ArticleJournal of medicinal chemistry2012
Optimization of imidazo[4,5-b]pyridine-based kinase inhibitors: identification of a dual FLT3/Aurora kinase inhibitor as an orally bioavailable preclinical development candidate for the treatment of acute myeloid leukemia.
Article in Journal of medicinal chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 69 citations in OpenAlex.
- Exploration of a Novel Imidazo[4,5-b]pyridine-dihydropyrimidinone hybrids as aurora kinase a inhibitors: integrated pharmacophore modelling, docking and simulation approaches.Molecular diversity · 2026Article
- Review
- Dual-Targeting Strategy in Cancer Therapy: The Emerging Role of Pyrrolopyrimidine Scaffolds.Chemistry & biodiversity · 2026Review
- Novel sulfonamides unveiled as potent anti-lung cancer agentsRSC medicinal chemistry · 2024Article
- Reaction Pattern and Mechanistic Aspects of Iodine and Iodine-Based Reagents in Selenylation of Aliphatic, Aromatic, and (Hetero)Cyclic Systems.Topics in current chemistry (Cham) · 2024Review
- Inhibition of FLT3-ITD Kinase in Acute Myeloid Leukemia by New Imidazo[1,2-Journal of medicinal chemistry · 2023Article
- Recent Advancement in Drug Design and Discovery of Pyrazole Biomolecules as Cancer and Inflammation Therapeutics.Molecules (Basel, Switzerland) · 2022Review
- Dual Kinase Targeting in Leukemia.Cancers · 2021Review
- Quizartinib-resistant FLT3-ITD acute myeloid leukemia cells are sensitive to the FLT3-Aurora kinase inhibitor CCT241736.Blood advances · 2020Article
- Theoretical Studies Aimed at Finding FLT3 Inhibitors and a Promising Compound and Molecular Pattern with Dual Aurora B/FLT3 Activity.Molecules (Basel, Switzerland) · 2020Article
- IODVA1, a guanidinobenzimidazole derivative, targets Rac activity and Ras-driven cancer models.PloS one · 2020Article
- Metabolism of the dual FLT-3/Aurora kinase inhibitor CCT241736 in preclinical and human in vitro models: Implication for the choice of toxicology species.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2019Article
- Dual PDK1/Aurora Kinase A Inhibitors Reduce Pancreatic Cancer Cell Proliferation and Colony Formation.Cancers · 2019Article
- Privileged Structures and Polypharmacology within and between Protein Families.ACS medicinal chemistry letters · 2018Article
- Therapeutic Vulnerabilities inInternational journal of molecular sciences · 2018Article
- Rapid Construction of an Imidazo[4,5-ACS omega · 2018Article
- Aurora B prevents premature removal of spindle assembly checkpoint proteins from the kinetochore: A key role for Aurora B in mitosis.Oncotarget · 2018Article
- Synthesis and Pharmacological Activities of Pyrazole Derivatives: A Review.Molecules (Basel, Switzerland) · 2018Review
- Article
- A Simple Precursor for Highly Functionalized Fused Imidazo[4,5-b]pyridines and Imidazo[4,5-b]-1,8-naphthyridine.Molecules (Basel, Switzerland) · 2016Article
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Authors and funding
21 authors at 2 institutions in 1 country.
Funding
Abstract
Optimization of the imidazo[4,5-b]pyridine-based series of Aurora kinase inhibitors led to the identification of 6-chloro-7-(4-(4-chlorobenzyl)piperazin-1-yl)-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine (27e), a potent inhibitor of Aurora kinases (Aurora-A K(d) = 7.5 nM, Aurora-B K(d) = 48 nM), FLT3 kinase (K(d) = 6.2 nM), and FLT3 mutants including FLT3-ITD (K(d) = 38 nM) and FLT3(D835Y) (K(d) = 14 nM). FLT3-ITD causes constitutive FLT3 kinase activation and is detected in 20-35% of adults and 15% of children with acute myeloid leukemia (AML), conferring a poor prognosis in both age groups. In an in vivo setting, 27e strongly inhibited the growth of a FLT3-ITD-positive AML human tumor xenograft (MV4-11) following oral administration, with in vivo biomarker modulation and plasma free drug exposures consistent with dual FLT3 and Aurora kinase inhibition. Compound 27e, an orally bioavailable dual FLT3 and Aurora kinase inhibitor, was selected as a preclinical development candidate for the treatment of human malignancies, in particular AML, in adults and children.
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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.