ArticleJournal of medicinal chemistry2013
Substituted 4-(thiazol-5-yl)-2-(phenylamino)pyrimidines are highly active CDK9 inhibitors: synthesis, X-ray crystal structures, structure-activity relationship, and anticancer activities.
Article in Journal of medicinal chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 122 citations in OpenAlex.
- Targeting the Disease Response With NlpD and LytM for Effective Nonantibiotic Treatment of Urinary Tract Infections.The Journal of infectious diseases · 2026Article
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- In silico-driven identification of potent CDK9 inhibitors through bioisosteric replacement and multi-stage virtual screening.Scientific reports · 2025Article
- Cyclin-dependent kinases as mediators of aberrant transcription in prostate cancer.Translational oncology · 2025Review
- CDK9 inhibition inhibits multiple oncogenic transcriptional and epigenetic pathways in prostate cancer.British journal of cancer · 2024Article
- Synthesis of 1,3,4-Thiadiazole Derivatives and Their Anticancer Evaluation.International journal of molecular sciences · 2023Article
- Discovery ofMolecules (Basel, Switzerland) · 2023Article
- Synthesis, Cytotoxic Evaluation, and Structure-Activity Relationship of Substituted Quinazolinones as Cyclin-Dependent Kinase 9 Inhibitors.Molecules (Basel, Switzerland) · 2022Article
- CombinedPharmaceuticals (Basel, Switzerland) · 2022Article
- CDK9 inhibitors in cancer research.RSC medicinal chemistry · 2022Review
- The Renaissance of Cyclin Dependent Kinase Inhibitors.Cancers · 2022Review
- A Molecular Modeling Approach to Identify Potential Antileishmanial Compounds Against the Cell Division Cycle (cdc)-2-Related Kinase 12 (CRK12) Receptor ofBiomolecules · 2021Article
- Development of CDK4/6 Inhibitors: A Five Years Update.Molecules (Basel, Switzerland) · 2021Review
- Selective inhibition of CDK4/6: A safe and effective strategy for developing anticancer drugs.Acta pharmaceutica Sinica. B · 2021Review
- Is Structure-Based Drug Design Ready for Selectivity Optimization?Journal of chemical information and modeling · 2020Article
- Therapeutic Targeting of the General RNA Polymerase II Transcription Machinery.International journal of molecular sciences · 2020Review
- CDKI-73 is a Novel Pharmacological Inhibitor of Rab11 Cargo Delivery and Innate Immune Secretion.Cells · 2020Article
- Article
- Targeting CDK9 for treatment of colorectal cancer.Molecular oncology · 2019Article
- CDKI-73: an orally bioavailable and highly efficacious CDK9 inhibitor against acute myeloid leukemia.Investigational new drugs · 2019Article
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
Abstract
Cancer cells often have a high demand for antiapoptotic proteins in order to resist programmed cell death. CDK9 inhibition selectively targets survival proteins and reinstates apoptosis in cancer cells. We designed a series of 4-thiazol-2-anilinopyrimidine derivatives with functional groups attached to the C5-position of the pyrimidine or to the C4-thiazol moiety and investigated their effects on CDK9 potency and selectivity. One of the most selective compounds, 12u inhibits CDK9 with IC(50) = 7 nM and shows over 80-fold selectivity for CDK9 versus CDK2. X-ray crystal structures of 12u bound to CDK9 and CDK2 provide insights into the binding modes. This work, together with crystal structures of selected inhibitors in complex with both enzymes described in a companion paper, (34) provides a rationale for the observed SAR. 12u demonstrates potent anticancer activity against primary chronic lymphocytic leukemia cells with a therapeutic window 31- and 107-fold over those of normal B- and T-cells.
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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.