Evidence map›Paper›PMID 35597007›Full record

ArticleEuropean journal of medicinal chemistry2022

Synthesis and Structure-Activity relationships of cyclin-dependent kinase 11 inhibitors based on a diaminothiazole scaffold.

Zhengnian Li, Ryosuke Ishida, Yan Liu, Jinhua Wang, Yina Li, Yang Gao, Jie Jiang, Jianwei Che, Jason M Sheltzer, Matthew B Robers and 4 more

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

Article in European journal of medicinal chemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.7field-weighted citation impact, top 29% 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

6 citing papers in PubMed, 9 citations in OpenAlex.

  1. Review
  2. Targeting CDKs in the RNAPII transcription cycle.Nature reviews. Drug discovery · 2026
    Review
  3. Article
  4. Article
  5. Article
  6. 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

14 authors at 7 institutions in 1 country.

Zhengnian LiChemical and Systems Biology, Chem-H, Stanford Cancer Institute, Stanford Medicine, Stanford University, Stanford, CA, USA.
Ryosuke IshidaChemical and Systems Biology, Chem-H, Stanford Cancer Institute, Stanford Medicine, Stanford University, Stanford, CA, USA.
Yan LiuDepartment of Biochemistry, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA; Department of Radiation Oncology, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA.
Jinhua WangDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.
Yina LiDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.
Yang GaoDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.
Jie JiangDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.
Jianwei CheDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.
Jason M SheltzerYale University School of Medicine, New Haven, CT, USA.
Matthew B RobersPromega Corporation, Madison, WI, USA.
Tinghu ZhangChemical and Systems Biology, Chem-H, Stanford Cancer Institute, Stanford Medicine, Stanford University, Stanford, CA, USA.
Kenneth D WestoverDepartment of Biochemistry, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA; Department of Radiation Oncology, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA.
Behnam NabetHuman Biology Division, Fred Hutchinson Cancer Center, Seattle, WA, USA. Electronic address: bnabet@fredhutch.org.
Nathanael S GrayChemical and Systems Biology, Chem-H, Stanford Cancer Institute, Stanford Medicine, Stanford University, Stanford, CA, USA. Electronic address: nsgray01@stanford.edu.
Stanford University · USHarvard University · USDana-Farber Cancer Institute · USThe University of Texas Southwestern Medical Center · USFred Hutch Cancer Center · USPromega (United States) · USYale University · US

Funding

Targeted disruption of the YAP/TAZ/TEAD axis in pancreatic cancerK22CA258805 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI NABET, BEHNAM · 2021 to 2024
$644k
NCI NIH HHS K22 CA258805
6 · The paper itself

Abstract

Cyclin-dependent kinases (CDK) are attractive targets for drug discovery due to their wide range of cellular functions. CDK11 is an understudied CDK with roles in transcription and splicing, cell cycle regulation, neuronal function, and apoptosis. In this study, we describe a medicinal chemistry campaign to identify a CDK11 inhibitor. Employing a promising but nonselective CDK11-targeting scaffold (JWD-047), extensive structure-guided medicinal chemistry modifications led to the identification of ZNL-05-044. A combination of biochemical evaluations and NanoBRET cellular assays for target engagement guided the SAR towards a 2,4-diaminothiazoles CDK11 probe with significantly improved kinome-wide selectivity over JWD-047. CDK11 inhibition with ZNL-05-044 leads to G2/M cell cycle arrest, consistent with prior work evaluating OTS964, and impacts CDK11-dependent mRNA splicing in cells. Together, ZNL-05-044 serves as a tool compound for further optimization and interrogation of the consequences of CDK11 inhibition.

Indexed as

ApoptosisCyclin-Dependent KinasesCell Cycle CheckpointsCyclin-Dependent Kinase 2Structure-Activity RelationshipCyclin-Dependent Kinase 2Cyclin-Dependent KinasesCDK11Kinase inhibitorSerine/threonine protein kinaseStructure-activity relationship

Identifiers

PMID35597007
PMCPMC9477540
OpenAlexW4229365958

What OpenQuestion 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 OpenQuestion graph.