ArticleNature communications2023
Development of allosteric and selective CDK2 inhibitors for contraception with negative cooperativity to cyclin binding.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- The non-canonical CDK2 activator SPY1 uses separable mechanisms to activate phosphorylated and unphosphorylated CDK2.The Biochemical journal · 2026Article
- Adaptive mechanisms and emerging cancer therapeutics for CDK2 inhibitors.Nature chemical biology · 2026Review
- Targeting CDKs in the RNAPII transcription cycle.Nature reviews. Drug discovery · 2026Review
- Targeting CDK-2 With Novel Indole-Pyrazole Hybrids: Discovery of Potent Anticancer Agents Supported by Mechanistic and In Silico Studies.Drug development research · 2026Article
- DT-TRAP enables accurate target recognition via simplified dosing and low-temperature incubation.Journal of pharmaceutical analysis · 2026Article
- Context-dependent synthetic lethality - an emerging precision therapeutic approach.Nature reviews. Cancer · 2026Review
- Probing Allosteric Kinase Modulators as Next Game-Changers in Fighting Neurodegeneration.Journal of medicinal chemistry · 2026Review
- Emerging Strategies to Inhibit the G1/S Transition for Cancer Therapy.Cancer research · 2026Review
- Fine-Tuning DiffDock-L for Allosteric Kinase Docking.Journal of chemical information and modeling · 2026Article
- Benchmarking all-atom biomolecular structure prediction with FoldBench.Nature communications · 2025Article
- Allosteric binding cooperativity in kinases signaling, signalopathies, and drug development.Current opinion in structural biology · 2025Review
- A Structure-Guided Kinase-Transcription Factor Interactome Atlas Reveals Docking Landscapes of the Kinome.bioRxiv : the preprint server for biology · 2025Article
- Targeting CDK2 for cancer therapy.Cell reports · 2025Review
- From cell cycle control to cancer therapy: exploring the role of CDK1 and CDK2 in tumorigenesis.Medical oncology (Northwood, London, England) · 2025Review
- Can Deep Learning Blind Docking Methods be Used to Predict Allosteric Compounds?Journal of chemical information and modeling · 2025Article
- Targeting cyclin-dependent kinase 2 (CDK2) interactions with cyclins and Speedy 1 (Spy1) for cancer and male contraception.Future medicinal chemistry · 2025Review
- Resistance mechanisms and therapeutic strategies of CDK4 and CDK6 kinase targeting in cancer.Nature cancer · 2025Review
- CDK2 Allosteric Modulators: The New Route in the Design of New Drugs as Anticancer and Non-hormonal Contraceptives.Current medicinal chemistry · 2025Review
- The value of protein allostery in rational anticancer drug design: an update.Expert opinion on drug discovery · 2024Review
- GCN2 is a determinant of the response to WEE1 kinase inhibition in small-cell lung cancer.Cell reports · 2024Article
Corrections and comments
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Authors and funding
18 authors.
Funding
Abstract
Compared to most ATP-site kinase inhibitors, small molecules that target an allosteric pocket have the potential for improved selectivity due to the often observed lower structural similarity at these distal sites. Despite their promise, relatively few examples of structurally confirmed, high-affinity allosteric kinase inhibitors exist. Cyclin-dependent kinase 2 (CDK2) is a target for many therapeutic indications, including non-hormonal contraception. However, an inhibitor against this kinase with exquisite selectivity has not reached the market because of the structural similarity between CDKs. In this paper, we describe the development and mechanism of action of type III inhibitors that bind CDK2 with nanomolar affinity. Notably, these anthranilic acid inhibitors exhibit a strong negative cooperative relationship with cyclin binding, which remains an underexplored mechanism for CDK2 inhibition. Furthermore, the binding profile of these compounds in both biophysical and cellular assays demonstrate the promise of this series for further development into a therapeutic selective for CDK2 over highly similar kinases like CDK1. The potential of these inhibitors as contraceptive agents is seen by incubation with spermatocyte chromosome spreads from mouse testicular explants, where they recapitulate Cdk2
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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.