The Drug Target Atlas of Apoptopic Drugs 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 Introduction __ 18
6 Apoptopic Drug Compound Types and Sub-cellular Localizations of Targets
________ 20
7 The Cancer Genome Project and Apoptopic Drug Targets ___ 26
7.1 Apoptopic Drug Targets Present in the Cancer Gene Census and in the
Catalogue of
Somatic Mutations in Cancer ______ 26
8 Protein Expression Profiles of Apoptopic Drug Targets in Human _______ 30
8.1 Expression in Normal Tissues and Cancer Tissues ___ 30
8.2 Expression in Human Cancer Cell Lines and Primary Cells _____ 31
9 Pathway Analysis of Drug Targets of Apoptopic Drugs ______ 34
10 Protein-Protein Interactions Between Identified Apoptopic Drug Targets _ 49
11 Available Biological Structure Data on Apoptopic Drug Targets ________ 53
12 Drug Target Profiles of Apoptopic Drug Targets in Oncology _ 55
12.1.1 Auxiliary transport protein activity 56
12.1.2 Carboxy-lyase activity _ 57
12.1.3 Catalytic activity _____ 58
12.1.4 Cell adhesion molecule activity ___ 61
12.1.5 Chaperone activity ___ 63
12.1.6 Complement activity __ 65
12.1.7 Cysteine-type peptidase activity __ 67
12.1.8 Cytokine activity _____ 71
12.1.9 DNA topoisomerase activity ______ 73
12.1.10 Glutathione transferase activity ___ 75
12.1.11 Hormone activity ____ 76
12.1.12 Hydrolase activity ____ 77
12.1.13 Intracellular ligand-gated ion channel activity 78
12.1.14 Kinase activity _______ 79
12.1.15 Kinase regulator activity 85
12.1.16 Ligase activity _______ 86
12.1.17 Lipid kinase activity ___ 88
12.1.18 Metallopeptidase activity ________ 89
12.1.19 Molecular function unknown _____ 90
12.1.20 Motor activity _______ 92
12.1.21 Oxidoreductase activity 93
12.1.22 Peptide hormone ____ 94
12.1.23 Peroxidase activity ___ 95
12.1.24 Protein binding ______ 96
12.1.25 Protein serine/threonine kinase activity _____ 98
12.1.26 Protein threonine/tyrosine kinase activity __ 114
12.1.27 Protein-tyrosine kinase activity __ 117
12.1.28 Receptor activity ____ 125
12.1.29 Receptor binding ____ 132
12.1.30 Receptor signaling complex scaffold activity _ 136
12.1.31 Receptor signaling protein serine/threonine kinase activity _______ 140
12.1.32 RNA binding _______ 140
12.1.33 Structural constituent of cytoskeleton _____ 141
12.1.34 Superoxide dismutase activity ___ 142
12.1.35 T cell receptor activity 143
12.1.36 Transcription factor activity _____ 146
12.1.37 Transcription regulator activity __ 155
12.1.38 Transferase activity __ 158
12.1.39 Translation regulator activity ____ 160
12.1.40 Transmembrane receptor activity 162
12.1.41 Transmembrane receptor protein tyrosine kinase activity 163
12.1.42 Transporter activity _ 179
13 Apoptopic Drug Target Mix by Development Stage _______ 181
14 Apoptopic Drug Target Mix by Cancer Indication 188
14.1 Basal Cell Cancer 192
14.2 Biliary Cancer _ 192
14.3 Bladder Cancer 192
14.4 Bone Cancer __ 193
14.5 Brain Cancer __ 194
14.6 Breast Cancer _ 194
14.7 Carcinoid Tumor 197
14.8 Cervical Cancer 197
14.9 Chemotherapy-induced Neutropenia _ 198
14.10 Colorectal Cancer ______ 198
14.11 Endometrial Cancer ____ 200
14.12 Fallopian Tube Cancer __ 200
14.13 Gastrointestinal Cancer _ 201
14.13.1 Gastrointestinal Stomach Cancer _ 201
14.13.2 Gastrointestinal Stromal Cancer _ 202
14.14 Head and Neck Cancer __ 203
14.15 Leukemia ___ 204
14.15.1 Acute Lymphocytic Leukemia ____ 204
14.15.2 Acute Myelogenous Leukemia ___ 206
14.15.3 Chronic Lymphocytic Leukemia __ 207
14.15.4 Chronic Myelogenous Leukemia _ 208
14.16 Liver Cancer _ 209
14.17 Lung Cancer _ 210
14.17.1 Non-Small Cell Lung Cancer _____ 210
14.17.2 Small Cell Lung Cancer 212
14.18 Lymphoma__ 213
14.18.1 B-cell Lymphoma____ 213
14.18.2 Hodgkin's Lymphoma 214
14.18.3 non-Hodgkin's Lymphoma ______ 215
