Evidence map›Paper›PMID 33278061›Full record

ArticleChemMedChem2021

The tale of proteolysis targeting chimeras (PROTACs) for Leucine-Rich Repeat Kinase 2 (LRRK2).

Markella Konstantinidou, Asmaa Oun, Pragya Pathak, Bidong Zhang, Zefeng Wang, Frans Ter Brake, Amalia M Dolga, Arjan Kortholt, Alexander Dömling

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

Article in ChemMedChem, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.3field-weighted citation impact, top 11% 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

15 citing papers in PubMed, 41 citations in OpenAlex.

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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

9 authors at 2 institutions in 2 countries.

Markella KonstantinidouDepartment of Pharmacy, Group of Drug Design, University of Groningen, A. Deusinglaan 1, 9713 AV, Groningen, The Netherlands.
Asmaa OunDepartment of Molecular Pharmacology, Groningen Research Institute of Pharmacy (GRIP), University of Groningen, A. Deusinglaan 1, 9713 AV, Groningen, The Netherlands.
Pragya PathakDepartment of Cell Biochemistry, Groningen Institute of Biomolecular Sciences & Biotechnology, University of Groningen, Nijenborgh 7, 9747 AG, Groningen, The Netherlands.
Bidong ZhangDepartment of Pharmacy, Group of Drug Design, University of Groningen, A. Deusinglaan 1, 9713 AV, Groningen, The Netherlands.
Zefeng WangDepartment of Pharmacy, Group of Drug Design, University of Groningen, A. Deusinglaan 1, 9713 AV, Groningen, The Netherlands.
Frans Ter BrakeDepartment of Pharmacy, Group of Drug Design, University of Groningen, A. Deusinglaan 1, 9713 AV, Groningen, The Netherlands.
Amalia M DolgaDepartment of Molecular Pharmacology, Groningen Research Institute of Pharmacy (GRIP), University of Groningen, A. Deusinglaan 1, 9713 AV, Groningen, The Netherlands.
Arjan KortholtDepartment of Cell Biochemistry, Groningen Institute of Biomolecular Sciences & Biotechnology, University of Groningen, Nijenborgh 7, 9747 AG, Groningen, The Netherlands.
Alexander DömlingDepartment of Pharmacy, Group of Drug Design, University of Groningen, A. Deusinglaan 1, 9713 AV, Groningen, The Netherlands.
University of Groningen · NLSüleyman Demirel University · TR

Funding

Real-time discovery of inhibitors among billion compounds for preview and downloadR01GM097082 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CAMACHO, CARLOS J. · 2011 to 2020
$2.5M
Accelerated Early stage drug dIScovery 675555COFUNDs ALERT 665250European Lead Factory 115489KWF Kankerbestrijding 10504NIGMS NIH HHS R01 GM097082NIH HHS 2R01 GM097082-05Prominent 754425Qatar National Research Foundation NPRP6-065-3-012
6 · The paper itself

Abstract

Here we present the rational design and synthetic methodologies towards proteolysis-targeting chimeras (PROTACs) for the recently-emerged target leucine-rich repeat kinase 2 (LRRK2). Two highly potent, selective, brain-penetrating kinase inhibitors were selected, and their structure was appropriately modified to assemble a cereblon-targeting PROTAC. Biological data show strong kinase inhibition and the ability of the synthesized compounds to enter the cells. However, data regarding the degradation of the target protein are inconclusive. The reasons for the inefficient degradation of the target are further discussed.

Indexed as

HEK293 CellsHumansLeucine-Rich Repeat Serine-Threonine Protein Kinase-2Molecular StructureProtein Kinase InhibitorsProteolysisPyrimidinesPyrroles3-(4-(morpholin-4-yl)-7H-pyrrolo(2,3-d)pyrimidin-5-yl)benzonitrileLeucine-Rich Repeat Serine-Threonine Protein Kinase-2LRRK2 protein, humanProtein Kinase InhibitorsPyrimidinesPyrrolescereblondegradationLRRK2Parkinson's diseasePROTAC

Identifiers

PMID33278061
PMCPMC8048960
OpenAlexW3110485539

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.