A Review of the Therapeutic Potential of Recently Developed G Protein-Biased Kappa Agonists
Conclusion and Future Directions G protein bias may either be affinity/potency-dominant or efficacy-dominant (Table 1). A potential concern is that, despite using the same cellular assays, variations in agonist potency were determined by different, or even the same labs, potentially due to differences in expression levels of the receptor and signaling proteins that occurred during cell passaging. For example the reported arrestin recruitment potency for U69,593 has been reported to be as low as 67.7 nM (Spetea et al., 2017) and as high as 410 nM (Dunn et al., 2018), similarly for U50,488 potency has ranged from 36 to 1000 nM (Dunn et al., 2018; Liu et al., 2019). In our hands the values were slightly different as well, finding the following potencies and efficacies for U50,488 (EC50 = 51.5 ± 12, α = 100 ± 1), nalfurafine (EC50 (nM) = 5.19 ± 1.3, α = 84 ± 7), and salvinorin A (EC50 = 27.5 ± 10, α = 76 ± 9), whilst also confirming super recruitment by GR89,696 (EC50 = 9.90 ± 3.6, α = 112 ± 3), but partial recruitment of dynorphin A (EC50 = 21.0 ± 13, α = 87 ± 5) relative to U50,488 (Figure 3). These potency differences as well as which reference compound is used will impact the calculated bias factor, which is the reason why we did not include bias factors in Table 1. It would be helpful for the field if the endogenous agonist dynorphin A was used as reference compound to ensure...
Publication date: Available online 23 September 2020Source: Anaesthesia Critical Care &Pain MedicineAuthor(s): Vincent Laudenbach, Aude Charollais, Sophie Radi, Marie-Hélène Stumpf, Anne Vincent, Ingrid Kaltwasser, Tiphaine Tomczyk, Jacques Benichou, Philippe Leroux, Stéphane Marret
The president ’s promises on health care stand in stark contrast with his legislative, regulatory and legal record.
Conclusion: IL-23 inhibitors are safe and efficacious therapeutic options for patients with psoriasis and should be considered as a potential first-line therapy alone or in combination with topical medications, phototherapy, and other systemic non-biologic agents. Consideration should be given to the evidence-based guidelines of global dermatologic organizations to help guide therapeutic decisions. PMID: 32962478 [PubMed - as supplied by publisher]
Authors: Marques E, Paluch Z, Boháč P, Slanař O, Běláček J, Hercogová J Abstract INTRODUCTION: Understanding how different comorbidities and epidemiological factors are related to psoriasis severity can help us estimating patients' clinical outcome. AIM: Establish possible prognostic factors of severe psoriasis. METHODS: Three groups of patients were included: 118 were on topical therapy, 83 used conventional systemic drugs and 112 were treated with biological agents. Based of the fact that patients on topical therapy have a lower grade of disease severity than patients treated syst...
Authors: Lam PH, Hon KL, Leung K, Leong KF, Li CK, Leung TF Abstract BACKGROUND: Atopic eczema (AE) is a common relapsing inflammatory skin disease in children which is often associated with chronicity and poor quality of life. Unlike atopic asthma, control of AE is seldom assessed in therapeutics. AIM: To investigate the utility of a Traffic Light Control (TLC) system as a measurement/assessment of self-perceived eczema control. METHODS: This is a prospectively study of all Chinese children (aged 6 to 18 years old) with eczema attending the paediatric dermatology clinic of a tertiary hospital from Jan to J...
Publication date: Available online 23 September 2020Source: Progress in Neuro-Psychopharmacology and Biological PsychiatryAuthor(s): Igor Łoniewski, Agata Misera, Karolina Skonieczna-Żydecka, Mariusz Kaczmarczyk, Karolina Kaźmierczak-Siedlecka, Błażej Misiak, Wojciech Marlicz, Jerzy Samochowiec
This initiative aims to support the development and testing of systems-level interventions targeting high-risk youth to reduce or prevent suicide and suicidal behavior in these populations. Populations identified with high suicide risk and high unmet service need include but are not limited to: youth in public service systems, racial/ethnic minority youth, sexual and gender minority (SGM) youth, rural youth, and youth with intersectional risk. Relevant settings include but are not limited to: education or training programs, housing programs, juvenile justice, and child welfare.
The primary objective of this Funding Opportunity Announcement (FOA) is to advance translational research to better understand risk and resilience for suicide in the context of the Research Domain Criteria (RDoC) framework and the Positive Valence Systems (PVS) domain.
This FOA seeks to encourage research addressing major gaps identified in the United States Preventive Services Task Force (USPSTF) recommendation statement concerning interventions to prevent perinatal depression.
Publication date: Available online 23 September 2020Source: Molecular and Cellular NeuroscienceAuthor(s): Virginie Rappeneau, Lars Wilmes, Chadi Touma
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