Target Atlas: Competitive Insights to Anti-Angiogenic Drug R&D in Oncology

1 Executive Summary _ 3
2 About Cancer Highlights ______ 5
3 Methodologies _____ 7
4 Table of Contents ___ 9
4.1 List of Figures ______ 13
4.2 List of Tables _______ 13
5 How to Use this Report ______ 18
6 Anti-Angiogenic Drug Compound Types and Sub-cellular Localizations of Targets ___ 20
7 The Cancer Genome Project and Angiogenesis Drug Targets __ 26
7.1 Anti-Angiogenic Drug Targets Present in the Cancer Gene Census and in the Catalogue of
Somatic Mutations in Cancer  26
8 Protein Expression Profiles of Anti-Angiogenic Drug Targets in Human __ 29
8.1 Expression in Normal Tissues and Cancer Tissues  29
8.2 Expression in Human Cancer Cell Lines and Primary Cells __ 30
9 Pathway Analysis of Anti-Angiogenic Drugs __ 33
10 Protein-Protein Interactions Among Identified Anti-Angiogenic Drug Targets ______ 62
11 Available Biological Structure Data on Anti-Angiogenic Drug Targets ___ 66
12 Drug Target Profiles of Anti-angiogenesis Drug Targets in Oncology ____ 68
12.1.1 Carboxy-Lyase Activity ____ 70
12.1.2 Catalytic Activity  70
12.1.3 Cell Adhesion Molecule Activity ______ 72
12.1.4 Chaperone Activity _______ 75
12.1.5 Cofactor Binding  76
12.1.6 Cysteine-Type Peptidase Activity _____ 77
12.1.7 Cytokine Activity  78
12.1.8 DNA Topoisomerase Activity ________ 80
12.1.9 DNA-Directed DNA Polymerase Activity ___ 81
10 Cancer Highlights No 7 Vol 7 2008| BioSeeker Group AB © 2008
12.1.10 Extracellular Matrix Structural Constituent _ 82
12.1.11 G-Protein Coupled Receptor Activity __ 83
12.1.12 Growth Factor Activity ____ 84
12.1.13 GTPase Activity _ 87
12.1.14 Hydrolase Activity ________ 88
12.1.15 Kinase Activity __ 88
12.1.16 Lipid Kinase Activity ______ 89
12.1.17 Metallopeptidase Activity __ 90
12.1.18 Molecular Function Unknown _______ 96
12.1.19 Motor Activity __ 97
12.1.20 Peptidase Activity ________ 97
12.1.21 Protease Inhibitor Activity _ 99
12.1.22 Protein Serine/Threonine Kinase Activity _ 100
12.1.23 Protein-Tyrosine Kinase Activity _____ 109
12.1.24 Receptor Activity ________ 111
12.1.25 Receptor Binding ________ 119
12.1.26 Serine-Type Peptidase Activity ______ 121
12.1.27 Structural Constituent of Cytoskeleton ___ 122
12.1.28 Superoxide Dismutase Activity ______ 123
12.1.29 Transcription Factor Activity _______ 124
12.1.30 Transcription Regulator Activity _____ 126
12.1.31 Translation Regulator Activity ______ 129
12.1.32 Transmembrane Receptor Activity __ 131
12.1.33 Transmembrane Receptor Protein Tyrosine Kinase Activity _____ 132
12.1.34 Transporter Activity _____ 150
13 The Drug-Protein Interactome of Anti-Angiogenic Drugs  151
14 The Progression and Maturity of Anti-Angiogenic Drug Target Combinations _____ 155
14.1 Target Profiles of Anti-Angiogenic Drugs on the Market __ 155
14.2 New Anti-Angiogenic Drug Target Combinations in Phase III Clinical Development ___ 156
14.3 New Anti-Angiogenic Drug Target Combinations in Phase II Clinical Development ___ 157
14.4 New Anti-Angiogenic Drug Target Combinations Phase I Clinical Development ______ 158
14.5 New Anti-Angiogenic Drug Target Combinations in Preclinical Development ________ 159
14.6 Development Profiles of All Identified Anti-Angiogenic Drug Target Combinations ___ 161
15 Anti-Angiogenic Drug Target Mix by Cancer Indication _ 168
15.1 Adrenal Cancer ____ 170
15.2 Biliary Cancer _____ 170
15.3 Bladder Cancer ____ 171
15.4 Bone Cancer ______ 171
15.5 Brain Cancer ______ 172
15.6 Breast Cancer _____ 173
15.7 Carcinoid Tumor ___ 176
15.8 Cervical Cancer ____ 176
15.9 Chemotherapy-Induced Infection __ 177
15.10 Colorectal Cancer  177
15.11 Endometrial Cancer _______ 179
15.12 Fallopian Tube Cancer _____ 180
15.13 Gastrointestinal Cancer ____ 180
15.13.1 Gastrointestinal Stomach Cancer ____ 181
15.13.2 Gastrointestinal Stromal Cancer ____ 182
15.14 Head and Neck Cancer _____ 183
15.15 Leukemia _______ 184
15.15.1 Acute Lymphocytic Leukemia _______ 184
15.15.2 Acute Myelogenous Leukemia ______ 184
15.15.3 Chronic Lymphocytic Leukemia _____ 185
15.15.4 Chronic Myelogenous Leukemia ____ 185
15.16 Liver Cancer _____ 186
