Summary of clinical development of drug candidates targeting chemokine receptors
See Figs. 8–10 for structures of representative clinical candidates.
Receptor | Company | Compound | Affinity | Indication | Clinical Phase | Status |
---|---|---|---|---|---|---|
nM | ||||||
CCR1 | Schering AG (Berlex) | BX 471 | 1.0 | MS, Psoriasis endometriosis | II | No efficacy |
CCR1 | Millennium | MLN 3701 | MS, Multiple myeloma | II | No longer reported | |
CCR1 | Millennium | MLN 3897 | 2.3 | RA, Multiple myeloma | II | No efficacy in RA |
CCR1 | Pfizer | CP-481,715 | 64 | RA | II | No efficacy |
CCR1 | AstraZeneca | AZD4818 | 5.0 | COPD | II | No efficacy |
CCR1 | ChemoCentryx/GSK | CCX354 | 1.5 | RA | II | Ongoing |
CCR1 | Merck | C-4462 | RA | II | No efficacy | |
CCR1 | Merck | C-6448 | MS | II | No efficacy | |
CCR2 | Millennium | MLN 1202a | RA | II | No efficacy | |
Atherosclerosis, MS | II | Ongoing | ||||
CCR2 | Incyte | INCB8696 | MS, Lupus | I | No longer reported | |
CCR2 | Incyte | INCB3284 | 3.7 | RA, Type II diabetes | II | No longer reported |
CCR2 | ChemoCentryx | CCX915 | MS | I | Terminated | |
CCR2 | ChemoCentryx | CCX140 | 2.3 | Diabetic nephropathy | II | Ongoing |
CCR2 | Merck | MK-0812 | 5.0 | RA, MS | II | No efficacy |
CCR2 | Pfizer | PF-4136309 | Pain | II | No longer reported | |
CCR2 | BMS | BMS-741672 | Diabetic neuropathy | II | Ongoing | |
CCR2 | Johnson & Johnson | JNJ-17166864 | 20.0 | Allergic rhinitis | II | No efficacy |
CCR3 | Pharmaxis | ASM8b | Asthma | II | Ongoing | |
CCR3 | GlaxoSmithKline | GSK766994 | 10.0 | Asthma and allergic rhinitis | II | No efficacy |
CCR3 | Dupont | DPC168 | 2.0 | Asthma | I | Development halted |
CCR3 | BMS | BMS-639623 | 0.3 | Asthma | I | Ongoing |
CCR3 | Novartis | QAP-642 | Allergic rhinitis | I | Development halted | |
CCR3 | AstraZeneca | AZD3778 | 8.1 | Allergic rhinitis | II | No longer reported |
CCR4 | Amgen | KW-0761a | Oncology | II | Ongoing | |
CCR4 | GSK | GSK2239633 | 10.0 | Asthma | I | Ongoing |
CCR5 | Pfizer | UK-427,857 (Maraviroc) | 3.0 | RA | II | No efficacy |
AIDS | Approved | Registered Drug | ||||
CCR5 | Schering-Plough | SCH-C | 2.0 | RA | II | No efficacy |
AIDS | I | Development halted | ||||
CCR5 | Schering-Plough | SCH-D | 0.45 | AIDS | II | Development halted |
CCR5 | GlaxoSmithKline | GW2239633 | 3.0 | AIDS | III | Development halted |
CCR5 | Incyte | INCB9471 | 3.1 | AIDS | II | Development halted |
CCR5 | Progenics | Pro 140a | AIDS | II | Ongoing | |
CCR5 | Tobira | TAK652 (cenicroviroc) | 3.1e | AIDS | II | Ongoing |
CCR5 | AstraZeneca | AZD5672 | 0.26 | RA | II | No efficacy |
CCR5 | Novartis | NIBR-6465 | 0.8 | AIDS | I | Ongoing |
CCR5 | Sangamo | SB-728c | AIDS | II | Ongoing | |
CCR5 | HGS | HGS004a | AIDS | I | Ongoing | |
CCR9 | ChemoCentryx/GSK | CCX282/vercirnon | 6.0 | IBD, Crohn’s | III | Terminated |
CXCR1/ CXCR2 | Schering-Plough | SCH 527123 | 3.9 | COPD | II | Ongoing |
0.049 | ||||||
CXCR1/ CXCR2 | Dompé | Reparixin | 1.0 (CXCR1) | Pancreatic islet transplantation | III | Ongoing |
100 (CXCR2) | ||||||
CXCR2 | GlaxoSmithKline | SB-656933 | 5.1 | COPD, Cystic fibrosis | I | Ongoing |
CXCR2 | GlaxoSmithKline | GSK-1325756B | COPD? | I | Ongoing | |
CXCR2 | AstraZeneca | AZD-5069 | Bronchiectasis | II | Ongoing | |
CXCR3 | Amgen | AMG487 | 8.0 | Psoriasis | II | No efficacy |
CXCR4 | Genzyme/Sanofi-Aventis | Plerixafor (AMD3100) | 74 | Stem cell mobilization for transplantation in cancer (MM, Non-Hodgkins lymphoma) | Approved | Registered Drug |
CXCR4 | TaiGen | Burixafor | Stem cell transplantation | II | Ongoing | |
CXCR4 | Polyphor | POL6326 | Stem cell transplantation | II | Ongoing | |
CXCR4 | Medarex | MDX-1338a | Multiple myeloma | I | Ongoing | |
CXCR4 | Biokine | BKT140d | Stem cell transplantation | I | Ongoing |