Systemic Sclerosis Pathogenesis and Emerging Therapies, beyond the Fibroblast

Table 1

Therapy proposals directed towards different aspects and molecules involved in the pathogenesis of systemic sclerosis.

Proposed therapy	Target
VASCULAR
(i) Bosentan, macitentan	receptor
(ii) Ambrisentan	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)	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.