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Evaluation of Systemic and Brain Pharmacokinetic Parameters for Repurposing Metformin Using Intravenous Bolus Administration [Drug Discovery and Translational Medicine]

ASPET

Yet, the absence of established systemic and brain pharmacokinetic (PK) parameters at relevant pre-clinical doses presents a significant knowledge gap. Our findings emphasize the importance of metformin dose selection based on pharmacokinetic parameters for pre-clinical pharmacological studies.

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Biodistribution of Agmatine to Brain and Spinal Cord Following Systemic Delivery [Neuropharmacology]

ASPET

These protocols were then used to determine the plasma pharmacokinetics of agmatine and the extent of distribution to the CNS. Upon application of this protocol to pharmacokinetic study, IV agmatine showed a half-life in plasma ranging between 18.9 The protocol also adequately withstood stability and dilution conditions.

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Benzimidazole–Oxadiazole Hybrids—Development in Medicinal Chemistry: An Overview

Chemical Biology and Drug Design

The present work systematically gives a comprehensive review in current developments of benzimidazole–oxadiazole hybrid compounds in the whole range of medicinal chemistry and the perspectives that they hold for future research. Benzimidazole and oxadiazole cores can either be fused or incorporated using either functional groups/bonds.

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Nonclinical Profile of PF-06952229 (MDV6058), a Novel TGF{beta}RI/Activin Like Kinase 5 (ALK-5) Inhibitor Supports Clinical Evaluation in Cancer [Drug Discovery and Translational Medicine]

ASPET

PF-06952229 (MDV6058) selected using rational drug design is a potent and selective TGFβRI inhibitor (TGFβRIi) with a relatively clean off-target selectivity profile and good pharmacokinetic properties across species. The compound presents an acceptable ICHS9 compliant profile for the intended-to-treat cancer patients.

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Clinical Development of the GluN2B-selective NMDA Receptor Inhibitor NP10679 for the Treatment of Neurologic Deficit after Subarachnoid Hemorrhage [Neuropharmacology]

ASPET

The delayed nature of cerebral ischemia secondary to SAH-related vasculopathy presents a window of opportunity for the evaluation of well-tolerated neuroprotective agents administered soon after ictus. Neither nimodipine nor NP10679 alter each other's pharmacokinetic profile, suggesting no obvious drug-drug interactions.

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Evaluating the Abuse Potential of Lenabasum, a Selective CB2 Cannabinoid Receptor Agonist [Behavioral Pharmacology]

ASPET

Background: Endocannabinoids, which are present throughout the central nervous system (CNS), can activate CB1 and CB2 receptors. Secondary VAS and pharmacokinetic (PK) endpoints and adverse events were assessed. CB1 and CB2 agonists exhibit broad anti-inflammatory properties, suggesting their potential to treat inflammatory diseases.

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The Novel GlycoPEGylated FGF21 Analog Pegozafermin Activates Human FGF Receptors and Improves Metabolic and Liver Outcomes in Diabetic Monkeys and Healthy Human Volunteers [Drug Discovery and Translational Medicine]

ASPET

Pharmacokinetic half-lives ranged from 55 to 100 hours over the clinically relevant dose range, consistent with the expected half-life extension by glycoPEGylation. These findings provide evidence that pegozafermin is a promising candidate molecule for the treatment of patients with NASH or SHTG.