Evidence map›Paper›PMID 39004018›Full record

ArticleEuropean journal of medicinal chemistry2024

Discovery of bivalent small molecule degraders of cyclin-dependent kinase 7 (CDK7).

Wenzhi Ji, Guangyan Du, Jie Jiang, Wenchao Lu, Caitlin E Mills, Linjie Yuan, Fen Jiang, Zhixiang He, Gary A Bradshaw, Mirra Chung and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in European journal of medicinal chemistry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Review
  2. Review
  3. Targeting CDKs in the RNAPII transcription cycle.Nature reviews. Drug discovery · 2026
    Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. 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

15 authors.

Wenzhi JiDepartment of Chemical and Systems Biology, Chem-H, and Stanford Cancer Institute, Stanford School of Medicine, Stanford University, Stanford, CA, 94305, USA.
Guangyan DuDepartment of Cancer Biology, Dana-Farber Cancer Institute, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, 02115, USA.
Jie JiangDepartment of Cancer Biology, Dana-Farber Cancer Institute, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, 02115, USA.
Wenchao LuDepartment of Chemical and Systems Biology, Chem-H, and Stanford Cancer Institute, Stanford School of Medicine, Stanford University, Stanford, CA, 94305, USA.
Caitlin E MillsLaboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School, Boston, MA, 02115, USA.
Linjie YuanDepartment of Chemical and Systems Biology, Chem-H, and Stanford Cancer Institute, Stanford School of Medicine, Stanford University, Stanford, CA, 94305, USA.
Fen JiangDepartment of Chemical and Systems Biology, Chem-H, and Stanford Cancer Institute, Stanford School of Medicine, Stanford University, Stanford, CA, 94305, USA.
Zhixiang HeDepartment of Cancer Biology, Dana-Farber Cancer Institute, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, 02115, USA.
Gary A BradshawLaboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School, Boston, MA, 02115, USA.
Mirra ChungLaboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School, Boston, MA, 02115, USA.
Zixuan JiangDepartment of Chemical and Systems Biology, Chem-H, and Stanford Cancer Institute, Stanford School of Medicine, Stanford University, Stanford, CA, 94305, USA.
Woong Sub ByunDepartment of Chemical and Systems Biology, Chem-H, and Stanford Cancer Institute, Stanford School of Medicine, Stanford University, Stanford, CA, 94305, USA.
Stephen M HinshawDepartment of Chemical and Systems Biology, Chem-H, and Stanford Cancer Institute, Stanford School of Medicine, Stanford University, Stanford, CA, 94305, USA.
Tinghu ZhangDepartment of Chemical and Systems Biology, Chem-H, and Stanford Cancer Institute, Stanford School of Medicine, Stanford University, Stanford, CA, 94305, USA. Electronic address: ztinghu8@stanford.edu.
Nathanael S GrayDepartment of Chemical and Systems Biology, Chem-H, and Stanford Cancer Institute, Stanford School of Medicine, Stanford University, Stanford, CA, 94305, USA. Electronic address: nsgray01@stanford.edu.

Funding

Degrading therapeutically important kinases using small moleculesR01CA218278 · NCI · STANFORD UNIVERSITY · PI Eric Sebastian Fischer, NATHANAEL Schiander GRAY · 2019 to 2026
$4.6M
Targeting CDK7 in CCNE1-amplified Ovarian CancerR01CA258553 · NCI · STANFORD UNIVERSITY · PI NATHANAEL Schiander GRAY, Panagiotis Konstantinopoulos · 2022 to 2026
$3.5M
Development and Application of Selective Covalent Cdk7 InhibitorsR01CA179483 · NCI · DANA-FARBER CANCER INST · PI GRAY, NATHANAEL SCHIANDER, MITSIADES, CONSTANTINE S. · 2014 to 2016
$1.5M
NCI NIH HHS R01 CA179483NCI NIH HHS R01 CA218278NCI NIH HHS R01 CA258553
6 · The paper itself

Abstract

Cyclin-dependent kinase 7, along with cyclin H and MAT1, forms the CDK-activating complex (CAK), which directs cell cycle progression via T-loop phosphorylation of cell cycle CDKs. Pharmacological inhibition of CDK7 leads to selective anti-cancer effects in cellular and in vivo models, motivating several ongoing clinical investigations of this target. Current CDK7 inhibitors are either reversible or covalent inhibitors of its catalytic activity. We hypothesized that small molecule targeted protein degradation (TPD) might result in differentiated pharmacology due to the loss of scaffolding functions. Here, we report the design and characterization of a potent CDK7 degrader that is comprised of an ATP-competitive CDK7 binder linked to a CRL2

Indexed as

Cell ProliferationCyclin-Dependent KinasesProtein Kinase InhibitorsAnimalsAntineoplastic AgentsCell Line, TumorCyclin-Dependent Kinase-Activating KinaseDose-Response Relationship, DrugDrug DiscoveryDrug Screening Assays, AntitumorHumansMiceMolecular StructureProteolysisSmall Molecule LibrariesStructure-Activity RelationshipAntineoplastic AgentsCDK7 protein, humanCyclin-Dependent Kinase-Activating KinaseCyclin-Dependent KinasesProtein Kinase InhibitorsSmall Molecule LibrariesCDK7PROTACProtein degraderSelective

Identifiers

PMID39004018
PMCPMC11316633

What OpenQuestion holds

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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.