List of phase II and phase I targets identified by combinations of at least three of the methods A, B, C, and D used in this study Targets marked by an asterisk (*) are innovative targets without a protein subtype as a successful target. Tissue distribution P represents cases where target is distributed in more than five tissues, but the disease-relevant targets are located within blood vessels or cells lining the arteries where they have higher priority to bind drugs.
| Research Target | Identified by Combination | No. of Target-Affiliated Pathways | No. of Human Similarity Proteins outside Target Family | No. of Tissues Target Is Primarily Distributed | Targeted Disease Conditions | Target Exploration Stage (Testing Drug) |
|---|---|---|---|---|---|---|
| C-C chemokine receptor 2* | Combination of A, B, C, D | 1 | 0 | 1 | Rheumatoid arthritis, multiple sclerosis | Phase II (INCB3284), phase I (CCX915) |
| ErbB-4 | Combination of A, B, C, D | 3 | 4 | 2 | Breast cancer | Phase II (CI-1033) |
| Fibroblast growth factor receptor-3 | Combination of A, B, C, D | 3 | 0 | 4 | Solid tumors, multiple myeloma | Phase II (XL999), phase I (CHIR-258) |
| Guanylate cyclase B* | Combination of A, B, C, D | 3 | 0 | 1 | Heart disease | Phase IIa (chimeric natriuretic peptide), preclinical (guanilib) |
| Histone deacetylase 4 | Combination of A, B, C, D | 1 | 1 | P | Basal cell carcinoma, melanoma, cancer | Phase II (avugane, romidepsin, MS-275, PXD101) |
| Neuropeptide Y receptor 2 | Combination of A, B, C, D | 1 | 0 | 4 | Obesity | Phase II (obinepitide) |
| Neuropeptide Y receptor 4 | Combination of A, B, C, D | 1 | 0 | 3 | Schizophrenia, schizoaffective disorders | Phase I/II (TM30339) |
| Toll-like receptor 3 | Combination of A, B, C, D | 1 | 0 | 2 | Human papillomavirus infections | Phase II (HspE7) |
| Fibroblast growth factor receptor-1 | Combination of A, B, C | 5 | 0 | >10 | Coronary heart disease, solid tumors | Phase II (XL999), phase II (fibroblast growth factor-1) |
| Protein kinase C-γ | Combination of A, B, C | 16 | 0 | 4 | Acute myocardial infarction | Phase II (midostaurin), phase I/II (KAI-9803) |
| Tyrosine-protein kinase receptor HTK* | Combination of A, B, C | 1 | 4 | >10 | Lung cancer, solid tumors | Phase II (XL647) |
| Histamine H3 receptor | Combination of A, C, D | 1 | 0 | 4 | Attention-deficit hyperactivity disorder, Alzheimer's disease, schizophrenia | Phase II (cipralisant), phase I (ABT-239) |
| Leukotriene B4 receptor 1* | Combination of A, C, D | 1 | 0 | 4 | Cancer, renal cell carcinoma | Phase II (LY293111), phase I (Biomed 101) |
| Motilin receptor* | Combination of A, C, D | 1 | 0 | 1 | Irritable bowel syndrome, gastrointestinal disorders | Phase IIb (mitemcinal), phase I (KOS-2187) |
| NK-3 receptor* | Combination of A, C, D | 2 | 0 | 1 | Schizophrenia, schizoaffective disorders | Phase IIb (osanetant), phase II (talnetant) |
| Somatostatin receptor type 4 | Combination of A, C, D | 1 | 2 | 3 | Solid tumors | Phase II (CAP-232) |
| Tissue kallikrein-2* | Combination of A, C, D | 1 | 0 | 2 | Atopic dermatitis | Phase II (dermolastin) |
| Toll-like receptor 8 | Combination of A, C, D | 1 | 0 | 5 | Genital warts, systemic lupus erythematosus | Phase II (resiquimod), phase I (CPG 52364) |
| Cell division protein kinase 7 | Combination of A, B, D | 1 | 1 | P | B-cell malignancies | Phase I (SNS-032) |
| Coagulation factor IX* | Combination of A, B, D | 1 | 5 | 1 | Thrombosis, venous thromboembolism | Phase IIa (REG1), phase I completed (TTP889)a |
| Melanocortin receptor* | Combination of A, B, D | 1 | 0 | 3 | Sexual (female) and erectile dysfunction | Phase II b (bremelanotide) |
| Metabotropic glutamate receptor 2/3* | Combination of A, B, D | 1 | 0 | 1 | Psychosis | Phase II (LY2140023, LY354740) |
| Peroxisome proliferator-activated receptor δ | Combination of A, B, D | 3 | 0 | P | Obesity | Phase II (MBX-8025), phase I (KD3010) |
| Serine/threonine-protein kinase Chk2 | Combination of A, B, D | 2 | 0 | 4 | Solid tumors | Phase I (XL844), phase I (UCN-01) |
| Serine/threonine-protein kinase PLK* | Combination of A, B, D | 1 | 1 | P | Pancreatic, prostate and a number of other cancers | Phase I (HMN-214) |
↵ a Howard et al., 2007; Eriksson et al., 2008; Tomillero and Moral, 2008