Novel <i>BCR-ABL1</i> tyrosine kinase inhibitors in the treatment of chronic myeloid leukemia

Malik, Sara; Hassan, Shahzeb; Eşkazan, Ahmet Emre

doi:10.1080/17474086.2021.1990034

Cited by 16 publications

(3 citation statements)

References 19 publications

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“…Platelets in cancer patients exhibit a pivotal role in disease progression, metastasis, and, more importantly, in CAT [ 80 , 81 ]. There is an urgent need for new therapies that can target not only the cancer cells but also the platelets, which are so eager to help them survive longer and migrate faster [ 13 , 31 , 82 ]. By minimizing thrombotic complications, cancer patients could have a better quality of life [ 53 , 83 ].…”

Section: Discussionmentioning

confidence: 99%

“…Treatment with tyrosine kinase inhibitors (TKIs), as targeted therapeutic drugs in oncology, has already revealed great results [ 16 ]. The first TKI used was imatinib, but due to many resistances in CML treatment [ 16 , 17 ], it was urgent to develop second-generation (dasatinib, nilotinib, and bosutinib) [ 18 , 19 , 20 , 21 , 22 , 23 , 24 ], third-generation (ponatinib, olverembatinib, and vodobatinib) [ 18 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ], and fourth-generation (PF-114) TKIs [ 31 ]. The deadliest mutation, and in fact a frequent one, that develops resistance to nilotinib is the “gatekeeper” mutation T315I, where isoleucine replaces threonine in position 315 of Bcr-Abl [ 10 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

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Synthesis of Novel Nilotinib Analogues and Biological Evaluation of Their Antiplatelet Activity and Functionality towards Cancer Cell Proliferation In Vitro

Pechlivani,

Ntemou,

Pantazi

et al. 2024

Pharmaceuticals

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Nilotinib, a second-generation tyrosine kinase inhibitor for the treatment of chronic myelogenous leukemia (CML), inhibits Bcr-Abl tyrosine kinase activity and proliferation of Bcr-Abl-expressing cells, as well as other malignancies. In the present study, new nilotinib analogues were synthesized and fully characterized. A platelet aggregation assay was performed, and the expression of P-selectin and PAC-1, as well as the effect on the proliferation of healthy endothelial cells, were evaluated. The expression and antimetastatic effects of E-cadherin and N-cadherin were assessed. The analogues inhibited platelet aggregation in a statistically significant manner compared to nilotinib, while they exhibited a strong inhibitory effect on P-selectin and PAC-1 expression when activated by AA. All three analogues caused arrest in the mitosis phase of the HepG2 cell cycle, while analogue-1 exhibited the most potent apoptotic effect compared to nilotinib. Interestingly, none of them promoted apoptosis in HUVECs. All the analogues reduced the expression of E- and N-cadherin in different amounts, while the analogues-1 and -3 exhibited similar antimigratory effects on HepG2 cells. The results of this study reveal considerable potential to develop new tyrosine kinase inhibitors with improved antiplatelet and antitumor properties.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synthesis of Novel Nilotinib Analogues and Biological Evaluation of Their Antiplatelet Activity and Functionality towards Cancer Cell Proliferation In Vitro

Pechlivani,

Ntemou,

Pantazi

et al. 2024

Pharmaceuticals

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“…We describe new specific drugs, focusing on the mechanisms of action, efficacy and safety. In detail, the molecules acting on BCR-ABL include Asciminib (ABL001), Olverembatinib (HQP1351), PF-114 and K0706 (58).…”

Section: New Bcr-abl and Non-bcr-abl Targeted Therapiesmentioning

confidence: 99%

Potential Approaches Versus Approved or Developing Chronic Myeloid Leukemia Therapy

et al. 2021

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Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of patients with chronic myeloid leukemia (CML). However, continued use of these inhibitors has contributed to the increase in clinical resistance and the persistence of resistant leukemic stem cells (LSCs). So, there is an urgent need to introduce additional targeted and selective therapies to eradicate quiescent LSCs, and to avoid the relapse and disease progression. Here, we focused on emerging BCR-ABL targeted and non-BCR-ABL targeted drugs employed in clinical trials and on alternative CML treatments, including antioxidants, oncolytic virus, engineered exosomes, and natural products obtained from marine organisms that could pave the way for new therapeutic approaches for CML patients.

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Asciminib: first FDA approved allosteric inhibitor of BCR-ABL1 for the treatment of chronic myeloid leukemia

2023

Med Chem Res

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Novel BCR-ABL1 tyrosine kinase inhibitors in the treatment of chronic myeloid leukemia

Cited by 16 publications

References 19 publications

Synthesis of Novel Nilotinib Analogues and Biological Evaluation of Their Antiplatelet Activity and Functionality towards Cancer Cell Proliferation In Vitro

Synthesis of Novel Nilotinib Analogues and Biological Evaluation of Their Antiplatelet Activity and Functionality towards Cancer Cell Proliferation In Vitro

Potential Approaches Versus Approved or Developing Chronic Myeloid Leukemia Therapy

Asciminib: first FDA approved allosteric inhibitor of BCR-ABL1 for the treatment of chronic myeloid leukemia

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