Evidence map›Paper›PMID 42358219›Full record

ArticleJournal of the American Chemical Society2026

A Type II CDK6 Degrader Enables Cellular Targeting beyond the Limits of Type II Inhibition.

Ji Hyeon Kim, Caitlin E Mills, Zuzanna Kozicka, Daniel C Scott, Cyrus Jin, Zixuan Jiang, Brendan G Dwyer, Qixiang Geng, Sean T Toenjes, Woong Sub Byun and 12 more

Abstract read
In one paragraph

Article in Journal of the American Chemical Society, 2026. 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.

No citing paper in PubMed yet.

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

22 authors.

Ji Hyeon KimDepartment of Chemical and Systems Biology, ChEM-H, and Stanford Cancer Institute, Stanford School of Medicine, Stanford University, Stanford, California 94305, United States.
Caitlin E MillsLaboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, United States.
Zuzanna KozickaDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, United States.
Daniel C ScottDepartment of Structural Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, United States.
Cyrus JinDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, United States.
Zixuan JiangDepartment of Chemical and Systems Biology, ChEM-H, and Stanford Cancer Institute, Stanford School of Medicine, Stanford University, Stanford, California 94305, United States.
Brendan G DwyerDepartment of Chemical and Systems Biology, ChEM-H, and Stanford Cancer Institute, Stanford School of Medicine, Stanford University, Stanford, California 94305, United States.ORCID 0000-0001-8593-4184
Qixiang GengDepartment of Chemical and Systems Biology, ChEM-H, and Stanford Cancer Institute, Stanford School of Medicine, Stanford University, Stanford, California 94305, United States.
Sean T ToenjesDepartment of Chemical and Systems Biology, ChEM-H, and Stanford Cancer Institute, Stanford School of Medicine, Stanford University, Stanford, California 94305, United States.ORCID 0000-0001-8782-3023
Woong Sub ByunDepartment of Chemical and Systems Biology, ChEM-H, and Stanford Cancer Institute, Stanford School of Medicine, Stanford University, Stanford, California 94305, United States.ORCID 0000-0003-4676-3698
Dina ElHarouniDepartment of Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, United States.
Hongyu LiDepartment of Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, United States.
Keith L LigonDepartment of Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, United States.
Abby M ThornhillDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, United States.
Hannah M JonesDepartment of Chemical and Systems Biology, ChEM-H, and Stanford Cancer Institute, Stanford School of Medicine, Stanford University, Stanford, California 94305, United States.
Bryan A RomeroDepartment of Chemical and Systems Biology, ChEM-H, and Stanford Cancer Institute, Stanford School of Medicine, Stanford University, Stanford, California 94305, United States.
Stephen M HinshawDepartment of Chemical and Systems Biology, ChEM-H, and Stanford Cancer Institute, Stanford School of Medicine, Stanford University, Stanford, California 94305, United States.ORCID 0000-0003-4215-5206
Benjamin L EbertDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, United States.
Brenda A SchulmanDepartment of Structural Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, United States.
Katherine A DonovanDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, United States.ORCID 0000-0002-8539-5106
Eric S FischerDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, United States.ORCID 0000-0001-7337-6306
Nathanael S GrayDepartment of Chemical and Systems Biology, ChEM-H, and Stanford Cancer Institute, Stanford School of Medicine, Stanford University, Stanford, California 94305, United States.ORCID 0000-0001-5354-7403

Funding

TYROSINE KINASE ONCOGENESIS IN MYELOID LEUKEMIAP01CA066996 · NCI · DANA-FARBER CANCER INSTITUTE · PI SCOTT A ARMSTRONG · 1996 to 2026
$52.5M
Degrading therapeutically important kinases using small moleculesR01CA218278 · NCI · STANFORD UNIVERSITY · PI Eric Sebastian Fischer, NATHANAEL Schiander GRAY · 2019 to 2026
$4.6M
The molecular basis of IMiD induced neo-substrate recruitment to the CRL4CRBN ubiquitin E3 ligase.R01CA214608 · NCI · DANA-FARBER CANCER INST · PI Eric Sebastian Fischer · 2017 to 2026
$4.0M
Development of a generalizable chemo-proteomics screening platform for small molecule degraders applied to HDACsR01CA262188 · NCI · DANA-FARBER CANCER INST · PI FISCHER, ERIC SEBASTIAN · 2022 to 2025
$1.8M
500 MHz NMR Spectrometer System with High Sensitivity Cryoprobe and Automated Sample Changer for Biochemical ResearchS10OD028697 · OD · STANFORD UNIVERSITY · PI BURNS, NOAH ZACHARY · 2020 to 2020
$709k
NCI NIH HHS P01 CA066996NCI NIH HHS R01 CA214608NCI NIH HHS R01 CA218278NCI NIH HHS R01 CA262188NIH HHS S10 OD028697
6 · The paper itself

Abstract

PROTACs are commonly developed by linking E3 ligase-recruiting ligands to established inhibitors of a protein target, often resulting in degraders that retain enzymatic inhibition. Type II inhibition of cyclin-dependent kinases (CDKs) has been challenging, as reported compounds generally exhibit weak biochemical potency and limited cellular activity. Consistent with these limitations, most reported CDK degraders have been derived from type I ATP-competitive inhibitors. Here, we explored whether targeted protein degradation could enable functional CDK targeting from a type II kinase scaffold. Using the multikinase inhibitor regorafenib as a starting scaffold, we generated a focused library of CRL4

Indexed as

Cyclin-Dependent Kinase 6Protein Kinase InhibitorsHumansProteolysisProteolysis Targeting ChimeraCDK6 protein, humanCyclin-Dependent Kinase 6Protein Kinase InhibitorsProteolysis Targeting Chimera

Identifiers

PMID42358219
PMCPMC13352627

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.