15.17 Lung Cancer _____ 187
15.17.1 Non-Small Cell Lung Cancer ________ 188
15.17.2 Small Cell Lung Cancer ___ 191
15.18 Lymphoma______ 192
15.18.1 B-Cell Lymphoma _______ 192
15.18.2 Hodgkin’s Lymphoma ____ 193
15.18.3 Non-Hodgkin’s Lymphoma  193
15.19 Melanoma ______ 194
15.20 Mesothelioma ___ 196
15.21 Myelodysplastic Syndrome _ 196
15.22 Myeloma _______ 196
15.23 Nasopharyngeal Cancer ____ 197
15.24 Oesophageal Cancer _______ 198
15.25 Ovarian Cancer __ 199
15.26 Pancreatic Cancer  200
15.27 Peritoneal Cancer  202
15.28 Prostate Cancer __ 202
15.29 Renal Cancer ____ 204
15.30 Sarcoma ________ 207
15.30.1 Leiomyo Sarcoma _______ 208
15.31 Squamous Cell Cancer______ 209
15.32 Thyroid Cancer __ 209
16 Anti-Angiogenic Drugs and Their Targets by Companies  211
16.1 Australia  211
16.2 Austria __ 211
16.3 Belgium _ 212
16.4 Canada __ 212
16.5 China ___ 212
16.6 Denmark  213
16.7 France __ 213
16.8 Germany  213
16.9 Israel ___ 214
16.10 Japan _ 215
16.11 Netherlands _____ 215
16.12 South Korea _____ 215
16.13 Spain _ 216
16.14 Sweden ________ 216
16.15 Switzerland _____ 216
16.16 United Kingdom _ 218
16.17 USA __ 220
17 Disclaimer ______ 225
18 Drug Index ______ 226
19 Company Index __ 229
4.1 List of Figures
Figure 1: Distribution of Compound Types Among Anti-Angiogenic Drugs ..... 20
Figure 2: Primary Sub-cellular Localization of Drug Targets  21
Figure 3: Visualization of Protein-Protein Interactions Among Anti-Angiogenic Drug Targets .. 65
Figure 4: The Drug-Protein Interactome of Anti-Angiogenic Drugs . 153
Figure 5: Direct Head-to-Head Targeting Interactome of Anti-Angiogenic Drugs ...... 154
4.2 List of Tables
Table 1: Compound Type Versus Primary and Alternate Localization of Drug Target .. 25
Table 2: Drug Targets of Anti-Angiogenic Drugs Present in the Catalogue of Somatic Mutations in Cancer and in
the Cancer Gene Census  28
Table 3: Available Protein Expression Profiles of Anti-Angiogenic Drug Targets .......... 32
Table 4: Pathway Summary ........ 33
Table 5: Drug Targets Without any Identified Assigned Pathways .... 33
Table 6: Pathway Profile According to BioCarta of the Anti-Angiogenic Drug Targets . 45
Table 7: Pathway Profile According to KEGG of the Anti-Angiogenic Drug Targets ...... 58
Table 8: Anti-Angiogenic Drugs Targeting Major Singaling Pathways ........... 61
Table 9: Protein-Protein Interactions Among Anti-Angiogenic Drug Targets . 64
Table 10: Number of Available Biological Structures on Anti-Angiogenic Drug Targets ............ 67
Table 11: Overview of Drug Target Profile Themes . 68
Table 12: Drug-Protein Clusters in the Anti-Angiogenic Interactome ........... 151
Table 13: Fall Out in Terms of the Total Number of Drug Target Mixes, Drugs, Developmental Projects, and the
Presence of New Drug Target Mixes by Developmental Stage ........ 155
Table 14: Target Profiles of Anti-Angiogenic Drugs on the Market . 156
Table 15: New Anti-Angiogenic Drug Target Combinations in Phase III Clinical Development  156
Table 16: New Anti-Angiogenic Drug Target Combinations in Phase II Clinical Development . 158
Table 17 New Anti-Angiogenic Drug Target Combinations Phase I Clinical Development ....... 159
Table 18: New Anti-Angiogenic Drug Target Combinations in Preclinical Development ......... 161
Table 19: The Progression, Maturity and Comptitive Comparison of Anti-Angiogenic Drug Target Mixes in
Development .. 167
Table 20: Number of Unique Anti-angiogenic Drug Target Mixes Reported by Cancer Indication ........ 169
Table 21: The Competitive Situation on Bevacizumab (Avastin) ...... 170
Table 22: Anti-angiogenic Drug Target Mix for the Treatment of Adrenal Cancer According to the Compound
Type and Developmental Stage of Drug .. 170
Table 23: Anti-angiogenic Drug Target Mix for the Treatment of Biliary Cancer According to the Compound Type
and Developmental Stage of Drug .......... 171
Table 24: Anti-angiogenic Drug Target Mix for the Treatment of Bladder Cancer According to the Compound
Type and Developmental Stage of Drug .. 171
Table 25: Anti-angiogenic Drug Target Mix for the Treatment of Bone Cancer According to the Compound Type
