Table 1.
Protein targets and their agents in rheumatoid arthritis.
| Targets | Agents | Phases | References |
|---|---|---|---|
| Cytokines | |||
| TNF | Adalimumab | Marketed | (7) |
| Infliximab | Marketed | (7) | |
| Etanercept | Marketed | (7) | |
| Certolizumab | Marketed | (7) | |
| Golimumab | Marketed | (7) | |
| IL-1R | Anakinra | Marketed | (7) |
| IL-1 | Canakinumab | Marketed | (7) |
| Gevokizumab | Marketed | (7) | |
| Rilonacept | Terminated | Clinicaltrials.gov | |
| IL-6R | Tocilizumab | Marketed | (7) |
| IL-6a | Sarilumab | Marketed | (7) |
| Clazakizumab | Marketed | (7) | |
| Olokizumab | Marketed | (7) | |
| Sirukumab | Marketed | (7) | |
| Il-2 | MEDI5117 | Terminated | Clinicaltrials.gov |
| IL-10 | Dekavil | Phase 1 | (22) |
| IL-15 | AMG-714 | Phase 2 | (23) |
| IL-18 | rhIL-18BP | Phase 1 | (24) |
| IL-17 | Secukinumab | Phase 3 | (25) |
| Ixekizumab | Phase 2 | (26) | |
| IL-17R | Brodalumab | Terminated | Clinicaltrials.gov |
| IFN-γ | Fontolizumab | Terminated | Clinicaltrials.gov |
| Chemokines | |||
| CCL2 | p8A MCP-1 | Animal study | (27) |
| ABN912 | Phase 1 | (28) | |
| CCR9 | CCX8037 | Animal study | (29) |
| CX3CL1 | E6011 | Phase 1 | (30) |
| CCR1 | J−113863 | Animal study | (31) |
| BX147 | Animal study | (32) | |
| BAY86-5047 | Phase 2 | Clinicaltrials.gov | |
| ZK811752 | Phase 2 | Clinicaltrials.gov | |
| CCX354 | Phase 2 | (33) | |
| BMS-817399 | Phase 2 | Clinicaltrials.gov | |
| CCR2 | MK−0812 | Phase 2 | Clinicaltrials.gov |
| MC−21 | Animal study | (34) | |
| MLN1202 | Phase 2a | (35) | |
| CCR5 | SCH−X82 | Phase 2 | (32) |
| Met-RANTES | Phase 2 | (36) | |
| AZD5672 | Phase 2 | (37) | |
| Maraviroc | Terminated | (38) | |
| SCH351125 | Phase 1b | (39) | |
| Other proteins | |||
| TLR4 | NI-0101 | Phase 2 | Clinicaltrials.gov |
| GRK2 | Paroxetine | Phase 2 | Clinicaltrials.gov |
| MEK | ARRY-162 | Phase 2 | Clinicaltrials.gov |
| MMP-9 | Andecaliximab | Phase 2 | (40) |
| CD3 | Otelixizumab | Phase 1 | (41) |
| CD80 | Abatacept | Marketed | (42) |
| BTK | ICP-022 | Phase 1 | Clinicaltrials.gov |
| CC-292 | Phase 2 | (43) | |
| HM71224 | Phase 1 | Clinicaltrials.gov | |
| Il-23 | STA 5326 mesylate | Phase 2 | (44) |
| Guselkumab | Terminated | Clinicaltrials.gov | |
| GM-CSF | Otilimab | Phase 3 | (45) |
| Gimsilumab | Phase 1 | (45) | |
| Namilumab | Phase 2 | (45) | |
| Mavrilimumab | Phase 2 | (45) | |
| Lenzilumab | Terminated | Clinicaltrials.gov | |
| Chemokines | |||
| CXCL10 | MDX−1100 | Phase 2 | (25) |
| CXCL12 | 30D8 | Animal study | (46) |
| CXCL13 | mAb470 | Animal study | (47) |
| CXCL16 | IgG1 12-81 | Animal study | (48) |
| CXCR1/2 | Repertaxin | Animal study | (49) |
| DF2162 | Animal study | (50) | |