14.18.4 T-cell Lymphoma ____ 216
14.19 Melanoma __ 216
14.20 Mesothelioma 218
14.21 Myelodysplastic Syndrome _______ 219
14.22 Myeloma ___ 220
14.23 Nasopharyngeal Cancer _ 221
14.24 Oesophageal Cancer ____ 221
14.25 Oral Cancer _ 222
14.26 Ovarian Cancer ________ 222
14.27 Pancreatic Cancer ______ 224
14.28 Peritoneal Cancer ______ 225
14.29 Prostate Cancer ________ 226
14.30 Renal Cancer 227
14.31 Sarcoma ____ 229
14.31.1 Leiomyo Sarcoma ___ 229
14.32 Squamous Cell Cancer___ 230
14.33 Testicular Cancer _______ 230
14.34 Thymoma Cancer ______ 230
14.35 Thyroid Cancer ________ 231
15 Apoptopic Drugs and their Targets by Companies ________ 233
15.1 Australia _____ 233
15.2 Canada _______ 234
15.3 China ________ 235
15.4 Denmark _____ 235
15.5 Germany _____ 236
15.6 Israel ________ 236
15.7 Japan ________ 237
15.8 South Korea ___ 237
15.9 Spain ________ 238
15.10 Switzerland _ 238
15.11 Taiwan _____ 239
15.12 United Kingdom _______ 240
15.13 USA _______ 241
16 Disclaimer __ 248
17 Drug Index __ 249
18 Company Index ________ 250
4.1 List of Figures
Figure 1: Distribution of Compound Types Among Apoptopic Drugs .. 20
Figure 2: Primary Sub-cellular Localization of Drug Targets 21
4.2 List of Tables
Table 1: Compound Type Versus Primary and Alternate Localization of Drug Target
... 25
Table 2: Drug Targets of Apoptopic Drugs Present in the Catalogue of Somatic
Mutations in Cancer and in the
Cancer Gene Census ...... 29
Table 3: Available Protein Expression Profiles of Apoptopic Drug Targets .....
33
Table 4: Pathway Summary ......... 34
Table 5: Drug Targets Without any Identified Assigned Pathways ..... 34
Table 6: Pathway Profile According to BioCarta of the Drug Targets Belonging to
Apoptopic Drugs ...... 39
Table 7: Drug Targets Belonging to Apoptopic Pathways According to BioCarta
.......... 42
Table 8: Pathway Profile According to KEGG of the Drug Targets Belonging to
Apoptopic Drugs ........... 43
Table 9: Drug Targets within the Apoptosis Pathway According to KEGG ...... 44
Table 10: Apoptopic Drugs Targeting Major Singaling Pathways ....... 48
Table 11: Protein-Protein Interactions Between Identified Apoptopic Drug Targets
..... 51
Table 12: Targets of Apoptopic Drugs without Protein-Protein Interaction with
other Drug Targets ...... 52
Table 13: Number of Available Biological Structures on Apoptopic Drug Targets
......... 54
Table 14: Overview of Drug Target Profile Themes .. 55
Table 15: Fall Out in Terms of the Number of Drug Target Mixes, Drugs, and
Developmental Projects by
Developmental Stage .. 181
Table 16: Apoptopic Drug Target Mixes by Development .. 187
Table 17: Number of Unique Apoptopic Drug Target Mixes Reported by Cancer
Indication ... 189
Table 18: Apoptopic Drug Target Mix for the Treatment of Basal Cell Cancer
According to the Compound Type
and Developmental Stage of Drug .......... 192
Table 19: Apoptopic Drug Target Mix for the Treatment of Biliary Cancer
According to the Compound Type and
Developmental Stage of Drug ..... 192
Table 20: Apoptopic Drug Target Mix for the Treatment of Bladder Cancer
According to the Compound Type and
Developmental Stage of Drug ..... 193
Table 21: Apoptopic Drug Target Mix for the Treatment of Bone Cancer According
to the Compound Type and
Developmental Stage of Drug ..... 193
Table 22: Apoptopic Drug Target Mix for the Treatment of Brain Cancer According
to the Compound Type and
Developmental Stage of Drug ..... 194
Table 23: Apoptopic Drug Target Mix for the Treatment of Breast Cancer According
to the Compound Type and
Developmental Stage of Drug ..... 197
Table 24: Apoptopic Drug Target Mix for the Treatment of Carcinoid Tumor
According to the Compound Type
and Developmental Stage of Drug .......... 197
Table 25: Apoptopic Drug Target Mix for the Treatment of Cervical Cancer
