ArticleJournal of medicinal chemistry2016
Rapid Discovery and Structure-Activity Relationships of Pyrazolopyrimidines That Potently Suppress Breast Cancer Cell Growth via SRC Kinase Inhibition with Exceptional Selectivity over ABL Kinase.
Article in Journal of medicinal chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 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
33 citing papers in PubMed, 69 citations in OpenAlex.
- Aromatase inhibition plus/minus Src inhibitor saracatinib (AZD0530) in advanced breast cancer therapy (ARISTACAT): a randomised phase II study.Breast cancer research and treatment · 2023Trial
- Identification of YES1 Inhibitors From Approved Drugs Using a Multimodal Deep Learning Framework.Molecular informatics · 2026Article
- Slap restricts oncogenic Src-family kinase signaling to maintain colonic epithelial homeostasis.eLife · 2026Article
- Improving the metabolic stability of a selective mTOR inhibitor through scaffold deconstruction and carbamate exploration.RSC medicinal chemistry · 2026Article
- Advances in the design and discovery of small-molecule tyrosine kinase inhibitors for breast cancer.RSC advances · 2026Review
- A Comprehensive Review of Designing and Synthetic Aspects of Pyrazolopyrimidine Derivatives as Anticancer Agents.Mini reviews in medicinal chemistry · 2026Review
- Extracellular vesicles shed by multidrug resistant cells contribute to the identification of SRC inhibitors as chemosensitizers in non-small cell lung cancer.Cancer drug resistance (Alhambra, Calif.) · 2026Article
- Curcumenol Inhibits Mast Cells Activation in Ovalbumin-Induced Anaphylaxis Model Mice through Modulation of the Fc Epsilon Receptor I Signaling Pathway.Biomolecules & therapeutics · 2025Article
- Targeting kinases that regulate programmed cell death: a new therapeutic strategy for breast cancer.Journal of translational medicine · 2025Review
- Single-cell morphological tracking of cell states to identify small-molecule modulators of liver differentiation.iScience · 2025Article
- SRC enhanced cisplatin resistance in bladder cancer by reprogramming glycolysis and pentose phosphate pathway.Communications biology · 2025Article
- Prevention of radiotherapy-induced pro-tumorigenic microenvironment by SFK inhibitors.Theranostics · 2025Article
- Discovery of pyrazolopyrimidines that selectively inhibit CSF-1R kinase by iterative design, synthesis and screening against glioblastoma cells.RSC medicinal chemistry · 2023Article
- Development of Novel Class of Phenylpyrazolo[3,4-International journal of molecular sciences · 2023Article
- Article
- Macrophages promote anti-androgen resistance in prostate cancer bone disease.The Journal of experimental medicine · 2023Article
- Coordinated activation of c-Src and FOXM1 drives tumor cell proliferation and breast cancer progression.The Journal of clinical investigation · 2023Article
- SRC kinase-mediated signaling pathways and targeted therapies in breast cancer.Breast cancer research : BCR · 2022Review
- 4-Aminopyrazolopyrimidine scaffold and its deformation in the design of tyrosine and serine/threonine kinase inhibitors in medicinal chemistry.RSC medicinal chemistry · 2022Review
- Pathway profiling of a novel SRC inhibitor, AZD0424, in combination with MEK inhibitors for cancer treatment.Molecular oncology · 2022Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
Abstract
Novel pyrazolopyrimidines displaying high potency and selectivity toward SRC family kinases have been developed by combining ligand-based design and phenotypic screening in an iterative manner. Compounds were derived from the promiscuous kinase inhibitor PP1 to search for analogs that could potentially target a broad spectrum of kinases involved in cancer. Phenotypic screening against MCF7 mammary adenocarcinoma cells generated target-agnostic structure-activity relationships that biased subsequent designs toward breast cancer treatment rather than to a particular target. This strategy led to the discovery of two potent antiproliferative leads with phenotypically distinct anticancer mode of actions. Kinase profiling and further optimization resulted in eCF506, the first small molecule with subnanomolar IC50 for SRC that requires 3 orders of magnitude greater concentration to inhibit ABL. eCF506 exhibits excellent water solubility, an optimal DMPK profile and oral bioavailability, halts SRC-associated neuromast migration in zebrafish embryos without inducing life-threatening heart defects, and inhibits SRC phosphorylation in tumor xenografts in mice.
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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.