Abstract
All cancers arise as a result of the acquisition of a series of fixed DNA
sequence abnormalities, mutations, many of which ultimately confer a growth
advantage upon the cells in which they have occurred. Protein kinases have
been implicated in many aspects of tumorigenesis and protein kinase inhibitors
(PKIs) have there of arisen as a major therapeutic class of compounds for the
treatment of cancer. The plethora of new potential therapeutic drugs have made
selection and validation of novel molecular targets of paramount importance
First in place, BioSeeker has surveyed protein kinase inhibitors in oncology
and identified 110 drug targets, belonging to 210 protein kinase inhibitor
drugs. This report, The Drug Target Atlas of Protein Kinase Inhibitors in
Oncology, is an open landscape of resources to build, fuel, and drive your
scientific competitive vehicle for the advancement of new protein kinase
inhibitor drugs in oncology
In the report, BioSeeker reports on 139 unique drug target combinations, each
comprised of a different collection or mix of individually defined targets,
for 210 PKI drugs designed for the treatment of more than 50 different cancer
indications. The highest degree of distinctiveness among PKIs is achieved by
sorting each of them according to targeted cancer indication, drug target mix,
and drug compound type. At the same time we are also identifying peer groups
of drugs, that is, drugs we consider suitable for head-to-head comparison
during drug development
To fuel the scientific and competitive thinking, BioSeeker opens the gate into
the presence and relevance of protein-protein interactions between identified
PKI drug targets. No less than 519 protein-protein interactions were
recognized among 98 of the 110 included PKI drug targets
The report by the numbers:
- 300+ pages, with almost a hundred different tables. Includes close to
1,000 active links to related resources on the Internet
- 210 Protein kinase inhibitor drugs, under development by 107
investigators, are included, covering more than 600 developmental projects in
cancer
- 110 Unique, in-depth, drug target profiles, highlighting twelve themes
about the drug target, i.e. protein-protein interaction with other PKI drug
targets, linked cancer indications, presence in the Cancer Genome Project etc
- 139 Unique drug target combinations of PKI drugs
- 519 protein-protein interactions among PKI drug targets
- 20 Major signaling pathways covered
Table of Contents
1 Executive Summary
2 About Cancer Highlights
3 Methodologies
4 Table of Contents
- 4.1 List of Figures
- 4.2 List of Tables
5 Introduction
6 PKI Drug Compound Types and Sub-cellular Localizations of Targets
7 The Cancer Genome Project and Protein Kinase Inhibitors
- 7.1 PKI Drug Targets Present in the Cancer Gene Census and in the
Catalogue of Somatic Mutations in Cancer
8 Protein Expression Profiles of PKI Drug Targets in Human
- 8.1 Expression in Normal Tissues and Cancer Tissues
- 8.2 Expression in Human Cancer Cell Lines and Primary Cells
9 Protein Kinase Inhibitors in Major Cell Signaling Pathways
- 9.1 Alpha6 Beta4 Integrin Signaling Pathway
- 9.2 Androgen Receptor Signaling Pathway
- 9.3 B Cell Receptor Signaling Pathway
- 9.4 EGFR1 Signaling Pathway
- 9.5 Hedgehog Signaling Pathway
- 9.6 ID Signaling Pathway
- 9.7 IL-1 Signaling Pathway
- 9.8 IL-2 Signaling Pathway
- 9.9 IL-3 Signaling Pathway
- 9.10 IL-4 Signaling Pathway
- 9.11 IL-5 Signaling Pathway
- 9.12 IL-6 Signaling Pathway
- 9.13 IL-7 Signaling Pathway
- 9.14 IL-9 Signaling Pathway