According to the Compound Type and
Developmental Stage of Drug ..... 198
Table 26: Apoptopic Drug Target Mix for the Treatment of Chemotherapy-induced
Neutropenia According to the
Compound Type and Developmental Stage of Drug .......... 198
Table 27: Apoptopic Drug Target Mix for the Treatment of Colorectal Cancer
According to the Compound Type
and Developmental Stage of Drug .......... 200
Table 28: Apoptopic Drug Target Mix for the Treatment of Endometrial Cancer
According to the Compound Type
and Developmental Stage of Drug .......... 200
Table 29: Apoptopic Drug Target Mix for the Treatment of Fallopian Tube Cancer
According to the Compound
Type and Developmental Stage of Drug .. 201
Table 30: Apoptopic Drug Target Mix for the Treatment of Gastrointestinal Cancer
According to the Compound
Type and Developmental Stage of Drug .. 201
Table 31: Apoptopic Drug Target Mix for the Treatment of Gastrointestinal
Stomach Cancer According to the
Compound Type and Developmental Stage of Drug .......... 202
Table 32: Apoptopic Drug Target Mix for the Treatment of Gastrointestinal
Stromal Cancer According to the
Compound Type and Developmental Stage of Drug .......... 202
Table 33: Apoptopic Drug Target Mix for the Treatment of Head and Neck Cancer
According to the Compound
Type and Developmental Stage of Drug .. 204
Table 34: Apoptopic Drug Target Mix for the Treatment of Leukemia (general)
According to the Compound Type
and Developmental Stage of Drug .......... 204
Table 35: Apoptopic Drug Target Mix for the Treatment of Acute Lymphocytic
Leukemia According to the
Compound Type and Developmental Stage of Drug .......... 205
Table 36: Apoptopic Drug Target Mix for the Treatment of Acute Myelogenous
Leukemia According to the
Compound Type and Developmental Stage of Drug .......... 206
Table 37: Apoptopic Drug Target Mix for the Treatment of Chronic Lymphocytic
Leukemia According to the
Compound Type and Developmental Stage of Drug .......... 207
Table 38: Apoptopic Drug Target Mix for the Treatment of Chronic Myelogenous
Leukemia According to the
Compound Type and Developmental Stage of Drug .......... 209
Table 39: Apoptopic Drug Target Mix for the Treatment of Liver Cancer According
to the Compound Type and
Developmental Stage of Drug ..... 210
Table 40: Apoptopic Drug Target Mix for the Treatment of Lung Cancer (general)
According to the Compound
Type and Developmental Stage of Drug .. 210
Table 41: Apoptopic Drug Target Mix for the Treatment of Non-Small Cell Lung
Cancer According to the
Compound Type and Developmental Stage of Drug .......... 212
Table 42: Apoptopic Drug Target Mix for the Treatment of Small Cell Lung Cancer
According to the Compound
Type and Developmental Stage of Drug .. 213
Table 43: Apoptopic Drug Target Mix for the Treatment of Lymphoma (general)
According to the Compound
Type and Developmental Stage of Drug .. 213
Table 44: Apoptopic Drug Target Mix for the Treatment of B-cell Lymphoma
According to the Compound Type
and Developmental Stage of Drug .......... 214
Table 45: Apoptopic Drug Target Mix for the Treatment of Hodgkin’s Lymphoma
According to the Compound
Type and Developmental Stage of Drug .. 215
Table 46: Apoptopic Drug Target Mix for the Treatment of non-Hodgkin’s Lymphoma
According to the
Compound Type and Developmental Stage of Drug .......... 216
Table 47: Apoptopic Drug Target Mix for the Treatment of T-cell Lymphoma
According to the Compound Type
and Developmental Stage of Drug .......... 216
Table 48: Apoptopic Drug Target Mix for the Treatment of Melanoma According to
the Compound Type and
Developmental Stage of Drug ..... 218
Table 49: Apoptopic Drug Target Mix for the Treatment of Mesothelioma According
to the Compound Type and
