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INDEX

Introduction

Page

Tyrosine Kinase Receptors (RTKs) 1

The Epidermal Growth Factor Receptor EGFR 3

Growth Factor and Receptor Activation 6

EGFR Signalling Pathways 9

EGFR and Cancer 12

Gating EGFR 13

The Epidermal Growth Factor EGF Design of Tyrosine Kinase Inhibitors 14 17 EGFR inhibitors 20

News on the Clinical Use of EGFR inhibitors 26

Resistance to “EGFR-targeting” therapies 27

New Treatment Guidelines 28

Indirect and Direct Targeting of Angiogenesis Pathways 29

Vascular Endothelial Growth Factor and Receptors VEGF/VEGFR 29

VEGFR signalling 31

Anti-VEGFR Agents

Monoclonal Antibody

Small molecules TK Inhibitors

34 35 36

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Introduction to Experimental Section

VEGFR-2 small molecules Inhibitors

Anthranilamides

Pyrimidine Derivatives

40 41 43 New Pyridothiopyrano Pyrimidines 49

Experimental Section

62

Riferimenti

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