and Developmental Stage of Drug .......... 171
Table 26: Anti-angiogenic Drug Target Mix for the Treatment of Brain Cancer According to the Compound Type
and Developmental Stage of Drug .......... 173
Table 27: Anti-angiogenic Drug Target Mix for the Treatment of Breast Cancer According to the Compound Type
and Developmental Stage of Drug .......... 176
Table 28: Anti-angiogenic Drug Target Mix for the Treatment of Carcinoid Tumor According to the Compound
Type and Developmental Stage of Drug .. 176
Table 29: Anti-angiogenic Drug Target Mix for the Treatment of Cervical Cancer According to the Compound
Type and Developmental Stage of Drug .. 176
Table 30: Anti-angiogenic Drug Target Mix for the Treatment of Chemotherapy-induced Infection According to
the Compound Type and Developmental Stage of Drug .... 177
Table 31: Anti-angiogenic Drug Target Mix for the Treatment of Colorectal Cancer According to the Compound
Type and Developmental Stage of Drug .. 179
Table 32: Anti-angiogenic Drug Target Mix for the Treatment of Endometrial Cancer According to the
Compound Type and Developmental Stage of Drug .......... 180
Table 33: Anti-angiogenic Drug Target Mix for the Treatment of Fallopian Tube Cancer According to the
Compound Type and Developmental Stage of Drug .......... 180
Table 34: Anti-angiogenic Drug Target Mix for the Treatment of Gastrointestinal Cancer (General) According to
the Compound Type and Developmental Stage of Drug .... 181
Table 35: Anti-angiogenic Drug Target Mix for the Treatment of Gastrointestinal Stomach Cancer According to
the Compound Type and Developmental Stage of Drug .... 182
Table 36: Anti-angiogenic Drug Target Mix for the Treatment of Gastrointestinal Stromal Cancer According to
the Compound Type and Developmental Stage of Drug .... 182
Table 37: Anti-angiogenic Drug Target Mix for the Treatment of Head and Neck Cancer According to the
Compound Type and Developmental Stage of Drug .......... 183
Table 38: Anti-angiogenic Drug Target Mix for the Treatment of Leukemia (General) According to the Compound
Type and Developmental Stage of Drug .. 184
Table 39: Anti-angiogenic Drug Target Mix for the Treatment of Acute Lymphocytic Leukemia According to the
Compound Type and Developmental Stage of Drug .......... 184
Table 40: Anti-angiogenic Drug Target Mix for the Treatment of Acute Myelogenous Leukemia According to the
Compound Type and Developmental Stage of Drug .......... 185
Table 41: Anti-angiogenic Drug Target Mix for the Treatment of Chronic Lymphocytic Leukemia Cancer
According to the Compound Type and Developmental Stage of Drug .......... 185
Table 42: Anti-angiogenic Drug Target Mix for the Treatment of Chronic Myelogenous Leukemia Cancer
According to the Compound Type and Developmental Stage of Drug .......... 186
Table 43: Anti-angiogenic Drug Target Mix for the Treatment of Liver Cancer According to the Compound Type
and Developmental Stage of Drug .......... 187
Table 44: Anti-angiogenic Drug Target Mix for the Treatment of Lung Cancer (General) According to the
Compound Type and Developmental Stage of Drug .......... 188
Table 45: Anti-angiogenic Drug Target Mix for the Treatment of Non-Small Cell Lung Cancer According to the
Compound Type and Developmental Stage of Drug .......... 190
Table 46: Anti-angiogenic Drug Target Mix for the Treatment of Small Cell Lung Cancer According to the
Compound Type and Developmental Stage of Drug .......... 192
Table 47: Anti-angiogenic Drug Target Mix for the Treatment of Lymphoma (General) According to the
Compound Type and Developmental Stage of Drug .......... 192
Table 48: Anti-angiogenic Drug Target Mix for the Treatment of B-Cell Lymphoma According to the Compound
Type and Developmental Stage of Drug .. 193
Table 49: Anti-angiogenic Drug Target Mix for the Treatment of Hodgkin’s Lymphoma According to the
Compound Type and Developmental Stage of Drug .......... 193
Table 50: Anti-angiogenic Drug Target Mix for the Treatment of Non-Hodgkin’s Lymphoma According to the
Compound Type and Developmental Stage of Drug .......... 194
Table 51: Anti-angiogenic Drug Target Mix for the Treatment of Melanoma According to the Compound Type
