Evidence map›Paper›PMID 36798313›Full record

ArticlebioRxiv : the preprint server for biology2023

A Potent and Selective CDKL5/GSK3 Chemical Probe is Neuroprotective.

Han Wee Ong, Yi Liang, William Richardson, Emily R Lowry, Carrow I Wells, Xiangrong Chen, Margaux Silvestre, Kelvin Dempster, Josie A Silvaroli, Jeffery L Smith and 6 more

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

Article in bioRxiv : the preprint server for biology, 2023. 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, 1 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 5 institutions in 3 countries.

Han Wee OngStructural Genomics Consortium, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, United States of America.
Yi LiangStructural Genomics Consortium, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, United States of America.
William RichardsonCentre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7DQ, United Kingdom.
Emily R LowryDepartment of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, 10032, United States of America; The Project ALS Therapeutics Core, Columbia University Irving Medical Center, New York, New York, 10032, United States of America.
Carrow I WellsStructural Genomics Consortium, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, United States of America.
Xiangrong ChenCentre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7DQ, United Kingdom.
Margaux SilvestreKinases and Brain Development Laboratory, The Francis Crick Institute, London, NW1 1AT, United Kingdom.
Kelvin DempsterKinases and Brain Development Laboratory, The Francis Crick Institute, London, NW1 1AT, United Kingdom.
Josie A SilvaroliDivision of Pharmaceutics and Pharmacology, College of Pharmacy and Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, 43210, United States of America.
Jeffery L SmithStructural Genomics Consortium, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, United States of America.
Hynek WichterleDepartments of Pathology and Cell Biology, Neurology, Neuroscience, Rehabilitation and Regenerative Medicine, Columbia University Irving Medical Center, New York, New York, 10032, United States of America; Center for Motor Neuron Biology and Disease, Columbia University Irving Medical Center, New York, New York, 10032, United States of America; Columbia Stem Cell Initiative, Columbia University Irving Medical Center, New York, New York, 10032, United States of America; The Project ALS Therapeutics Core, Columbia University Irving Medical Center, New York, New York, 10032, United States of America.
Navjot S PablaDivision of Pharmaceutics and Pharmacology, College of Pharmacy and Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, 43210, United States of America.
Sila K UltanirKinases and Brain Development Laboratory, The Francis Crick Institute, London, NW1 1AT, United Kingdom.
Alex N BullockCentre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7DQ, United Kingdom.
David H DrewryStructural Genomics Consortium, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, United States of America; UNC Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, United States of America.ORCID 0000-0001-5973-5798
Alison D AxtmanStructural Genomics Consortium, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, United States of America.ORCID 0000-0003-4779-9932
University of North Carolina at Chapel Hill · USDiscovery Centre · CAThe Francis Crick Institute · GBColumbia University Irving Medical Center · USThe Ohio State University · US

Funding

Illuminating Function of the Understudied Druggable KinomeU24DK116204 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI JOHNSON, GARY L. · 2017 to 2022
$13.6M
Tools for Accelerating R&D for Historically Understudied Protein KinasesR44TR001916 · NCATS · LUCEOME BIOTECHNOLOGIES, LLC · PI ZUTSHI, REENA · 2017 to 2018
$1.4M
Pilot studies to characterize CDKL5 inhibitorsR21NS112770 · NINDS · UNIVERSITY OF COLORADO DENVER · PI BENKE, TIMOTHY A · 2020 to 2020
$444k
NCATS NIH HHS R44 TR001916NIDDK NIH HHS U24 DK116204NINDS NIH HHS R21 NS112770
6 · The paper itself

Abstract

Despite mediating several essential processes in the brain, including during development, cyclin-dependent kinase-like 5 (CDKL5) remains a poorly characterized human protein kinase. Accordingly, its substrates, functions, and regulatory mechanisms have not been fully described. We realized that availability of a potent and selective small molecule probe targeting CDKL5 could enable illumination of its roles in normal development as well as in diseases where it has become aberrant due to mutation. We prepared analogs of AT-7519, a known inhibitor of several cyclin dependent and cyclin-dependent kinase-like kinases that has been advanced into Phase II clinical trials. We identified analog

Identifiers

PMID36798313
PMCPMC9934649
OpenAlexW4319937611

What Socratic holds

Textmetadata
LicenceCC BY-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 Socratic graph.