Table 1.
Therapy proposals directed towards different aspects and molecules involved in the pathogenesis of systemic sclerosis.
| Proposed therapy | Target |
|---|---|
| VASCULAR | |
| (i) Bosentan, macitentan | ETA/ETa receptor |
| (ii) Ambrisentan | ETA receptor |
| (iii) Selexipag | IP receptor agonist |
| (iv) Riociguat | GMPc agonist |
| (v) Methyl bardoxolone | Nrf2 and NF-kB |
|
| |
| INFLAMMATION | |
| (i) Anifrolumab | Type I IFN |
| (ii) Sifalimumab, Rontalizumab | Type I IFN |
| (iii) MEDI7734 | Anti-ILT7 |
| (iv) Rituximab | CD20 |
| (v) Basiliximab | IL-2Rα |
| (vi) Efalizumab | LFA1/ICAM-1 |
| (vii) Abatacept | CTLA4 |
| (viii) AIMSPRO( ® ) | αMSH, IL10, CCL2 |
| (ix) Tocilizumab | IL-6R |
| (x) AM095, SAR100842 | LPA1 |
| (xi) TAK242 | TLR4 |
| (xii) Inebilizumab | Anti-CD19 |
|
| |
| FIBROSIS | |
| (i) Imatinib, Dasatinib, Nilotinib | c-Abl, c-Kit, PDGF |
| (ii) CAT-192 | TGFβ1 |
| (iii) GC-1008 | TGFβ1,-β2,-β3 |
| (iv) FG-3019 | CCN2 |
| (v) P144 | TGFβ1 |
| (vi) Anti-Integrin αVβ6 | TGFβ activation |
| (vii) Pirfenidone | TNFα, IL1β, TGFβ |
| (viii) Nintedanib | VEGF, PDGF, FGF |
Note: ET, endothelin; IP, G protein-coupled receptor; cGMP, cyclic guanosine monophosphate; TNF-α, tumor necrosis factor alpha; IL, interleukin; CCR2, chemokine receptor type 2; LFA1, lymphocyte function-associated antigen 1; ICAM-1, intercellular adhesion molecule 1; CTLA-4, cytotoxic T-lymphocyte antigen 4; αMSH, alpha-melanocyte stimulating hormone; CCL2, chemokine (C-C motif) ligand 2; LPA1, lysophosphatidic acid 1; c-Abl, cellular oncogene homologous to Abelson's murine leukemia; c-Kit, proto-oncogene tyrosine kinase; PDGF, platelet-derived growth factor; TGF, transforming growth factor; CCN2, type 2 connective tissue growth factor; VEGF, vascular endothelial growth factor; FGF, fibroblast growth factor; Nrf2: nuclear factor erythroid derived 2-related factor 2; NF-kB: Nuclear factor kappa-light-chain-enhancer of activated B cells.