Table 2.
Therapeutic interventions targeting cytoskeletal mechanics in asthma—Implications for fluidization and solidification
| Drug/compound | Target | Fluidization–solidification mechanism(s) | Comments | References |
|---|---|---|---|---|
| Y16 | ARHGEF12 | Actin polymerization | Attenuated IL-17 induced bronchial ring hypercontraction | (53) |
| Fasudil/hyroxyfasudil | ROCK | Reduced MYPT1 phosphorylation | Decreased AHR in mouse models and PCLS; anti-inflammatory | (54) |
| TSG12/TSG1180 | Transgelin-2 | MYPT1 dephosphorylation; RhoA, ezrin phosphorylation | Elicit bronchodilation and reduce AHR in mouse models | (59, 60) |
| Volasertib (BI6727) | Plk1 | Actin polymerization | Relaxation of mouse bronchial rings; reduced HDM associated AHR; Phase III clinical trials for cancer | (77) |
| Imatinib | c-Abl | Actin polymerization | Reduced AHR in short term RDBPC trial of patients with severe asthma | (81) |
| FR900359 | Gαq | Ca2+ flux, MLC phosphorylation | Decreased AHR in several animal models of asthma | (107) |
| R59949 | diacylglycerol kinase (DGKζ) | Ca2+ flux (PLCβ) | Decreased AHR in mouse models and PCLS; anti-inflammatory | (108, 109) |
| Pitavastatin, atorvastatin | RhoA | Inhibits MLC phosphorylation, actin polymerization | Reduces AHR in mice and PCLS contraction; lower risk of exacerbations in people treated with statins for dyslipidemia | (116, 117) |