Developmental Stage of Drug ..... 218
Table 50: Apoptopic Drug Target Mix for the Treatment of Myelodysplastic
Syndrome According to the
Compound Type and Developmental Stage of Drug .......... 219
Table 51: Apoptopic Drug Target Mix for the Treatment of Myeloma According to
the Compound Type and
Developmental Stage of Drug ..... 221
Table 52: Apoptopic Drug Target Mix for the Treatment of Nasopharyngeal Cancer
According to the Compound
Type and Developmental Stage of Drug .. 221
Table 53: Apoptopic Drug Target Mix for the Treatment of Oesophageal Cancer
According to the Compound
Type and Developmental Stage of Drug .. 222
Table 54: Apoptopic Drug Target Mix for the Treatment of Oral Cancer According
to the Compound Type and
Developmental Stage of Drug ..... 222
Table 55: Apoptopic Drug Target Mix for the Treatment of Ovarian Cancer
According to the Compound Type and
Developmental Stage of Drug ..... 224
Table 56: Apoptopic Drug Target Mix for the Treatment of Pancreatic Cancer
According to the Compound Type
and Developmental Stage of Drug .......... 225
Table 57: Apoptopic Drug Target Mix for the Treatment of Peritoneal Cancer
According to the Compound Type
and Developmental Stage of Drug .......... 225
Table 58: Apoptopic Drug Target Mix for the Treatment of Prostate Cancer
According to the Compound Type
and Developmental Stage of Drug .......... 227
Table 59: Apoptopic Drug Target Mix for the Treatment of Renal Cancer According
to the Compound Type and
Developmental Stage of Drug ..... 229
Table 60: Apoptopic Drug Target Mix for the Treatment of Sarcoma (general)
According to the Compound Type
and Developmental Stage of Drug .......... 229
Table 61: Apoptopic Drug Target Mix for the Treatment of Leiomyo Sarcoma
According to the Compound Type
and Developmental Stage of Drug .......... 230
Table 62: Apoptopic Drug Target Mix for the Treatment of Squamous Cell Cancer
According to the Compound
Type and Developmental Stage of Drug .. 230
Table 63: Apoptopic Drug Target Mix for the Treatment of Testiculat Cancer
According to the Compound Type
and Developmental Stage of Drug .......... 230
Table 64: Apoptopic Drug Target Mix for the Treatment of Thymoma Cancer
According to the Compound Type
and Developmental Stage of Drug .......... 231
Table 65: Apoptopic Drug Target Mix for the Treatment of Thyroid Cancer
According to the Compound Type and
Developmental Stage of Drug ..... 232
Table 66: Apoptopic Drugs with Target Mix and Developmental Projects by
Companies in Australia ... 233
Table 67: Apoptopic Drugs with Target Mix and Developmental Projects by
Companies in Canada ..... 234
Table 68: Apoptopic Drugs with Target Mix and Developmental Projects by
Companies in China ........ 235
Table 69: Apoptopic Drugs with Target Mix and Developmental Projects by
Companies in Denmark ... 235
Table 70: Apoptopic Drugs with Target Mix and Developmental Projects by
Companies in Germany ... 236
Table 71: Apoptopic Drugs with Target Mix and Developmental Projects by
Companies in Israel ......... 236
Table 72: Apoptopic Drugs with Target Mix and Developmental Projects by
Companies in Japan ........ 237
Table 73: Apoptopic Drugs with Target Mix and Developmental Projects by
Companies in South Korea .......... 237
Table 74: Apoptopic Drugs with Target Mix and Developmental Projects by
Companies in Spain ......... 238
Table 75: Apoptopic Drugs with Target Mix and Developmental Projects by
Companies in Switzerland ........... 239
Table 76: Apoptopic Drugs with Target Mix and Developmental Projects by
Companies in Taiwan ...... 239
Table 77: Apoptopic Drugs with Target Mix and Developmental Projects by
Companies in United Kingdom .... 240
Table 78: Apoptopic Drugs with Target Mix and Developmental Projects by Company
in USA . 247