Novel ROCK inhibitors for the treatment of pulmonary arterial hypertension
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Heart Vessels
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A systematic review on the effects of ROCK inhibitors on proliferation and/or differentiation in human somatic stem cells: A hypothesis that ROCK inhibitors support corneal endothelial healing via acting on the limbal stem cell niche
2023, Ocular SurfaceCitation Excerpt :In 2017, netarsudil (AR-13324; Rhopressa® 0.02%), a ROCK and norepinephrine adrenergic inhibitor [37], was approved for glaucoma treatment in the US [38]. Undesirable systemic effects including hypotension [32] and lymphocytopenia [39] have somewhat curbed the broad introduction of ROCKi into clinical use, though this is less problematic in ophthalmology due to topical delivery where the most frequently reported adverse effect is transient conjunctival hyperemia [40,41]. It appears that some cellular effects of ophthalmic ROCKi may be drug-dependent, as evident from different effects on the corneal epithelium, highlighted by recent cases of reticular bullous epithelial edema associated with netarsudil [42–48] and to a lesser extent, ripasudil [49,50].
Design, synthesis and biological evaluations of a long-acting, hypoxia-activated prodrug of fasudil, a ROCK inhibitor, to reduce its systemic side-effects
2021, Journal of Controlled ReleaseCitation Excerpt :This drug is currently approved for the treatment of cerebral vasospasm in Japan and China, and reported to be efficacious in the treatment of PAH patients and animal models of PAH [12–14]. However, systemic exposure to fasudil or other Rho-kinase inhibitors induces an undesirable drop in blood pressure, reduces the lymphocyte count, and thus causes a change in the therapeutic window of the drug [8,15,16]. As such, we assume that by avoiding systemic inhibition of Rho kinase, many of the adverse effects of fasudil can be minimized to render it safe for treatment of PAH.
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2021, Comprehensive Heterocyclic Chemistry IVDevelopment of 2-(4-pyridyl)-benzimidazoles as PKN2 chemical tools to probe cancer
2020, Bioorganic and Medicinal Chemistry LettersDiscovery of thieno[2,3-d]pyrimidin-4(3H)-one derivatives as a new class of ROCK inhibitors
2020, Bioorganic and Medicinal Chemistry LettersGlucocorticoid-induced fetal origins of adult hypertension: Association with epigenetic events
2016, Vascular PharmacologyCitation Excerpt :Interestingly, dexamethasone stimulates the secretion of endothelin from rat aortic vascular smooth muscle cells, and this may contribute to glucocorticoid-induced hypertension through vasoconstriction and mitogenic processes [85]. A key player in VSMC contraction and coronary vasospasm is Rho-kinase (ROCK) [86,87]. Sustained elevation of serum cortisol is known to trigger coronary vasoconstriction through activation of ROCK [88].