ArticleACS omega2020
Nicotinamide-Ponatinib Analogues as Potent Anti-CML and Anti-AML Compounds.
Article in ACS omega, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 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
8 citing papers in PubMed, 18 citations in OpenAlex.
- Identification of alkynyl nicotinamide HSN748 as a RET solvent-front mutant inhibitor with intracranial efficacy.RSC medicinal chemistry · 2025Article
- Exploring the Potential of Pyridine Carboxylic Acid Isomers to Discover New Enzyme Inhibitors.Drug design, development and therapy · 2025Review
- Alkynyl nicotinamides show antileukemic activity in drug-resistant acute myeloid leukemia.The Journal of clinical investigation · 2024Article
- Pyrazine-based small molecule kinase inhibitors: clinical applications and patent review (2019-2023).Future medicinal chemistry · 2024Review
- The Progress of Small Molecule Targeting BCR-ABL in the Treatment of Chronic Myeloid Leukemia.Mini reviews in medicinal chemistry · 2024Review
- Designing Novel BCR-ABL Inhibitors for Chronic Myeloid Leukemia with Improved Cardiac Safety.Journal of medicinal chemistry · 2022Article
- Discovery and Optimization of Seven-Membered Lactam-Based Compounds to Phenocopy the Inhibition of the Aurora Kinase B.ACS medicinal chemistry letters · 2022Article
- N-Heterocyclic carbene (NHC)-catalyzed oxidation of unactivated aldimines to amidesRSC advances · 2022Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ponatinib is a multikinase inhibitor that is used to treat chronic myeloid leukemia patients harboring mutated ABL1(T315I) kinase. Due to the potent inhibition of FLT3, RET, and fibroblast growth factor receptors (FGFRs), it is also being evaluated against acute myeloid leukemia (AML), biliary, and lung cancers. The multikinase inhibition profile of ponatinib may also account for its toxicity, thus analogs with improved kinase selectivity or different kinase inhibition profiles could be better tolerated. The introduction of nitrogen into drug compounds can enhance efficacy and drug properties (a concept called "necessary nitrogen"). Here, we introduce additional nitrogen into the benzamide moiety of ponatinib to arrive at nicotinamide analogs. A nicotinamide analogue of ponatinib, HSN748, retains activity against FLT3, ABL1, RET, and PDGFRα/β but loses activity against c-Src and P38α. MNK1 and 2 are key kinases that phosphorylate eIF4E to regulate the protein translation complex. MNK also modulates mTORC1 signaling and contributes to rapamycin resistance. Inhibitors of MNK1 and 2 are being evaluated for anticancer therapy. Ponatinib is not a potent inhibitor of MNK1 or 2, but the nicotinamide analogs are potent inhibitors of MNKs. This illustrates a powerful demonstration of the necessary nitrogen concept to alter both the potency and selectivity of drugs.
Identifiers
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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.