Recent advances in Bcr‐Abl tyrosine kinase inhibitors for overriding T315I mutation

Liu, Juan; Yuan, Zhen; Huang, Haoliang; Lei, Xiaoyong; Tang, Guotao; Cao, Xuan; Peng, Junmei

doi:10.1111/cbdd.13801

Cited by 30 publications

(22 citation statements)

References 78 publications

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“…Novel drugs targeting the mutant form of the protein, such as dasatinib and nilotinib are the only inhibitors that can block the activity of the T315I BCR-ABL mutation. These drugs have been developed to treat relapsed CML patients who have developed resistance to imatinib [40,41]. The acquisition of secondary mutations that prevent drug binding to the target kinase catalytic site, which has been shown for a range of oncogeneaddicted cancers, including EGFR in NSCLC, has been highlighted as a recurrent theme in the landscape of targeted therapy [42].…”

Section: Salient Features Of Oncogene Addictionmentioning

confidence: 99%

Targeting Oncogene Addiction for Cancer Therapy

Thapa¹,

Rather²,

Singh³

et al. 2022

Molecular Mechanisms in Cancer

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Oncogene addiction, a term first coined by Bernard Weinstein in 2000, refers to a condition where a tumor cell, despite harboring a multitude of genetic alterations, depends on a single oncogenic pathway or oncoprotein for sustained proliferation and survival. Several lines of evidence from mammalian cell culture models, genetically modified mice models, and human intervention trials of targeted drugs have revealed that many tumors, if not all, rely on oncogene addiction for sustained proliferation and survival. Oncogene addiction strongly impacts the therapeutic response of tumors to acute oncoprotein inhibition. An important implication of oncogene addiction is that inhibiting this critical pathway, on which cancer cells become dependent, can cause selective and specific cell death in cancer cells while sparing normal surrounding cells that are not oncogene addicted. However, the mechanism by which cancer cells become dependent on a single pathway or activated oncoprotein is not precisely understood in most cases. Thus, a better understanding of oncogene addiction may provide a rationale for improving current cancer therapies and help develop novel therapeutic strategies for the management of cancer.

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Section: Salient Features Of Oncogene Addictionmentioning

confidence: 99%

Targeting Oncogene Addiction for Cancer Therapy

Thapa¹,

Rather²,

Singh³

et al. 2022

Molecular Mechanisms in Cancer

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“…Some molecules prepared are in the preclinical stage, where many others are employed in the clinical research. Ponatinib is an IMPcontaining drug used in these researches (see Figure 2, compound 2) (2). Another review article states that Ponatinib is approved as an auxilary treatment molecule for chronic myelogenous leukemia (CML) and Philadelphia chromosomepositive acute lymphoblastic leukemia (ALL).…”

Section: Inhibitory Properties Of Imp On Many Enzymes Inhibition Of Bcr-abl Kinase Of Substituted Imidazopyridazine Scaffold As a Trustedmentioning

confidence: 99%

“…For the site-selective sp 2 C−H silylation of azines, Gu et al have devised a base-mediated synthetic method. Authors report that the conditions are mild, the protocol is simple, and for a diverse set of azines, the site selectivity is excellent.…”

Section: Site-selective C-h Silylation Of Azinesmentioning

confidence: 99%

“…IMP (compound 1, see Figure 1 below) has a structure and numbering scheme depicted in Figure 1. IMP is reported to be an inhibitor including, but not limited to, for the following enzymes: Break point cluster-Abelson (BCL-ABL) kinase (2), vascular endothelial growth factor (VEGF) Receptor 2 kinase (3), tumor necrosis factor alpha (4), Bruton's tyrosine kinase (BTK) (5), ATP-competitive mTOR (mammalian target of rapamycin) (6), PDE 10A (7), activin receptor-like kinase 2 (8), Pim kinase (9), deathassociated protein kinase (DAPK) (10), glycogen synthase kinase-3 (11), fibroblast growth factor receptor 1 (FGFR1) (12), dengue fever (13), tyrosine kinase 2 (2), and calcium-dependent protein kinase 1 (14). It has also been reported as an ingredient of anticancer drugs (15), antiparasitic (16), and antiproliferative agents (17), and used as radioligands for tropomyosin receptor kinase family (18).…”

