کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8344503 | 1541582 | 2018 | 30 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Discovery and development of next generation sGC stimulators with diverse multidimensional pharmacology and broad therapeutic potential
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کلمات کلیدی
inflammation - التهاب( توروم) Stimulator - تحریک کنندهDrug development - توسعه داروییVascular function - عملکرد عروقیSmooth muscle function - عملکرد عضلانی صافNeuronal function - عملکرد نورونFibrosis - فیبروز یا فساد الیافMetabolism - متابولیسم Nitric oxide - نیتریک اکسیدguanylyl cyclase - گویینیل سیکلاس
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Nitric oxide (NO)-sensitive soluble guanylyl cyclase (sGC), an enzyme that catalyzes the conversion of guanosine-5â²-triphosphate (GTP) to cyclic guanosine-3â²,5â²-monophophate (cGMP), transduces many of the physiological effects of the gasotransmitter NO. Upon binding of NO to the prosthetic heme group of sGC, a conformational change occurs, resulting in enzymatic activation and increased production of cGMP. cGMP modulates several downstream cellular and physiological responses, including but not limited to vasodilation. Impairment of this signaling system and altered NO-cGMP homeostasis have been implicated in cardiovascular, pulmonary, renal, gastrointestinal, central nervous system, and hepatic pathologies. sGC stimulators, small molecule drugs that synergistically increase sGC enzyme activity with NO, have shown great potential to treat a variety of diseases via modulation of NO-sGC-cGMP signaling. Here, we give an overview of novel, orally available sGC stimulators that Ironwood Pharmaceuticals is developing. We outline the non-clinical and clinical studies, highlighting pharmacological and pharmacokinetic (PK) profiles, including pharmacodynamic (PD) effects, and efficacy in a variety of disease models.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Nitric Oxide - Volume 78, 1 August 2018, Pages 72-80
Journal: Nitric Oxide - Volume 78, 1 August 2018, Pages 72-80
نویسندگان
E.S. Buys, D.P. Zimmer, J. Chickering, R. Graul, Y.T. Chien, A. Profy, J.R. Hadcock, J.L. Masferrer, G.T. Milne,