ArticleJournal of medicinal chemistry2015
Development of Alkyne-Containing Pyrazolopyrimidines To Overcome Drug Resistance of Bcr-Abl Kinase.
Article in Journal of medicinal chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 31 citations in OpenAlex.
- Multiple Molecule λ-Dynamics: Probing Drug Resistance with Concurrent Protein and Ligand Perturbations.The journal of physical chemistry letters · 2025Article
- Raman Spectroscopy as a Research and Diagnostic Tool in Clinical Hematology and Hematooncology.International journal of molecular sciences · 2024Review
- Selective Para-C-H Alkynylation of Aniline Derivatives by Pd/S,O-Ligand Catalysis.Chemistry (Weinheim an der Bergstrasse, Germany) · 2022Article
- High-Affinity Alkynyl Bisubstrate Inhibitors of NicotinamideJournal of medicinal chemistry · 2019Article
- Rigidification Dramatically Improves Inhibitor Selectivity for RAF Kinases.ACS medicinal chemistry letters · 2019Article
- Molecular biology as a tool for the treatment of cancer.Clinical and experimental medicine · 2018Review
- Effects of rigidity on the selectivity of protein kinase inhibitors.European journal of medicinal chemistry · 2018Article
- Development of a 4-aminopyrazolo[3,4-d]pyrimidine-based dual IGF1R/Src inhibitor as a novel anticancer agent with minimal toxicity.Molecular cancer · 2018Article
- Synthesis and identification of GZD856 as an orally bioavailable Bcr-AblJournal of enzyme inhibition and medicinal chemistry · 2017Article
- Induction of K562 Cell Apoptosis by As4S4 via Down-Regulating miR181.Medical science monitor : international medical journal of experimental and clinical research · 2017Article
- The Philadelphia chromosome in leukemogenesis.Chinese journal of cancer · 2016Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Despite the success of imatinib at inhibiting Bcr-Abl and treating chronic myelogenous leukemia (CML), resistance to the therapy occurs over time in patients. In particular, the resistance to imatinib caused by the gatekeeper mutation T315I in Bcr-Abl remains a challenge in the clinic. Inspired by the successful development of ponatinib to curb drug resistance, we hypothesize that the incorporation of an alkyne linker in other heterocyclic scaffolds can also achieve potent inhibition of Bcr-Abl(T315I) by allowing for simultaneous occupancy of both the active site and the allosteric pocket in the Abl kinase domain. Herein, we describe the design, synthesis, and characterization of a series of alkyne-containing pyrazolopyrimidines as Bcr-Abl inhibitors. Our results demonstrate that some alkyne-containing pyrazolopyrimidines potently inhibit not only Abl(T315I) in vitro but also Bcr-Abl(T315I) in cells. These pyrazolopyrimidines can serve as lead compounds for future development of novel targeted therapy to overcome drug resistance of CML.
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