and Developmental Stage of Drug .......... 196
Table 52: Anti-angiogenic Drug Target Mix for the Treatment of Mesothelioma According to the Compound
Type and Developmental Stage of Drug .. 196
Table 53: Anti-angiogenic Drug Target Mix for the Treatment of Myelodysplastic Syndrome According to the
Compound Type and Developmental Stage of Drug .......... 196
Table 54: Anti-angiogenic Drug Target Mix for the Treatment of Myeloma According to the Compound Type and
Developmental Stage of Drug .... 197
Table 55: Anti-angiogenic Drug Target Mix for the Treatment of Nasopharyngeal Cancer According to the
Compound Type and Developmental Stage of Drug .......... 198
Table 56: Anti-angiogenic Drug Target Mix for the Treatment of Oesophageal Cancer According to the
Compound Type and Developmental Stage of Drug .......... 198
Table 57: Anti-angiogenic Drug Target Mix for the Treatment of Ovarian Cancer According to the Compound
Type and Developmental Stage of Drug .. 200
Table 58: Anti-angiogenic Drug Target Mix for the Treatment of Pancreatic Cancer According to the Compound
Type and Developmental Stage of Drug .. 201
Table 59: Anti-angiogenic Drug Target Mix for the Treatment of Peritoneal Cancer According to the Compound
Type and Developmental Stage of Drug .. 202
Table 60: Anti-angiogenic Drug Target Mix for the Treatment of Prostate Cancer According to the Compound
Type and Developmental Stage of Drug .. 204
Table 61: Anti-angiogenic Drug Target Mix for the Treatment of Renal Cancer According to the Compound Type
and Developmental Stage of Drug .......... 207
Table 62: Anti-angiogenic Drug Target Mix for the Treatment of Sarcoma (General) According to the Compound
Type and Developmental Stage of Drug .. 208
Table 63: Anti-angiogenic Drug Target Mix for the Treatment of Leiomyo Sarcoma According to the Compound
Type and Developmental Stage of Drug .. 209
Table 64: Anti-angiogenic Drug Target Mix for the Treatment of Squamous Cell Cancer According to the
Compound Type and Developmental Stage of Drug .......... 209
Table 65: Anti-angiogenic Drug Target Mix for the Treatment of Thyroid Cancer According to the Compound
Type and Developmental Stage of Drug .. 210
Table 66: Anti-angiogenic drugs with Target Mix and Developmental Projects by Companies in Australia ...... 211
Table 67: Anti-angiogenic drugs with Target Mix and Developmental Projects by Companies in Austria ......... 211
Table 68: Anti-angiogenic drugs with Target Mix and Developmental Projects by Companies in Belgium ........ 212
Table 69: Anti-angiogenic drugs with Target Mix and Developmental Projects by Companies in Canada ......... 212
Table 70: Anti-angiogenic drugs with Target Mix and Developmental Projects by Companies in China ............ 212
Table 71: Anti-angiogenic drugs with Target Mix and Developmental Projects by Companies in Denmark ...... 213
Table 72: Anti-angiogenic drugs with Target Mix and Developmental Projects by Companies in France .......... 213
Table 73; Anti-angiogenic drugs with Target Mix and Developmental Projects by Companies in Germany ...... 214
Table 74: Anti-angiogenic drugs with Target Mix and Developmental Projects by Companies in Israel ............ 214
Table 75: Anti-angiogenic drugs with Target Mix and Developmental Projects by Companies in Japan ........... 215
Table 76: Anti-angiogenic drugs with Target Mix and Developmental Projects by Companies in the Netherlands
......... 215
Table 77: Anti-angiogenic drugs with Target Mix and Developmental Projects by Companies in South Korea . 216
Table 78: Anti-angiogenic drugs with Target Mix and Developmental Projects by Companies in South Korea . 216
Table 79: Anti-angiogenic drugs with Target Mix and Developmental Projects by Companies in Sweden ........ 216
Table 80: Anti-angiogenic drugs with Target Mix and Developmental Projects by Companies in Switzerland .. 217
Table 81: Anti-angiogenic drugs with Target Mix and Developmental Projects by Companies in United Kingdom
......... 218
Table 82: Anti-angiogenic drugs with Target Mix and Developmental Projects by Companies in USA . 224