Publications by authors named "Fritz Kramer"
The murine tumor cell line LA-4 (also known as LA4 or LA 4) has been extensively used in ~70 studies from 1975 to present. However, the genetic characteristics have not been comprehensively delineated, apart from a single solid-stain cytogenetic study, which reported an average of 116 chromosomes per cell. LA-4 was created via urethane induction in an A/He mouse and demonstrated characteristic features of lung adenoma cells.
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- A new class of H-PGDS inhibitors, specifically 2-phenylimidazo[1,2-a]pyridine-6-carboxamide, was discovered through a virtual screening process at GlaxoSmithKline.
- Detailed analysis of crystal structures and structure-activity relationships (SAR) resulted in the identification of a powerful, orally active imidazopyridine inhibitor, designated as 20b.
- The text discusses the identification of two types of inhibitors, their synthesis processes, and the challenges encountered during the research.
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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.
View Article and Find Full Text PDFWith the goal of discovering more selective anti-inflammatory drugs, than COX inhibitors, to attenuate prostaglandin signaling, a fragment-based screen of hematopoietic prostaglandin D synthase was performed. The 76 crystallographic hits were sorted into similar groups, with the 3-cyano-quinoline 1a (FP IC = 220,000 nM, LE = 0.43) being a potent member of the 6,6-fused heterocyclic cluster.
View Article and Find Full Text PDFBiomarkers of muscle protein synthesis rate could provide early data demonstrating anabolic efficacy for treating muscle-wasting conditions. Androgenic therapies have been shown to increase muscle mass primarily by increasing the rate of muscle protein synthesis. We hypothesized that the synthesis rate of large numbers of individual muscle proteins could serve as early response biomarkers and potentially treatment-specific signaling for predicting the effect of anabolic treatments on muscle mass.
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