- 9.15 Kit Receptor Signaling Pathway
- 9.16 Notch Signaling Pathway
- 9.17 T Cell Receptor Signaling Pathway
- 9.18 TGF-beta Receptor Signaling Pathway
- 9.19 TNF-alpha Signaling Pathway
- 9.20 Wnt Signaling Pathway
10 Protein-Protein Interactions Between Identified PKI Drug Targets
11 Available Biological Structure Data on PKI Drug Targets
12 Drug Target Profiles of Protein Kinase Inhibitory Drug Targets in Oncology
- 12.1 Kinase Activity Target
- 12.1.1 Kinase Activity
- 12.1.2 Protein Serine/Threonine Kinase Activity
- 12.1.3 Lipid Kinase Activity
- 12.1.4 Protein Threonine/Tyrosine Kinase Activity
- 12.1.5 Protein-Tyrosine Kinase Activity
- 12.1.6 Receptor Activity
- 12.1.7 Receptor Signaling Protein Serine/Threonine Kinase Activity
- 12.1.8 Transmembrane Receptor Protein Tyrosine Kinase Activity
- 12.2 Non Kinase Activity Targets
- 12.2.1 Carboxy-lyase Activity
- 12.2.2 Cell Adhesion Molecule Activity
- 12.2.3 Chaperone activity
- 12.2.4 Cysteine-type Peptidase Activity
- 12.2.5 DNA Topoisomerase Activity
- 12.2.6 DNA-Directed DNA Polymerase Activity
- 12.2.7 Growth Factor Activity
- 12.2.8 Hormone Activity
- 12.2.9 Hydrolase Activity
- 12.2.10 Kinase Regulator Activity
- 12.2.11 Ligase Activity
- 12.2.12 Lipid Phosphatase Activity
- 12.2.13 Oxidoreductase Activity
- 12.2.14 Protein Binding
- 12.2.15 Receptor Binding
- 12.2.16 Receptor Signaling Complex Scaffold Activity
- 12.2.17 RNA Binding
- 12.2.18 Structural Constituent of Cytoskeleton
- 12.2.19 Transcription Factor Activity
- 12.2.20 Transcription Regulator Activity
- 12.2.21 Translation Regulator Activity
- 12.2.22 Transporter Activity
13 Protein Kinase Inhibitor Drug Target Mix by Cancer Indications
- 13.1 Basal Cell Cancer
- 13.2 Biliary Cancer
- 13.3 Bladder Cancer
- 13.4 Bone Cancer
- 13.5 Brain Cancer
- 13.6 Breast Cancer
- 13.7 Carcinoid
- 13.8 Cervical Cancer
- 13.9 Cervical Dysplasia
- 13.10 Chemotherapy-induced Bone Marrow Anemia
- 13.11 CNS Cancer
- 13.12 Colorectal Cancer
- 13.13 Endometrial Cancer
- 13.14 Fallopian Tube Cancer
- 13.15 Gastrointestinal Cancer
- 13.15.1 Gastrointestinal Stomach Cancer
- 13.15.2 Gastrointestinal Stromal Cancer
- 13.16 Head and Neck Cancer
- 13.17 Leukemia
- 13.17.1 Acute Lymphocytic Leukemia
- 13.17.2 Acute Myelogenous Leukemia
- 13.17.3 Chronic Lymphocytic Leukemia
- 13.17.4 Chronic Myelogenous Leukemia
- 13.18 Liver Cancer
- 13.19 Lung Cancer
- 13.19.1 Non-Small Cell Lung Cancer
- 13.19.2 Small Cell Lung Cancer
- 13.20 Lymphoma
- 13.20.1 B-cell Lymphoma
- 13.20.2 Hodgkin' s Lymphoma
- 13.20.3 Non-Hodgkin`s Lymphoma
- 13.20.4 T-cell Lymphoma
- 13.21 Melanoma
- 13.22 Mesothelioma
- 13.23 Myelodysplastic syndrome
- 13.24 Myeloma
- 13.25 Nasopharyngeal Cancer
- 13.26 Oesophageal Cancer
- 13.27 Ovarian Cancer
- 13.28 Pancreatic Cancer
- 13.29 Peritoneal Cancer
- 13.30 Prostate Cancer
- 13.31 Renal Cancer
- 13.31.1 Renal Cell Carcinoma
- 13.32 Sarcoma
- 13.33 Squamous Cell Cancer
- 13.34 Testicular Cancer
- 13.35 Thymoma
- 13.36 Thyroid Cancer
14 Protein Kinase Inhibitor Drugs and Targets by Companies
- 14.1 Australia
- 14.2 Belgium
- 14.3 Canada
- 14.4 China
- 14.5 Cuba
- 14.6 Denmark
- 14.7 France
- 14.8 Germany
- 14.9 India
- 14.10 Italy
- 14.11 Japan
- 14.12 New Zealand
- 14.13 South Korea
- 14.14 Spain
- 14.15 Switzerland
- 14.16 United Kingdom
- 14.17 USA
15 Disclaimer
16 Drug Index
17 Company Index
18 Appendix I: PKI Drug Target Mix
List of Figures
- Figure 1: Distribution of Drug Compound Types Among Protein Kinase
Inhibitors
List of Tables
- Table 1: Compound Type Versus Primary and Alternate Localization of Drug
Target
