Publications by authors named "Alan McDougal"
An unmet medical need remains for patients suffering from dry eye disease (DED). A fast-acting, better-tolerated noncorticosteroid anti-inflammatory eye drop could improve patient outcomes and quality of life. Herein, we describe a small-molecule drug discovery effort to identify novel, potent, and water-soluble JAK inhibitors as immunomodulating agents for topical ocular disposition.
View Article and Find Full Text PDFA new class of ocular steroids designed to mitigate steroid-induced intraocular pressure (IOP) elevation while maintaining anti-inflammatory activity was developed. Herein is described the discovery and preclinical characterization of ROCK'Ster compound . Codrugs consisting of a Rho kinase inhibitor (ROCKi) and a corticosteroid were synthesized.
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- Duchenne muscular dystrophy (DMD) is a muscle-wasting condition caused by dystrophin loss, with current treatments insufficient for muscle damage during eccentric contractions.
- A study using MDX mice indicated that exercise-induced muscle injury significantly reduces nicotinamide adenine dinucleotide (NAD) levels, vital for muscle health; strategies tested to enhance NAD levels included a precursor and a CD38 inhibitor.
- While inhibiting CD38 showed more potential than supplementing with the precursor, neither method resulted in sustained increases in NAD levels, muscle damage reduction, or improved strength after muscle stress.
Article Synopsis
- GlaxoSmithKline and Astex Pharmaceuticals identified GSK2894631A as a strong H-PGDS inhibitor but faced CNS toxicity with prolonged high doses.
- To reduce brain penetration, they developed aza-quinolines, modifying nitrogen positions to improve enzyme compatibility.
- The research culminated in discovering 1,8-naphthyridine, a potent and safer H-PGDS inhibitor effective in various inflammatory models without CNS side effects.
MG53 is a muscle-specific TRIM-family protein that presides over the cell membrane repair response. Here, we show that MG53 present in blood circulation acts as a myokine to facilitate tissue injury-repair and regeneration. Transgenic mice with sustained elevation of MG53 in the bloodstream (tPA-MG53) have a healthier and longer life-span when compared with littermate wild type mice.
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- The authors of the original article identified a mistake regarding the data and materials availability section.
- This discrepancy was noted on page 12 of the article.
- The authors are bringing attention to this issue after the article's publication.
Article Synopsis
- The study investigates how prolyl hydroxylase inhibitors, which stabilize hypoxia-inducible factors (HIFs), can enhance skeletal muscle repair after injury in both mice and humans, potentially countering issues like fibrosis and fatty tissue buildup.* -
- In mouse experiments, the inhibitor GSK1120360A significantly improved muscle recovery post-injury, working through myeloid HIF1α and iNOS activity rather than EPO modulation.* -
- Tests in healthy human volunteers showed that the inhibitor daprodustat reduced muscle damage markers after exercise, but did not improve functional recovery, indicating some similarities and differences in response between species.*
Article Synopsis
- Satellite cells are specialized stem cells in adult muscles that help generate new muscle tissue after injury, but their regenerative ability decreases with age.
- Research found that certain compounds, specifically 2,4-diaminopyrimidines, can boost the proliferation of these satellite cells and enhance muscle repair in mouse models.
- The study aims to identify the molecular targets responsible for this increased proliferation, paving the way for developing new therapies for muscle repair and regeneration.