Functional pharmacological characterization of SER100 in cardiovascular health and disease

Villar, Inmaculada Concepción; Bubb, Kristen J.; Moyes, Amie J; Steiness, Eva; Gulbrandsen, Trygve; Levy, Finn Olav; Hobbs, Adrian J.

doi:10.1111/bph.13634

Cited by 7 publications

(7 citation statements)

References 63 publications

(87 reference statements)

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“…Cut-off frequencies previously determined to be accurate for mice were used to divide the signal into three components: very low frequency (Ͻ0.4 Hz), low frequency (LF 0.4 -1.5 Hz), and high frequency (HF 1.5-4.0 Hz). Normalization to exclude very low frequency was performed, and the spectral variability at each bandwidth was normalized to the total spectral area (69).…”

Section: Methodsmentioning

confidence: 99%

Pyridostigmine regulates glucose metabolism and mitochondrial homeostasis to reduce myocardial vulnerability to injury in diabetic mice

Yang

Zhao

et al. 2019

American Journal of Physiology-Endocrinology and Metabolism

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Diabetic patients are more susceptible to myocardial ischemia damage than nondiabetic patients, with worse clinical outcomes and greater mortality. The mechanism may be related to glucose metabolism, mitochondrial homeostasis, and oxidative stress. Pyridostigmine may improve vagal activity to protect cardiac function in cardiovascular diseases. Researchers have not determined whether pyridostigmine regulates glucose metabolism and mitochondrial homeostasis to reduce myocardial vulnerability to injury in diabetic mice. In the present study, autonomic imbalance, myocardial damage, mitochondrial dysfunction, and oxidative stress were exacerbated in isoproterenol-stimulated diabetic mice, revealing the myocardial vulnerability of diabetic mice to injury compared with mice with diabetes or exposed to isoproterenol alone. Compared with normal mice, the expression of glucose transporters (GLUT)1/4 phosphofructokinase (PFK) FB3, and pyruvate kinase isoform (PKM) was decreased in diabetic mice, but increased in isoproterenol-stimulated normal mice. Following exposure to isoproterenol, the expression of (GLUT)1/4 phosphofructokinase (PFK) FB3, and PKM decreased in diabetic mice compared with normal mice. The downregulation of SIRT3/AMPK and IRS-1/Akt in isoproterenol-stimulated diabetic mice was exacerbated compared with that in diabetic mice or isoproterenol-stimulated normal mice. Pyridostigmine improved vagus activity, increased GLUT1/4, PFKFB3, and PKM expression, and ameliorated mitochondrial dysfunction and oxidative stress to reduce myocardial damage in isoproterenol-stimulated diabetic mice. Based on these results, it was found that pyridostigmine may reduce myocardial vulnerability to injury via the SIRT3/AMPK and IRS-1/Akt pathways in diabetic mice with isoproterenol-induced myocardial damage. This study may provide a potential therapeutic target for myocardial damage in diabetic patients.

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Section: Methodsmentioning

confidence: 99%

Pyridostigmine regulates glucose metabolism and mitochondrial homeostasis to reduce myocardial vulnerability to injury in diabetic mice

Yang

Zhao

et al. 2019

American Journal of Physiology-Endocrinology and Metabolism

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“…Via selective activation of the NOP receptor, N/OFQ modulates several biological functions including pain transmission, learning and memory, emotional states, locomotor activity, food intake, drug abuse, cardiovascular and gastrointestinal functions, and the cough and micturition reflexes [40]. N/OFQ and synthetic NOP receptor agonists have been shown to produce beneficial effects in different animal models of Formatted: Font: Italic pathology [41] and, currently, some of these molecules are in clinical development including cebranopadol [42] as innovative analgesic [43], SER100 (alias ZP-120 [18]) for systolic hypertension [44] [45] and REC 0438 (alias UFP-112, [46]) for urinary incontinence due to overactive bladder [47].…”

Section: Pwt-n/ofqmentioning

confidence: 99%

Peptide welding technology – A simple strategy for generating innovative ligands for G protein coupled receptors

et al. 2018

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“…Reversed-phase column chromatography (2:3, MeCN:H 2 O) afford the title compound as a white solid (0.040 g, 0.100 mmol, 26%). (36). To a solution of 30 (100 mg, 0.379 mmol) and t-Bu glycine HCl (95 mg, 0.569 mmol) in dry DMF (2 mL) at r.t. was added triethylamine (0.133 mL, 0.95 mmol), and the mixture was stirred at 80 °C for 3 h (TLC, LCMS).…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

A Series of Substituted Bis-Aminotriazines Are Activators of the Natriuretic Peptide Receptor C

et al. 2022

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C-type natriuretic peptide (CNP) is involved in the regulation of vascular homeostasis, which is at least partly mediated through agonism of natriuretic peptide receptor C (NPR-C), and loss of this signaling has been associated with vascular dysfunction. As such, NPR-C is a novel therapeutic target to treat cardiovascular diseases. A series of novel small molecules have been designed and synthesized, and their structure−activity relationships were evaluated by a surface plasmon resonance binding assay. The biological activity of hit compounds was confirmed through organ bath assays measuring vascular relaxation and inhibition of cAMP production, which was shown to be linked to its NPR-C activity. Lead compound 1 was identified as a potent agonist (EC 50 ∼ 1 μM) with promising in vivo pharmacokinetic properties.

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Functional pharmacological characterization of SER100 in cardiovascular health and disease

Cited by 7 publications

References 63 publications

Pyridostigmine regulates glucose metabolism and mitochondrial homeostasis to reduce myocardial vulnerability to injury in diabetic mice

Pyridostigmine regulates glucose metabolism and mitochondrial homeostasis to reduce myocardial vulnerability to injury in diabetic mice

Peptide welding technology – A simple strategy for generating innovative ligands for G protein coupled receptors

A Series of Substituted Bis-Aminotriazines Are Activators of the Natriuretic Peptide Receptor C

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