Drugs That Inhibit Signaling Pathways for Tumor Cell Growth and Proliferation

Avendaño, Carmen; Menéndez, J. Carlos

doi:10.1016/b978-0-444-62649-3.00010-7

Cited by 9 publications

(8 citation statements)

References 280 publications

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“…Fusion of Bcr and Abl genes leads to constitutive activation of Bcr-Abl tyrosine kinase, causing CML cells to grow and divide excessively [13]. Protein kinases are enzymes that regulate the biological activity of proteins by phosphorylation of specific amino acids with adenosine triphosphate (ATP) to induce conformational changes from the inactive to the active form [14]. Protein Kinases have been implicated in cell proliferation and many have transforming capacity making them oncoproteins [14].…”

Section: Signal Transduction Inhibitorsmentioning

confidence: 99%

“…Protein kinases are enzymes that regulate the biological activity of proteins by phosphorylation of specific amino acids with adenosine triphosphate (ATP) to induce conformational changes from the inactive to the active form [14]. Protein Kinases have been implicated in cell proliferation and many have transforming capacity making them oncoproteins [14]. Consequently, protein kinases have been extensively studied as a signal transduction inhibitor pathway in targeted drug therapy [13][14][15].…”

Section: Signal Transduction Inhibitorsmentioning

confidence: 99%

“…Protein Kinases have been implicated in cell proliferation and many have transforming capacity making them oncoproteins [14]. Consequently, protein kinases have been extensively studied as a signal transduction inhibitor pathway in targeted drug therapy [13][14][15].…”

Section: Signal Transduction Inhibitorsmentioning

confidence: 99%

“…One of the most successful molecular targets of anticancer agents is the protein tyrosine kinase inhibitor imatinib (Gleevec®), for the treatment of Ph positive CML [4,9,10,[12][13][14][15]. Its success is based on the extreme "addiction" of CML cells to Bcr-Abl fusion pathway.…”

Section: Signal Transduction Inhibitorsmentioning

confidence: 99%

“…Its success is based on the extreme "addiction" of CML cells to Bcr-Abl fusion pathway. Imatinib is designed as an ATP mimic which acts by blocking tyrosine phosphorylation, it competitively binds to the ATP binding site on Bcr-Abl fusion protein to disrupt tyrosine kinase activity [14]. It is reported to have up to 80% response rate in Ph positive CML patients [14].…”

Section: Signal Transduction Inhibitorsmentioning

confidence: 99%

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The Principles behind Targeted Therapy for Cancer Treatment

Albusairi¹,

Khajah²

2020

Tumor Progression and Metastasis

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The advent of molecular and genetic advancement in the field of oncology research has led to a shift in the treatment of various forms of cancer from traditional chemotherapeutics to targeted therapy. The principle behind targeted therapy is utilizing therapeutics designed to interfere with specific molecules that have a relatively specific or higher expression profile in cancer cells and are critical for cancer growth and progression. These were designed as mechanistic therapeutics in the form of small molecules and monoclonal antibodies. Currently, they have been modified to incorporate passive or active targeting delivery systems to improve their specific distribution and enhance cytotoxicity towards cancer cells while simultaneously reducing their systemic toxicity profile. Passive targeting employs encapsulated delivery systems to take advantage of the enhanced permeation and retention effect of the tumor microenvironment, while active targeting relies on receptor mediated interactions, such as cell surface ligands conjugated to the therapeutic moiety. A synergistic strategy for cancer therapy is evolving, where precision medicine acts as a diagnostic prerequisite for targeted therapy via prognostic biomarkers and tumor genotyping. Despite the plethora of research undertaken in targeted therapy, limited numbers were approved for clinical use, and significant challenges remain to be addressed.

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Section: Signal Transduction Inhibitorsmentioning

confidence: 99%

Section: Signal Transduction Inhibitorsmentioning

confidence: 99%

Section: Signal Transduction Inhibitorsmentioning

confidence: 99%

Section: Signal Transduction Inhibitorsmentioning

confidence: 99%

Section: Signal Transduction Inhibitorsmentioning

confidence: 99%

See 3 more Smart Citations

The Principles behind Targeted Therapy for Cancer Treatment

Albusairi¹,

Khajah²

2020

Tumor Progression and Metastasis

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Pyridines, Dihydropyridines and Piperidines: An Outline on Synthesis and Biological Activities

Rajbongshi¹,

Dam²,

Patel³

2022

N-Heterocycles

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Selected arylsulphonyl pyrazole derivatives as potential Chk1 kinase ligands—computational investigations

et al. 2020

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Protein kinases control diversity of biochemical processes in human organism. Checkpoint 1 kinase (Chk1) is an important element of the checkpoint signalling pathways and is responsible for DNA damage repair. Hence, this kinase plays an essential role in cancer cells survival and has become an important target for anticancer agents. Our previous investigations showed that some arylsulphonyl indazole derivatives displayed anticancer effect in vitro. In the present study, in order to verify possibility of interactions of pyrazole and indazole derivatives with Chk1, we focused on the docking of selected tosyl derivatives of indazole and condensed pyrazole 1–7 to the Chk1 pocket, analysis of interactions involving optimized ligand–protein system using DFT formalism, and estimation of the interaction enthalpy of the ligand–protein complex by applying the PM7 method. The estimation of binding affinity seems to indicate that the indazole 5-substituted with 3,5-dimethylpyrazole 4 and condensed pyrazoloquinoline derivative 7 fit the best to the Chk1-binding pocket. The values of the energy of interaction, i.e. the enthalpy change (ΔHint), were between − 85.06 and − 124.04 kcal mol−1 for the optimized ligand–Chk1 complexes. The relaxation of the ligands within the complexes azole–protein as well as the distribution of hydrogen contacts between the ligands and kinase pocket amino acids was also analysed using molecular dynamics as a supporting method.

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Drugs That Inhibit Signaling Pathways for Tumor Cell Growth and Proliferation

Cited by 9 publications

References 280 publications

The Principles behind Targeted Therapy for Cancer Treatment

The Principles behind Targeted Therapy for Cancer Treatment

Pyridines, Dihydropyridines and Piperidines: An Outline on Synthesis and Biological Activities

Selected arylsulphonyl pyrazole derivatives as potential Chk1 kinase ligands—computational investigations

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