Table 1.
Summary of research on PDGF/PDGFR-related pharmaceutical targets.
| Drug name | Drug type | Target | Model | Main effect | Source |
|---|---|---|---|---|---|
| Nilotinib | Tyrosine kinase inhibitor | PDGFR | Murine model of asthma remodelling (Ovalbumin sensitization) |
Suppression of ASM fibrotic changes, inhibition of collagen deposition TGF-β1 in BAL reduction |
(Kang et al., 2016) |
| Reduced number of total cells, macrophages, eosinophils, and neutrophils in the BAL fluid AHR – decreased Peth value Decreased collagen (hydroxyproline) deposition Inhbition of fibroblast proliferation Inhibition of ASM area increase Decrease in expression of PDGFRβ mRNA |
(Rhee et al., 2014) | ||||
| Imatinib | Tyrosine kinase inhibitor | PDGFR; (also: ABL, c-kit) |
Murine model of asthma remodelling (Ovalbumin sensitization) |
Imatinib therapy in OVA-challenged mice significantly reduced the total number of cells, eosinophils and neutrophils in BAL fluid AHR – decreased Peth value Decreased collagen (hydroxyproline) deposition Reduced area of the ASM Layer TGF-β1 in BAL reduction SCF expression reduction |
(Rhee et al., 2011) |
| Randomized, double-blind, placebo-controlled, 24-week trial of imatinib in 62 patients with poorly controlled severe asthma | reduced airway hyperresponsiveness to a greater extent than did placebo increase in methacholine PC20 was more than 1 doubling dose Decrease in mast-cell counts, and tryptase release |
(Cahill et al., 2017) | |||
| Masitinib | Tyrosine kinase inhibitor | PDGFR; (also: c-kit, Lyn, FGFR3) |
Feline model of asthma (Bermuda grass allergen sensitization) |
Reduced BAL eosinophilia and total protein | (Lee-Fowler et al., 2012) |
| A 16-week randomized, dose-ranging (3, 4.5, and 6 mg/kg/day), placebo-controlled study in 44 patients | ACQ score improvement (reduction by 0.99 unit at week 16 vs 0.43 in the placebo arm) | (Humbert et al., 2009) | |||
| Sunitinib | Tyrosine kinase inhibitor | All PDGFRs; (also: all VEGFRs, c-kit, RET, CD114, CD135) |
Murine model of asthma remodelling (Ovalbumin sensitization) |
Supressed eosinophilic airway inflammation, AHR and airway remodeling in a murine chronic asthma model, at least partially via PDGFR inhibition. It also reduced the total serum IgE and BALF Th2 cytokines | (Huang et al., 2009) |
| Murine model of asthma (House dust mite-induced allergic asthma) | Reduced airway hyperreactivity | (Lam et al., 2010) | |||
| WAY-200070; FERB-033;, DiarylPropio-Nitrile | ERβ agonists | ERβ | In vitro – human ASM cells (asthmatic and non-asthmatic_ | Suppression of PDGF-stimulated ASM cell proliferation | (Ambhore et al., 2018) |
| Dimethylfumarate (DMF) | Increase in HO-1 expression | Supression of PDGF-BB-induced ASM proliferation | In vitro – human ASM cells | DMF down-regulates PDGF-BB induced proliferation of ASMC through a GSH and p38 MAPK dependent induction of HO-1 | (Seidel et al., 2010) |
| Baicalin | Flavone glycoside | Unknown (Possibly suppressing the MAPK signaling pathway) |
In vitro – rat ASM cells | Inhibition of PDGF-induced ASM cell proliferation, cell migration | (Yang et al., 2015) |
| CC10 (Clara cell 10 kDa protein) | Recombinant Protein | Unknown (Possibly downregulation of cyclin D1 expression) |
In vitro – rat ASM cells | Inhibition of PDGF-BB-Induced ASMCs Proliferation and suppression of PDGF-BB-induced ASMCs migration |
(Wei et al., 2013) |
| Iptakalim | lipophilic para-amino compound | ATP-sensitive potassium channel opener | In vitro – human ASM cells | Inhibition of PDGF-BB-induced human ASMCs proliferation and migration; Blockage of PDGF-BB-stimulated S phase entry of human ASMCs |
(Liu et al., 2015) |
| S100A8 | Recombinant protein | Unknown (Possibly mediation by RAGE membrane receptor, TLR4 and CD36) | In vitro – rat ASM cells | Inhibition of the PDGF-induced proliferation of ASM | (Xu et al., 2017) |
| inhibits the PDGF-induced migration of ASM | (Xu et al., 2016) |