Recent Advancements in Small Molecule Inhibitors of Insulin–like Growth Factor-1 Receptor (IGF-1R) Tyrosine Kinase as Anticancer agents

Vascular endothelial growth factor receptor 2 (VEGFR-2) binds to VEGFR-A, VEGFR-C and VEGFR-D and participates in the formation of tumor blood vessels, mediates the proliferation of endothelial cells, enhances microvascular permeability, and blocks apoptosis. Blocking or downregulating the signal transduction of VEGFR is the main way to discover new drugs for many human angiogenesis-dependent malignancies. Mesenchymal epithelial transfer factor tyrosine kinase (c-Met) is a high affinity receptor for hepatocyte growth factor (HGF). Abnormal c-Met signaling plays an important role in the formation, invasion and metastasis of human tumors. Therefore, the HGF/c-Met signaling pathway has become a significant target for cancer treatment. Related studies have shown that the conduction of the VEGFR and c-Met signaling pathways has a synergistic effect in inducing angiogenesis and inhibiting tumor growth. In recent years, multi-target small molecule inhibitors have become a research hotspot, among which the research of VEGFR and c-Met dual-target small molecule inhibitors has become more and more extensive. In this review, we comprehensively summarize the chemical structures and biological characteristics of novel VEGFR/c-Met dual-target small-molecule inhibitors in the past five years.

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Feedback Mechanisms Promote Cooperativity for Small Molecule Inhibitors of Epidermal and Insulin-Like Growth Factor Receptors

Cancer Research ◽

10.1158/0008-5472.can-07-6720 ◽

2008 ◽

Vol 68 (20) ◽

pp. 8322-8332 ◽

Cited By ~ 148

Author(s):

Elizabeth Buck ◽

Alexandra Eyzaguirre ◽

Maryland Rosenfeld-Franklin ◽

Stuart Thomson ◽

Mark Mulvihill ◽

...

Keyword(s):

Growth Factor ◽

Small Molecule ◽

Small Molecule Inhibitors ◽

Growth Factor Receptors ◽

Insulin Like Growth Factor ◽

Feedback Mechanisms

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Chapter 14 Recent Progress in the Development of Small Molecule Inhibitors of Insulin-Like Growth Factor-1 Receptor Kinase

Annual Reports in Medicinal Chemistry - Annual Reports in Medicinal Chemistry Volume 44 ◽

10.1016/s0065-7743(09)04414-5 ◽

2009 ◽

pp. 281-299 ◽

Cited By ~ 7

Author(s):

Mark D. Wittman ◽

Upender Velaparthi ◽

Dolatrai M. Vyas

Keyword(s):

Growth Factor ◽

Small Molecule ◽

Recent Progress ◽

Small Molecule Inhibitors ◽

Insulin Like Growth Factor ◽

Receptor Kinase

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Targeting Small Molecule Tyrosine Kinases by Polyphenols: New Move Towards Anti-tumor Drug Discovery

Current Drug Discovery Technologies ◽

10.2174/1570163816666190808120843 ◽

2020 ◽

Vol 17 (5) ◽

pp. 585-615 ◽

Cited By ~ 1

Author(s):

Nikhil S. Sakle ◽

Shweta A. More ◽

Sachin A. Dhawale ◽

Santosh N. Mokale

Keyword(s):

Growth Factor ◽

Tyrosine Kinase ◽

Cancer Cells ◽

Small Molecule ◽

Anaplastic Lymphoma Kinase ◽

Tyrosine Kinases ◽

Growth Factor Receptor ◽

Myelogenous Leukemia ◽

Cell Functions ◽

Anaplastic Lymphoma

Background: Cancer is a complex disease involving genetic and epigenetic alteration that allows cells to escape normal homeostasis. Kinases play a crucial role in signaling pathways that regulate cell functions. Deregulation of kinases leads to a variety of pathological changes, activating cancer cell proliferation and metastases. The molecular mechanism of cancer is complex and the dysregulation of tyrosine kinases like Anaplastic Lymphoma Kinase (ALK), Bcr-Abl (Fusion gene found in patient with Chronic Myelogenous Leukemia (CML), JAK (Janus Activated Kinase), Src Family Kinases (SFKs), ALK (Anaplastic lymphoma Kinase), c-MET (Mesenchymal- Epithelial Transition), EGFR (Epidermal Growth Factor receptor), PDGFR (Platelet-Derived Growth Factor Receptor), RET (Rearranged during Transfection) and VEGFR (Vascular Endothelial Growth Factor Receptor) plays major role in the process of carcinogenesis. Recently, kinase inhibitors have overcome many problems of traditional cancer chemotherapy as they effectively separate out normal, non-cancer cells as well as rapidly multiplying cancer cells. Methods: Electronic databases were searched to explore the small molecule tyrosine kinases by polyphenols with the help of docking study (Glide-7.6 program interfaced with Maestro-v11.3 of Schrödinger 2017) to show the binding energies of polyphenols inhibitor with different tyrosine kinases in order to differentiate between the targets. Results: From the literature survey, it was observed that the number of polyphenols derived from natural sources alters the expression and signaling cascade of tyrosine kinase in various tumor models. Therefore, the development of polyphenols as a tyrosine kinase inhibitor against targeted proteins is regarded as an upcoming trend for chemoprevention. Conclusion: In this review, we have discussed the role of polyphenols as chemoreceptive which will help in future for the development and discovery of novel semisynthetic anticancer agents coupled with polyphenols.

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