- Table 2: Probability Ranking of Identified Drug Targeted Protein Kinases
to Actually Carry ' Driver' Mutations Contributing to the Development of Cancers
- Table 3: PKI Drug Targets Present in the Catalogue of Somatic Mutations in
Cancer and in the Cancer Gene Census
- Table 4: Available Protein Expression Profiles of PKI Drug Targets
- Table 5: Protein Kinase Inhibitors and Cell Signaling: An Overview
- Table 6: PKI Drug Targets in the Alpha6 Beta4 Integrin Signaling Pathway
- Table 7: PKI Drug Targets in the Androgen Receptor Signaling Pathway
- Table 8: PKI Drug Targets in the B Cell Receptor Signaling Pathway
- Table 9: PKI Drug Targets in the EGFR1 Signaling Pathway
- Table 10: PKI Drug Targets in the Hedgehog Signaling Pathway
- Table 11:PKI Drug Targets in the ID Signaling Pathway
- Table 12:PKI Drug Targets in the IL-1 Signaling Pathway
- Table 13:PKI Drug Targets in the IL-2 Signaling Pathway
- Table 14:PKI Drug Targets in the IL-3 Signaling Pathway
- Table 15:PKI Drug Targets in the IL-4 Signaling Pathway
- Table 16: PKI Drug Targets in the IL-5 Signaling Pathway
- Table 17: PKI Drug Targets in the IL-6 Signaling Pathway
- Table 18: PKI Drug Targets in the IL-7 Signaling Pathway
- Table 19: PKI Drug Targets in the IL-9 Signaling Pathway
- Table 20: PKI Drug Targets in the Kit Receptor Signaling Pathway
- Table 21: PKI Drug Targets in the Notch Signaling Pathway
- Table 22: PKI Drug Targets in the T Cell Receptor Signaling Pathway
- Table 23: PKI Drug Targets in the TGF-beta Receptor Signaling Pathway
- Table 24: PKI Drug Targets in the TNF-alpha Signaling Pathway
- Table 25: PKI Drug Targets in the Wnt Signaling Pathway
- Table 26: Protein-Protein Interactions Between Identified PKI Drug Targets
- Table 27: Number of Available Biological Structures on PKI Drug Targets
- Table 28: Overview of Drug Target Profile Themes
- Table 29: Number of Unique PKI Drug Target Mixes Reported by Cancer
Indication
- Table 30: PKI Drug Target Mix for the Treatment of Basal Cell Cancer
According to the Compound Type and Developmental Stage of Drug
- Table 31: PKI Drug Target Mix for the Treatment of Biliary Cancer
According to the Compound Type and Developmental Stage of Drug
- Table 32: PKI Drug Target Mix for the Treatment of Bladder Cancer
According to the Compound Type and Developmental Stage of Drug
- Table 33: PKI Drug Target Mix for the Treatment of Bone Cancer According
to the Compound Type and Developmental Stage of Drug
- Table 34: PKI Drug Target Mix for the Treatment of Brain Cancer According
to the Compound Type and Developmental Stage of Drug
- Table 35: PKI Drug Target Mix for the Treatment of Breast Cancer According
to the Compound Type and Developmental Stage of Drug
- Table 36: PKI Drug Target Mix for the Treatment of Carcinoid According to
the Compound Type and Developmental Stage of Drug
- Table 37: PKI Drug Target Mix for the Treatment of Cervical Cancer
According to the Compound Type and Developmental Stage of Drug
- Table 38: PKI Drug Target Mix for the Treatment of Cervical Dysplasia
According to the Compound Type and Developmental Stage of Drug
- Table 39: PKI Drug Target Mix for the Treatment of Chemotherapy-induced
Bone Marrow Anemia According to the Compound Type and Developmental Stage of
Drug
- Table 40: PKI Drug Target Mix for the Treatment of CNS Cancer According to
the Compound Type and Developmental Stage of Drug
- Table 41: PKI Drug Target Mix for the Treatment of Colorectal Cancer
According to the Compound Type and Developmental Stage of Drug
