Evidence map›Paper›PMID 33550184›Full record

ArticleEuropean journal of medicinal chemistry2021

Tetrahydroindazole inhibitors of CDK2/cyclin complexes.

Jae Chul Lee, Kwon Ho Hong, Andreas Becker, Joseph S Tash, Ernst Schönbrunn, Gunda I Georg

Open access · greenAbstract 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 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.5field-weighted citation impact, top 33% 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

1 citing paper in PubMed, 9 citations in OpenAlex.

  1. Article
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

6 authors at 3 institutions in 1 country.

Jae Chul LeeDepartment of Medicinal Chemistry, Institute for Therapeutics Discovery and Development, College of Pharmacy, University of Minnesota, 717 Delaware Street, SE, Minneapolis, MN, 55455, USA.
Kwon Ho HongDepartment of Medicinal Chemistry, Institute for Therapeutics Discovery and Development, College of Pharmacy, University of Minnesota, 717 Delaware Street, SE, Minneapolis, MN, 55455, USA.
Andreas BeckerDepartment of Medicinal Chemistry, Institute for Therapeutics Discovery and Development, College of Pharmacy, University of Minnesota, 717 Delaware Street, SE, Minneapolis, MN, 55455, USA.
Joseph S TashDepartment of Molecular and Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS, 66160, USA.
Ernst SchönbrunnDrug Discovery Department, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL, 33612, USA.
Gunda I GeorgDepartment of Medicinal Chemistry, Institute for Therapeutics Discovery and Development, College of Pharmacy, University of Minnesota, 717 Delaware Street, SE, Minneapolis, MN, 55455, USA. Electronic address: georg@umn.edu.
University of Minnesota · USMoffitt Cancer Center · USUniversity of Kansas Medical Center · US

Funding

NICHD NIH HHS HHSN275200503400C
6 · The paper itself

Abstract

Over 50 tetrahydroindazoles were synthesized after 7-bromo-3,6,6-trimethyl-1-(pyridin-2-yl)-5,6,7,7a-tetrahydro-1H-indazol-4(3aH)-one (3) was identified as a hit compound in a high throughput screen for inhibition of CDK2 in complex with cyclin A. The activity of the most promising analogues was evaluated by inhibition of CDK2 enzyme complexes with various cyclins. Analogues 53 and 59 showed 3-fold better binding affinity for CDK2 and 2- to 10-fold improved inhibitory activity against CDK2/cyclin A1, E, and O compared to screening hit 3. The data from the enzyme and binding assays indicate that the binding of the analogues to a CDK2/cyclin complex is favored over binding to free CDK2. Computational analysis was used to predict a potential binding site at the CDK2/cyclin E1 interface.

Indexed as

Binding SitesCell ProliferationCyclin-Dependent Kinase 2CyclinsDose-Response Relationship, DrugEnzyme InhibitorsHumansIndazolesMCF-7 CellsMolecular StructureStructure-Activity RelationshipCDK2 protein, humanCyclin-Dependent Kinase 2CyclinsEnzyme InhibitorsIndazolesCDK2CyclinsKinase inhibitorsTetrahydroindazoles

Identifiers

PMID33550184
PMCPMC7954990
OpenAlexW3128334360

What Socratic holds

Textmetadata
LicenceTDM
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.