ArticleNature chemical biology2021
Discovery and resistance mechanism of a selective CDK12 degrader.
Article in Nature chemical biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
What it found
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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.
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.
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Who cites it
74 citing papers in PubMed, 133 citations in OpenAlex.
- Super-enhancer landscape regulated by CDK12 drives retinoblastoma progression.British journal of cancer · 2026Article
- Advancing PROTAC therapeutics through chemistry-guided design of smart delivery systems.Acta pharmacologica Sinica · 2026Review
- CDK7, CDK9, or CDK11 inhibition reduces neutrophil-driven inflammation and tissue damage in experimental autoimmune models.Cell communication and signaling : CCS · 2026Article
- Cyclins and Cyclin-Dependent Kinases: Structure, Biological Functions, and Innovative Targeting Strategies in Cancer.MedComm · 2026Review
- Targeting CDKs in the RNAPII transcription cycle.Nature reviews. Drug discovery · 2026Review
- Pan-cancer multi-omics characterization of CDK12 and virtual screening of Vietnamese natural products for novel inhibitors.Molecular diversity · 2026Article
- Inhibition of cyclin-dependent kinases 12/13 using CT7439 as a treatment for colorectal cancer with CDK12 upregulation.Molecular oncology · 2026Article
- Development of PROTACs for targeted degradation of oncogenic TRK fusions.RSC chemical biology · 2026Article
- Research Progress of PROTACs in Breast Cancer: Subtype-Oriented Target Landscape, Clinical Stratification Evidence, and Engineering Strategies for Translation.Biomedicines · 2026Review
- Inactivation of CDK12 Enhances Mitochondrial Efficiency to Suppress DNA Damage.Journal of cellular and molecular medicine · 2026Article
- Induced proximity-based therapeutic modalities.Nature reviews. Drug discovery · 2026Review
- Exploring imidazo[1,2-a]pyridine hybrids in cancer therapy: ADMET profiling, molecular docking, MD simulations and DFT calculations.Scientific reports · 2026Article
- A Novel Paradigm for Targeting Challenging Targets: Advancing Technologies and Future Directions of Molecular Glue Degraders.Molecules (Basel, Switzerland) · 2026Review
- CDK12 and CDK13 in oncology: from RNA regulation to therapeutic targeting.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Recent advances in targeting protein degradation for tumor immunotherapy.Journal of hematology & oncology · 2025Review
- A functional map of CDK-drug interactions at single amino acid resolution.bioRxiv : the preprint server for biology · 2025Article
- Review
- Rational Design of CDK12/13 and BRD4 Molecular Glue Degraders.Angewandte Chemie (International ed. in English) · 2025Article
- Advancing Design Strategy of PROTACs for Cancer Therapy.MedComm · 2025Review
- Targeted protein degradation for cancer therapy.Nature reviews. Cancer · 2025Review
14 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
Cyclin-dependent kinase 12 (CDK12) is an emerging therapeutic target due to its role in regulating transcription of DNA-damage response (DDR) genes. However, development of selective small molecules targeting CDK12 has been challenging due to the high degree of homology between kinase domains of CDK12 and other transcriptional CDKs, most notably CDK13. In the present study, we report the rational design and characterization of a CDK12-specific degrader, BSJ-4-116. BSJ-4-116 selectively degraded CDK12 as assessed through quantitative proteomics. Selective degradation of CDK12 resulted in premature cleavage and poly(adenylation) of DDR genes. Moreover, BSJ-4-116 exhibited potent antiproliferative effects, alone and in combination with the poly(ADP-ribose) polymerase inhibitor olaparib, as well as when used as a single agent against cell lines resistant to covalent CDK12 inhibitors. Two point mutations in CDK12 were identified that confer resistance to BSJ-4-116, demonstrating a potential mechanism that tumor cells can use to evade bivalent degrader molecules.
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What OpenQuestion holds
Registered trials
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.