We have located links that may give you full text access.
PK/PD Modeling of the PDE7 Inhibitor-GRMS-55 in a Mouse Model of Autoimmune Hepatitis.
Pharmaceutics 2021 April 22
This study aimed to assess the efficacy and explore the mechanisms of action of a potent phosphodiesterase (PDE)7A and a moderate PDE4B inhibitor GRMS-55 in a mouse model of autoimmune hepatitis (AIH). The concentrations of GRMS-55 and relevant biomarkers were measured in the serum of BALB/c mice with concanavalin A (ConA)-induced hepatitis administered with GRMS-55 at two dose levels. A semi-mechanistic PK/PD/disease progression model describing the time courses of measured biomarkers was developed. The emetogenicity as a potential side effect of the studied compound was evaluated in the α2 -adrenoceptor agonist-induced anesthesia model. The results indicate that liver damage observed in mice challenged with ConA was mainly mediated by TNF-α and IFN-γ. GRMS-55 decreased the levels of pro-inflammatory mediators and the transaminase activities in the serum of mice with AIH. The anti-inflammatory properties of GRMS-55, resulting mainly from PDE7A inhibition, led to a high hepatoprotective activity in mice with AIH, which was mediated by an inhibition of pro-inflammatory signaling. GRMS-55 did not induce the emetic-like behavior. The developed PK/PD/disease progression model may be used in future studies to assess the potency and explore the mechanisms of action of new investigational compounds for the treatment of AIH.
Full text links
Related Resources
Trending Papers
Consensus Statement on Vitamin D Status Assessment and Supplementation: Whys, Whens, and Hows.Endocrine Reviews 2024 April 28
The Tricuspid Valve: A Review of Pathology, Imaging, and Current Treatment Options: A Scientific Statement From the American Heart Association.Circulation 2024 April 26
Intravenous infusion of dexmedetomidine during the surgery to prevent postoperative delirium and postoperative cognitive dysfunction undergoing non-cardiac surgery: a meta-analysis of randomized controlled trials.European Journal of Medical Research 2024 April 19
Interstitial Lung Disease: A Review.JAMA 2024 April 23
Management of Diverticulitis: A Review.JAMA Surgery 2024 April 18
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app