| CXCR3 | SCH546738 | Animal study | (51) |
| AMG487 | Animal study | (52) | |
| JN-2 | Animal study | (53) | |
| CXCR4 | Plerixafor | Animal study | (54) |
| T140 | Animal study | (55) | |
| AMD3100 | Animal study | (56) | |
| CXCR7 | CCX733 | Animal study | (56) |
| CCR7 | 8H3-16A12 | Animal study | (57) |
| Other proteins | |||
| JAK | Tofacitinib | Approved | (58) |
| Baricitinib | Approved | (58) | |
| Filgotinib | Phase 3 | Clinicaltrials.gov | |
| Upadacitinib | Approved | (58) | |
| Peficitinib | Phase 3 | (58) | |
| Ruxolitinib | Phase 2 | Clinicaltrials.gov | |
| Itacitinib | Phase 2 | Clinicaltrials.gov | |
| Tasocitinib | Phase 2 | Clinicaltrials.gov | |
| INCB018424 | Phase 2 | Clinicaltrials.gov | |
| VX-509 | Phase 3 | Clinicaltrials.gov | |
| p38 MAPK | RO4402257 | Phase 2 | Clinicaltrials.gov |
| PH-797804 | Phase 2 | Clinicaltrials.gov | |
| VX-702 | Phase 2 | Clinicaltrials.gov | |
| BMS-582949 | Phase 2 | Clinicaltrials.gov | |
| ARRY-371797 | Phase 1 | Clinicaltrials.gov | |
| SCIO-469 | Phase 2 | Clinicaltrials.gov | |
| SB-681323 | Phase 2 | Clinicaltrials.gov | |
| IRAK-4 | PF-06650833 | Phase 2 | (59) |
| BAY1834845 | Phase 1 | (59) | |
| BAY1830839 | Phase 1 | (59) | |
| CA-4948 | Phase 2 | (59) | |
| CD20 | Rituximab | Phase 3 | (60) |
| Ocrelizumab | Terminated | Clinicaltrials.gov | |
| Ofatumumab | Phase 3 | Clinicaltrials.gov | |
| CD11a | Efalizumab | Phase 2 | Clinicaltrials.gov |
| BTK | M2951 | Phase 2 | Clinicaltrials.gov |
| GS-4059 | Phase 1 | Clinicaltrials.gov | |
| CD19 | MDX-1342 | Phase 1 | Clinicaltrials.gov |
TNF, tumor necrosis factor; IL-1R, IL-1β, IL-6R, IL-6a, IL-2, IL-10, IL-15, IL-17, IL-17R, IL-18, IL-23, interleukin (IL)-1 receptor, -1 beta, -6 receptor, -6 antibody, -2, -10, -15, -17, -17 receptor, -18, -23, respectively; TGF-β, transforming growth factor-beta; IFN-γ, interferon-gamma; GM-CSF, granulocyte-macrophage colony stimulating factor; GM-CSFR, granulocyte-macrophage colony stimulating factor receptor; Ab, antibody; JAK, Janus kinase; IRAK-4, interleukin (IL)-1 receptor associated kinase 4; p38 MAPK, mitogen-activated protein kinases; MMP-9, matrix metalloproteinase 9; CD20, CD80, CD3, CD11a, CD19, cluster of differentiation (CD)-20, -80, -3, -11a, -19, respectively; GRK2, G protein-coupled receptor kinase 2; BMP9, bone morphogenetic protein 9; TLR4, toll like receptor 4; MEK, mitogen-activated protein kinase; BTK, Bruton’s tyrosine kinase; CXCL10, CXCL12, CXCL13, CXCL16, CXC motif ligand-10, -12, -13, -16; CXCR1/2, CXCR3, CXCR4, CXCR7, CXC motif receptor-1/2, -3, -4, -7; CCL2, CC motif ligand 2; CCR1, CCR2, CCR5, CCR7, CCR9, CC motif receptor-1, -2, -5, -7, -9; CX3CL1, CX3C ligand 1.