ArticleACS medicinal chemistry letters2016
Discovery of Pyrazolo[1,5-a]pyrimidine TTK Inhibitors: CFI-402257 is a Potent, Selective, Bioavailable Anticancer Agent.
Article in ACS medicinal chemistry letters, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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
29 citing papers in PubMed.
- MPS1 inhibition as an anticancer strategy: where do we stand?Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2026Review
- Rewiring mitotic checkpoint control via Mps1 inhibition overcomes DNA repair-mediated resistance in glioblastoma.The Journal of biological chemistry · 2026Article
- Barrier-to-autointegration factor protects against the cGAS-STING response to chromatin bridges.PLoS genetics · 2026Article
- Targeting monopolar spindle kinase I (Mps1 or TTK) induces radiosensitization in syngeneic models of triple negative breast cancer (TNBC) and potentiates type I interferon (T1IFN) signaling.Neoplasia (New York, N.Y.) · 2025Article
- Tick-Tock: Cancer Cell Division Cycle Clocks Strike Midnight.International journal of molecular sciences · 2025Review
- Advances in pyrazolo[1,5-RSC advances · 2025Review
- Emerging opportunities to treat drug-resistant breast cancer: Discovery of novel small-molecule inhibitors against different targets.Frontiers in pharmacology · 2025Review
- Development of 2-Aminoadenine-Based Proteolysis-Targeting Chimeras (PROTACs) as Novel Potent Degraders of Monopolar Spindle 1 and Aurora Kinases.ACS pharmacology & translational science · 2024Article
- Spindle assembly checkpoint-dependent mitotic delay is required for cell division in absence of centrosomes.eLife · 2024Article
- Regioselective C(spRSC advances · 2024Article
- Small Molecule Tyrosine Kinase Inhibitors (TKIs) for Glioblastoma Treatment.International journal of molecular sciences · 2024Review
- KACS omega · 2023Article
- [Progress in the Study of Spindle Assembly Checkpoint in Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2023Article
- The cross-talk between macrophages and tumor cells as a target for cancer treatment.Frontiers in oncology · 2023Review
- High tyrosine threonine kinase expression predicts a poor prognosis: a potential therapeutic target for endometrial carcinoma.Annals of translational medicine · 2022Article
- Computational Biology Dynamics of Mps1 Kinase Molecular Interactions with Isoflavones Reveals a Chemical Scaffold with Potential to Develop New Therapeutics for the Treatment of Cancer.International journal of molecular sciences · 2022Article
- Insights into the medicinal chemistry of heterocycles integrated with a pyrazolo[1,5-RSC medicinal chemistry · 2022Review
- The spindle assembly checkpoint is a therapeutic vulnerability of CDK4/6 inhibitor-resistant ERScience advances · 2022Article
- CFI-402257, a TTK inhibitor, effectively suppresses hepatocellular carcinoma.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Cyclobutanes in Small-Molecule Drug Candidates.ChemMedChem · 2022Review
Corrections and comments
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Authors and funding
24 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
This work describes a scaffold hopping exercise that begins with known imidazo[1,2-a]pyrazines, briefly explores pyrazolo[1,5-a][1,3,5]triazines, and ultimately yields pyrazolo[1,5-a]pyrimidines as a novel class of potent TTK inhibitors. An X-ray structure of a representative compound is consistent with 1(1)/2 type inhibition and provides structural insight to aid subsequent optimization of in vitro activity and physicochemical and pharmacokinetic properties. Incorporation of polar moieties in the hydrophobic and solvent accessible regions modulates physicochemical properties while maintaining potency. Compounds with enhanced oral exposure were identified for xenograft studies. The work culminates in the identification of a potent (TTK K i = 0.1 nM), highly selective, orally bioavailable anticancer agent (CFI-402257) for IND enabling studies.
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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.