-PYRIDO[3,4-b]indole] 'co-potentiators' for minimal function CFTR mutants.

Jung-Ho Son, Puay-Wah Phuan, Jie S Zhu, Elena Lipman, Amy Cheung, Ka Yi Tsui, Dean J Tantillo, Alan S Verkman, Peter M Haggie, Mark J Kurth

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in European journal of medicinal chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Review
  5. 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

10 authors.

Jung-Ho SonDepartment of Chemistry, University of California, Davis, CA, 95616, USA.
Puay-Wah PhuanDepartments of Medicine & Physiology, University of California San Francisco, CA 94143, USA.
Jie S ZhuDepartment of Chemistry, University of California, Davis, CA, 95616, USA.
Elena LipmanDepartment of Chemistry, University of California, Davis, CA, 95616, USA.
Amy CheungDepartment of Chemistry, University of California, Davis, CA, 95616, USA.
Ka Yi TsuiDepartment of Chemistry, University of California, Davis, CA, 95616, USA.
Dean J TantilloDepartment of Chemistry, University of California, Davis, CA, 95616, USA.
Alan S VerkmanDepartments of Medicine & Physiology, University of California San Francisco, CA 94143, USA.
Peter M HaggieDepartments of Medicine & Physiology, University of California San Francisco, CA 94143, USA. Electronic address: peter.haggie@ucsf.edu.
Mark J KurthDepartment of Chemistry, University of California, Davis, CA, 95616, USA. Electronic address: mjkurth@ucdavis.edu.

Funding

SynthesisP30DK072517 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VERKMAN, ALAN S · 2005 to 2022
$18.1M
Translational Approaches to Develop Drug Therapy for DiarrheaR24DK099803 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI DONOWITZ, MARK · 2014 to 2019
$8.9M
Functional Role of Aquaporins in Eye PhysiologyR01EY013574 · NEI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VERKMAN, ALAN S · 2002 to 2022
$7.6M
Correction of defective functional expression of CFTR in cystic fibrosisR01DK075302 · NIDDK · MCGILL UNIVERSITY · PI LUKACS, GERGELY L. · 2006 to 2020
$3.3M
NEI NIH HHS R01 EY013574NIDDK NIH HHS P30 DK072517NIDDK NIH HHS R01 DK075302NIDDK NIH HHS R24 DK099803
6 · The paper itself

Abstract

We previously identified a spiro [piperidine-4,1-pyrido [3,4-b]indole] class of co-potentiators that function in synergy with existing CFTR potentiators such as VX-770 or GLGP1837 to restore channel activity of a defined subset of minimal function cystic fibrosis transmembrane conductance regulator (CFTR) mutants. Here, structure-activity studies were conducted to improve their potency over the previously identified compound, 20 (originally termed CP-A01). Targeted synthesis of 37 spiro [piperidine-4,1-pyrido [3,4-b]indoles] was generally accomplished using versatile two or three step reaction protocols with each step having high efficiency. Structure-activity relationship studies established that analog 2i, with 6'-methoxyindole and 2,4,5-trifluorobenzyl substituents, had the greatest potency for activation of N1303K-CFTR, with EC

Indexed as

AminophenolsAnimalsCell LineChloride Channel AgonistsCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorHumansIndolesModels, MolecularMutationPiperidinesQuinolonesRatsStructure-Activity RelationshipAminophenolsChloride Channel AgonistsCystic Fibrosis Transmembrane Conductance RegulatorIndolesivacaftorPiperidinesQuinolonesc.3700A>GCFTRCystic fibrosisModulatorN1303K-CFTRPotentiator

Identifiers

PMID33092904
PMCPMC7744356

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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 OpenQuestion graph.