- Table 42: PKI Drug Target Mix for the Treatment of Endometrial Cancer
According to the Compound Type and Developmental Stage of Drug
- Table 43: PKI Drug Target Mix for the Treatment of Fallopian Tube Cancer
According to the Compound Type Developmental Stage of Drug
- Table 44: PKI Drug Target Mix for the Treatment of Gastrointestinal Cancer
According to the Compound Type and Developmental Stage of Drug
- Table 45: PKI Drug Target Mix for the Treatment of Gastrointestinal,
Stomach Cancer According to the Compound Type and Developmental Stage of Drug
- Table 46: PKI Drug Target Mix for the Treatment of Gastrointestinal,
Stromal Cancer According to the Compound Type and Developmental Stage of Drug
- Table 47: PKI Drug Target Mix for the Treatment of Head and Neck Cancer
According to the Compound Type and Developmental Stage of Drug
- Table 48: PKI Drug Target Mix for the Treatment of Leukemia According to
the Compound Type and Developmental Stage of Drug
- Table 49: PKI Drug Target Mix for the Treatment of Acute Lymphocytic
Leukemia According to the Compound Type and Developmental Stage of Drug
- Table 50: PKI Drug Target Mix for the Treatment of Acute Myelogenous
Leukemia According to the Compound Type and Developmental Stage of Drug
- Table 51: PKI Drug Target Mix for the Treatment of Chronic Lymphocytic
Leukemia According to the Compound Type and Developmental Stage of Drug
- Table 52: PKI Drug Target Mix for the Treatment of Chronic Myelogenous
Leukemia According to the Compound Type and Developmental Stage of Drug
- Table 53: PKI Drug Target Mix for the Treatment of Liver Cancer According
to the Compound Type and Developmental Stage of Drug
- Table 54: PKI Drug Target Mix for the Treatment of Lung Cancer According
to the Compound Type and Developmental Stage of Drug
- Table 55: PKI Drug Target Mix for the Treatment of Non-Small Cell Lung
Cancer According to the Compound Type and Developmental Stage of Drug
- Table 56: PKI Drug Target Mix for the Treatment of Small Cell Lung Cancer
According to the Compound Type and Developmental Stage of Drug
- Table 57: PKI Drug Target Mix for the Treatment of Lymphoma According to
the Compound Type and Developmental Stage of Drug
- Table 58: PKI Drug Target Mix for the Treatment of B-cell Lymphoma
According to the Compound Type and Developmental Stage of Drug
- Table 59: PKI Drug Target Mix for the Treatment of Hodgkin' s Lymphoma
According to the Compound Type and Developmental Stage of Drug
- Table 60: PKI Drug Target Mix for the Treatment of Non-Hodgkin' s Lymphoma
According to the Compound Type and Developmental Stage of Drug
- Table 61: PKI Drug Target Mix for the Treatment of T-cell Lymphoma
According to the Compound Type and Developmental Stage of Drug
- Table 62: PKI Drug Target Mix for the Treatment of Melanoma According to
the Compound Type and Developmental Stage of Drug
- Table 63: PKI Drug Target Mix for the Treatment of Mesothelioma According
to the Compound Type and Developmental Stage of Drug
- Table 64: PKI Drug Target Mix for the Treatment of Myelodysplastic
Syndrome According to the Compound Type and Developmental Stage of Drug
- Table 65: PKI Drug Target Mix for the Treatment of Myeloma According to
the Compound Type and Developmental Stage of Drug
- Table 66: PKI Drug Target Mix for the Treatment of Multiple Myeloma
According to the Compound Type and Developmental Stage of Drug
- Table 67: PKI Drug Target Mix for the Treatment of Nasopharyngeal Cancer
According to the Compound Type and Developmental Stage of Drug
- Table 68: PKI Drug Target Mix for the Treatment of Oesophageal Cancer
