ArticleJournal of medicinal chemistry2010
A type-II kinase inhibitor capable of inhibiting the T315I "gatekeeper" mutant of Bcr-Abl.
Article in Journal of medicinal chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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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
27 citing papers in PubMed, 73 citations in OpenAlex.
- Counter-Therapeutic Strategies for Resistance of FLT3 Inhibitors in Acute Myeloid Leukemia.Cells · 2025Review
- The Kinase Inhibitor GNF-7 Is Synthetically Lethal in Topoisomerase 1-Deficient Ewing Sarcoma.Cancers · 2025Article
- Comprehensive study of imidazole-based hydrazones: From design, synthesis, and characterization to in vitro and in silico antiproliferative activity analysis.Turkish journal of chemistry · 2025Article
- Screening and identification of host signaling pathways for alleviating influenza-induced production of pro-inflammatory cytokines, IP-10, IL-8, and MCP-1, using a U937 cell-based influenza model.Frontiers in microbiology · 2025Article
- SH2 domain protein E and ABL signaling regulate blood vessel size.PLoS genetics · 2024Article
- The Progress of Small Molecule Targeting BCR-ABL in the Treatment of Chronic Myeloid Leukemia.Mini reviews in medicinal chemistry · 2024Review
- GNF-7, a novel FLT3 inhibitor, overcomes drug resistance for the treatment of FLT3‑ITD acute myeloid leukemia.Cancer cell international · 2023Article
- Review
- Discovery of New Quinolone-Based Diarylamides as Potent B-RAFInternational journal of molecular sciences · 2023Article
- Identification of highly selective type II kinase inhibitors with chiral peptidomimetic tails.Journal of enzyme inhibition and medicinal chemistry · 2022Article
- Migrating to Long-Read Sequencing for Clinical RoutineCancer informatics · 2022Article
- Chemical Reactivity and Optical and Pharmacokinetics Studies of 14 Multikinase Inhibitors and Their Docking Interactions Toward ACK1 for Precision Oncology.Frontiers in chemistry · 2022Article
- Novel and Potent Small Molecules against Melanoma Harboring BRAF Class I/II/III Mutants for Overcoming Drug Resistance.International journal of molecular sciences · 2021Article
- Novel Small Molecules Capable of Blocking mtRAS-Signaling Pathway.Frontiers in oncology · 2021Article
- Ponatinib Protects Mice From Lethal Influenza Infection by Suppressing Cytokine Storm.Frontiers in immunology · 2019Article
- EnABLing Tumor Growth and Progression: Recent progress in unraveling the functions of ABL kinases in solid tumor cells.Current pharmacology reports · 2018Article
- Quantitative, Wide-Spectrum Kinase Profiling in Live Cells for Assessing the Effect of Cellular ATP on Target Engagement.Cell chemical biology · 2018Article
- Synthesis and identification of GZD856 as an orally bioavailable Bcr-AblJournal of enzyme inhibition and medicinal chemistry · 2017Article
- Molecular modeling study of the induced-fit effect on kinase inhibition: the case of fibroblast growth factor receptor 3 (FGFR3).Journal of computer-aided molecular design · 2015Article
- Article
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 3 countries.
Funding
Abstract
The second generation of Bcr-Abl inhibitors nilotinib, dasatinib, and bosutinib developed to override imatinib resistance are not active against the T315I "gatekeeper" mutation. Here we describe a type-II T315I inhibitor 2 (GNF-7), based upon a 3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one scaffold which is capable of potently inhibiting wild-type and T315I Bcr-Abl as well as other clinically relevant Bcr-Abl mutants such as G250E, Q252H, Y253H, E255K, E255V, F317L, and M351T in biochemical and cellular assays. In addition, compound 2 displayed significant in vivo efficacy against T315I-Bcr-Abl without appreciable toxicity in a bioluminescent xenograft mouse model using a transformed T315I-Bcr-Abl-Ba/F3 cell line that has a stable luciferase expression. Compound 2 is among the first type-II inhibitors capable of inhibiting T315I to be described and will serve as a valuable lead to design the third generation Bcr-Abl kinase inhibitors.
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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.