Section: Introductionmentioning

confidence: 99%

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On the Biological Importance, Preparation, and Uses of Imidazo[1,2-b]pyridazine-Based Compounds

Akkurt

2021

Journal of the Turkish Chemical Society Section A: Chemistry

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While studying several pyridazine compounds, the author discovered imidazo[1,2-b]pyridazine (IMP), which is a very versatile compound class. It has been an inhibitor for many enzymes and also it is used as a brominating reagent in organic syntheses. Owing to its high biological activity, researchers have always considered including this molecule in their final structures. This humble attempt just aims to introduce this very powerful molecule to the readers, primarily of chemical origin, and should not be considered as a full treatise of, especially, the medicinal chemistry of the molecule. This work discusses the inhibitory effects, organic chemistry, applications in material chemistry, and theoretical studies of IMP and related molecules. The readers are hereby encouraged to work with medicinal chemists with the newly prepared molecules including this and similar molecules, in the struggle with many diseases like cancer, Alzheimer’s, and others.

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“…Zeta chain of T-cell receptor-associated protein kinase 70 (ZAP-70), B lymphocyte kinase (BLK), JAK2, tyrosine-protein kinase (LYN) and neurotrophic Receptor Tyrosine Kinase 3 (NTRK3) are found to be the most commonly mutated kinases in CLL [ 24 ]. The abelson tyrosine-protein kinase 1 (ABL1) mutants and their therapeutic inhibitors have been extensively reported to play a critical role in leukaemia and discussed in detail in recent reviews [ 25 , 26 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

Protein Tyrosine Kinases: Their Roles and Their Targeting in Leukemia

Bhanumathy

Amrutha

Vizeacoumar

et al. 2021

Cancers

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Protein kinases constitute a large group of enzymes catalysing protein phosphorylation and controlling multiple signalling events. The human protein kinase superfamily consists of 518 members and represents a complicated system with intricate internal and external interactions. Protein kinases are classified into two main families based on the ability to phosphorylate either tyrosine or serine and threonine residues. Among the 90 tyrosine kinase genes, 58 are receptor types classified into 20 groups and 32 are of the nonreceptor types distributed into 10 groups. Tyrosine kinases execute their biological functions by controlling a variety of cellular responses, such as cell division, metabolism, migration, cell–cell and cell matrix adhesion, cell survival and apoptosis. Over the last 30 years, a major focus of research has been directed towards cancer-associated tyrosine kinases owing to their critical contributions to the development and aggressiveness of human malignancies through the pathological effects on cell behaviour. Leukaemia represents a heterogeneous group of haematological malignancies, characterised by an uncontrolled proliferation of undifferentiated hematopoietic cells or leukaemia blasts, mostly derived from bone marrow. They are usually classified as chronic or acute, depending on the rates of their progression, as well as myeloid or lymphoblastic, according to the type of blood cells involved. Overall, these malignancies are relatively common amongst both children and adults. In malignant haematopoiesis, multiple tyrosine kinases of both receptor and nonreceptor types, including AXL receptor tyrosine kinase (AXL), Discoidin domain receptor 1 (DDR1), Vascular endothelial growth factor receptor (VEGFR), Fibroblast growth factor receptor (FGFR), Mesenchymal–epithelial transition factor (MET), proto-oncogene c-Src (SRC), Spleen tyrosine kinase (SYK) and pro-oncogenic Abelson tyrosine-protein kinase 1 (ABL1) mutants, are implicated in the pathogenesis and drug resistance of practically all types of leukaemia. The role of ABL1 kinase mutants and their therapeutic inhibitors have been extensively analysed in scientific literature, and therefore, in this review, we provide insights into the impact and mechanism of action of other tyrosine kinases involved in the development and progression of human leukaemia and discuss the currently available and emerging treatment options based on targeting these molecules.

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Recent advances in Bcr‐Abl tyrosine kinase inhibitors for overriding T315I mutation

Cited by 30 publications

References 78 publications

Targeting Oncogene Addiction for Cancer Therapy

Targeting Oncogene Addiction for Cancer Therapy

On the Biological Importance, Preparation, and Uses of Imidazo[1,2-b]pyridazine-Based Compounds

Protein Tyrosine Kinases: Their Roles and Their Targeting in Leukemia

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