According to the Compound Type and Developmental Stage of Drug
- Table 69: PKI Drug Target Mix for the Treatment of Ovarian Cancer
According to the Compound Type and Developmental Stage of Drug
- Table 70: PKI Drug Target Mix for the Treatment of Pancreatic Cancer
According to the Compound Type and Developmental Stage of Drug
- Table 71: PKI Drug Target Mix for the Treatment of Peritoneal Cancer
According to the Compound Type and Developmental Stage of Drug
- Table 72: PKI Drug Target Mix for the Treatment of Prostate Cancer
According to the Compound Type and Developmental Stage of Drug
- Table 73: PKI Drug Target Mix for the Treatment of Renal Cancer According
to the Compound Type and Developmental Stage of Drug
- Table 74: PKI Drug Target Mix for the Treatment of Renal Cell Carcinoma
According to the Compound Type and Developmental Stage of Drug
- Table 75: PKI Drug Target Mix for the Treatment of Sarcoma According to
the Compound Type and Developmental Stage of Drug
- Table 76: PKI Drug Target Mix for the Treatment of Leiomyo Sarcoma
According to the Compound Type and Developmental Stage of Drug
- Table 77: PKI Drug Target Mix for the Treatment of Squamous Cell Cancer
According to the Compound Type and Developmental Stage of Drug
- Table 78: PKI Drug Target Mix for the Treatment of Testicular Cancer
According to the Compound Type and Developmental Stage of Drug
- Table 79: PKI Drug Target Mix for the Treatment of Thymoma According to
the Compound Type and Developmental Stage of Drug
- Table 80: PKI Drug Target Mix for the Treatment of Thyroid Cancer
According to the Compound Type and Developmental Stage of Drug
- Table 81: Protein Kinase Inhibitor Drugs with Target Mix and Developmental
Projects by Companies in Australia
- Table 82: Protein Kinase Inhibitor Drugs with Target Mix and Developmental
Projects by Companies in Belgium
- Table 83: Protein Kinase Inhibitor Drugs with Target Mix and Developmental
Projects by Companies in Belgium
- Table 84: Protein Kinase Inhibitor Drugs with Target Mix and Developmental
Projects by Companies in China
- Table 85: Protein Kinase Inhibitor Drugs with Target Mix and Developmental
Projects by Companies in Cuba
- Table 86: Protein Kinase Inhibitor Drugs with Target Mix and Developmental
Projects by Companies in Denmark
- Table 87: Protein Kinase Inhibitor Drugs with Target Mix and Developmental
Projects by Companies in France
- Table 88: Protein Kinase Inhibitor Drugs with Target Mix and Developmental
Projects by Companies in Germany
- Table 89: Protein Kinase Inhibitor Drugs with Target Mix and Developmental
Projects by Companies in India
- Table 90: Protein Kinase Inhibitor Drugs with Target Mix and Developmental
Projects by Companies in India
- Table 91: Protein Kinase Inhibitor Drugs with Target Mix and Developmental
Projects by Companies in Japan
- Table 92: Protein Kinase Inhibitor Drugs with Target Mix and Developmental
Projects by Companies in New Zealand
- Table 93: Protein Kinase Inhibitor Drugs with Target Mix and Developmental
Projects by Companies in South Korea
- Table 94: Protein Kinase Inhibitor Drugs with Target Mix and Developmental
Projects by Companies in Spain
- Table 95: Protein Kinase Inhibitor Drugs with Target Mix and Developmental
Projects by Companies in Switzerland
- Table 96: Protein Kinase Inhibitor Drugs with Target Mix and Developmental
Projects by Companies in United Kingdom
- Table 97: Protein Kinase Inhibitor Drugs with Target Mix and Developmental
Projects by Companies in the USA
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