A recent update on small‐molecule kinase inhibitors for targeted cancer therapy and their therapeutic insights from mass spectrometry‐based proteomic analysis

Lee, Pey Yee; Yeoh, Yeelon; Low, Teck Yew

doi:10.1111/febs.16442

Cited by 31 publications

(28 citation statements)

References 107 publications

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“…From 2011 to 2013, total of 14 kinase inhibitor drugs were approved by the FDA for various types of cancers. Since 1999, around 70 drugs got approval from FDA till Dec 2021 and still many more drugs are under clinical trial for many new kinase in hibitors [25,91,92].…”

Section: Fda Approved Drugs As Targetsmentioning

confidence: 99%

Protein kinases: Role of their dysregulation in carcinogenesis, identification and inhibition

et al. 2023

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Protein kinases belong to the phosphor-transferases superfamily of enzymes, which “activate” enzymes via phosphorylation. The kinome of an organism is the total set of genes in the genome, which encode for all the protein kinases. Certain mutations in the kinome have been linked to dysregulation of protein kinases, which in turn can lead to several diseases and disorders including cancer. In this review, we have briefly discussed the role of protein kinases in various biochemical processes by categorizing cancer associated phenotypes and giving their protein kinase examples. Various techniques have also been discussed, which are being used to analyze the structure of protein kinases, and associate their roles in the oncogenesis. We have also discussed protein kinase inhibitors and United States Federal Drug Administration (USFDA) approved drugs, which target protein kinases and can serve as a counter to protein kinase dysregulation and mitigate the effects of oncogenesis. Overall, this review briefs about the importance of protein kinases, their roles in oncogenesis on dysregulation and how their inhibition via various drugs can be used to mitigate their effects.

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Section: Fda Approved Drugs As Targetsmentioning

confidence: 99%

Protein kinases: Role of their dysregulation in carcinogenesis, identification and inhibition

et al. 2023

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“…MEK1/2 inhibitors, which bind at a particular cavity close to the ATP-binding site, are some of the well-studied type III inhibitors. Trametinib, Selumetinib, Binimetinib, and Cobimetinib are allosteric inhibitors of MEK and are among the MEK inhibitors currently approved by the FDA [38,[53][54][55][56]. The regions outside the ATP-binding sites are the focus of Type IV inhibitors, also known as substrate-directed inhibitors, which are allosteric inhibitors that do not overlap with Type III inhibitors.…”

Section: Targets For Developing Kinase Inhibitorsmentioning

confidence: 99%

“…These are less potent than other types of inhibitors and do not directly prevent binding at the kinase domain/ligand-polypeptide binding site. SSR128129E and WRG-28 are two examples of this type of kinase inhibitor, which inhibits the FGFR (extracellular domain of fibroblast growth factor receptor) family and DDRs (discoidin domain receptors), respectively [7,41,53,56,57]. The structured kinase mapping analyses revealed that approximately 200 kinases have wide-open cysteine available at the active sites, which could use in covalent inhibition [57].…”

Section: Targets For Developing Kinase Inhibitorsmentioning

confidence: 99%

Utilization of kinase inhibitors as novel therapeutic drug targets: A review

NISHAL¹,

JHAWAT²,

GUPTA³

et al. 2022

Oncology Research

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Kinase inhibitors are a significant and continuously developing division of target therapeutics. The drug discovery and improvement efforts have examined numerous attempts to target the signaling pathway of kinases. The Kinase inhibitors have been heralded as a game-changer in cancer treatment. For developing kinase inhibitors as a treatment for various non-malignant disorders like auto-immune diseases, is currently undergoing extensive research.It may be beneficial to investigate whether cell-specific kinase inhibitor administration enhances therapeutic efficacy and decreases adverse effects. The goal of the current review is to gain insight into the role of kinase inhibitors in facilitating effective target drug delivery for the treatment of various anti-inflammatory, auto-immune, and anticancer disorders. The aim of this review is also to shed light on drug discovery approaches for kinase inhibitors, their mode of action, and delivery approaches. The variation in the binding of kinases bestows different target approaches in drug design, which can be employed for designing the targeted molecules. Several target sites have been studied, exceeding the design of drugs for various diseases like cancer, Alzheimer's, rheumatoid arthritis, etc. Diverse delivery approaches have also been studied for the targeted application of kinase inhibitors.

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“…Fusion genes are used as the targets of the therapeutics of cancer patients. Speci cally, kinase inhibitors are the most frequently treated drugs for driver fusion gene-positive patients (1,2). There are diverse working mechanisms of human fusion proteins that are awaiting to be targeted by the drugs (3).…”

Section: Introductionmentioning

confidence: 99%

FusionPDB: a knowledgebase of human Fusion Proteins

Kumar

Tang

Yang

et al. 2023

Preprint

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Tumorigenic functions due to the formation of fusion genes were targeted for cancer therapeutics (i.e., kinase inhibitors). However, many fusion proteins are still awaiting being targeted for therapeutics in diverse cellular working mechanisms. Due to the lack of whole fusion protein sequences and whole 3D structures of the fusion proteins, it was hard to develop novel therapeutic approaches. To fill these critical gaps, we developed a new computational pipeline and a resource of human fusion proteins named FusionPDB, available at https://compbio.uth.edu/FusionPDB. FusionPDB provides ~ 43K fusion protein sequences (of 14.7K in-frame fusion genes, Level 1), 2300 + 1267 fusion protein 3D structures (of 2300 recurrent + 266 manually curated in-frame fusion genes, Level 2), and virtual screening results of 1267 fusion proteins (of 266 manually curated in-frame fusion genes, Level 3). FusionPDB is the only resource providing whole 3D structures of fusion proteins and comprehensive knowledge of human fusion proteins. It will be regularly updated until covering all human fusion proteins in the future.

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A recent update on small‐molecule kinase inhibitors for targeted cancer therapy and their therapeutic insights from mass spectrometry‐based proteomic analysis

Cited by 31 publications

References 107 publications

Protein kinases: Role of their dysregulation in carcinogenesis, identification and inhibition

Protein kinases: Role of their dysregulation in carcinogenesis, identification and inhibition

Utilization of kinase inhibitors as novel therapeutic drug targets: A review

FusionPDB: a knowledgebase of human Fusion Proteins

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