ArticleBritish journal of cancer2016
Combined PI3K and CDK2 inhibition induces cell death and enhances in vivo antitumour activity in colorectal cancer.
Article in British journal of cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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.
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.
Who cites it
30 citing papers in PubMed, 57 citations in OpenAlex.
- 7-azaindole as privileged scaffold: Advances in drug design and structural modification.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Review
- Learning drug synergy through environment-conditioned feature modulation.Bioinformatics (Oxford, England) · 2026Article
- Drug Discovery Applications of Nitroso (Hetero)Arene Derivatives.ChemPlusChem · 2025Review
- From cell cycle control to cancer therapy: exploring the role of CDK1 and CDK2 in tumorigenesis.Medical oncology (Northwood, London, England) · 2025Review
- Uncovering Anti-Melanoma Mechanisms ofInternational journal of molecular sciences · 2025Article
- Structure-guided identification of mitogen-activated protein kinase-1 inhibitors towards anticancer therapeutics.PloS one · 2025Article
- Extracellular vesicle-mediated delivery of miR-766-3p from bone marrow stromal cells as a therapeutic strategy against colorectal cancer.Cancer cell international · 2024Article
- MYBL2 Drives Prostate Cancer Plasticity: Inhibiting Its Transcriptional Target CDK2 for RB1-Deficient Neuroendocrine Prostate Cancer.Cancer research communications · 2024Article
- New spiro-indeno[1,2-Journal of enzyme inhibition and medicinal chemistry · 2023Article
- Discovery ofMolecules (Basel, Switzerland) · 2023Article
- Identification of a novel MYC target gene set signature for predicting the prognosis of osteosarcoma patients.Frontiers in oncology · 2023Article
- Up-regulation of the PI3K/AKT and RHO/RAC/PAK signalling pathways in CHK1 inhibitor resistant Eµ-Myc lymphoma cells.The Biochemical journal · 2022Article
- Cell line models for drug discovery in PIK3CA-mutated colorectal cancers.Medical oncology (Northwood, London, England) · 2022Article
- Targeting cell-cycle machinery in cancer.Cancer cell · 2021Review
- Cyclin-Dependent Kinases (CDK) and Their Role in Diseases Development-Review.International journal of molecular sciences · 2021Review
- Article
- CCNE1 Amplification as a Predictive Biomarker of Chemotherapy Resistance in Epithelial Ovarian Cancer.Diagnostics (Basel, Switzerland) · 2020Review
- Identification of High-Affinity Inhibitors of Cyclin-Dependent Kinase 2 Towards Anticancer Therapy.Molecules (Basel, Switzerland) · 2019Article
- An increased cell cycle gene network determines MEK and Akt inhibitor double resistance in triple-negative breast cancer.Scientific reports · 2019Article
- Therapeutic Potency of PI3K Pharmacological Inhibitors of Gastrointestinal Cancer.Middle East journal of digestive diseases · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe phosphatidylinositol-3-kinase/mammalian target of rapamycin (PI3K/mTOR) pathway is commonly deregulated in human cancer, hence many PI3K and mTOR inhibitors have been developed and have now reached clinical trials. Similarly, CDKs have been investigated as cancer drug targets.
methodsWe have synthesised and characterised a series of 6-aminopyrimidines identified from a kinase screen that inhibit PI3K and/or mTOR and/or CDK2. Kinase inhibition, tumour cell growth, cell cycle distribution, cytotoxicity and signalling experiments were undertaken in HCT116 and HT29 colorectal cancer cell lines, and in vivo HT29 efficacy studies.
results2,6-Diaminopyrimidines with an O(4)-cyclohexylmethyl substituent and a C-5-nitroso or cyano group (1,2,5) induced cell cycle phase alterations and were growth inhibitory (GI50<20 μM). Compound 1, but not 2 or 5, potently inhibits CDK2 (IC50=0.1 nM) as well as PI3K, and was cytotoxic at growth inhibitory concentrations. Consistent with kinase inhibition data, compound 1 reduced phospho-Rb and phospho-rS6 at GI50 concentrations. Combination of NU6102 (CDK2 inhibitor) and pictilisib (GDC-0941; pan-PI3K inhibitor) resulted in synergistic growth inhibition, and enhanced cytotoxicity in HT29 cells in vitro and HT29 tumour growth inhibition in vivo.
conclusionsThese studies identified a novel series of mixed CDK2/PI3K inhibitors and demonstrate that dual targeting of CDK2 and PI3K can result in enhanced antitumour activity.
Indexed as
Identifiers
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.