RTC13 / UCLA - LARVOL DELTA

Discovery of a 2'-α-Fluoro-2'-β-C-(fluoromethyl) Purine Nucleotide Prodrug as a Potential Oral Anti-SARS-CoV-2 Agent. (PubMed, J Med Chem) - "The cryo-electron microscopy structure of the C-RTC:13-TP complex was also determined...Furthermore, it was well tolerated in rats at doses of up to 2000 mg/kg, and a single oral dose of this prodrug at 40 mg/kg led to high levels of 13-TP in the target organ lungs of rats with a long half-life. These findings support the further development of compound 15 as an orally available antiviral agent for the treatment of SARS-CoV-2 infection."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Generation of the First Human In Vitro Model for McArdle Disease Based on iPSC Technology. (PubMed, Int J Mol Sci) - "As a proof-of-concept, we have tested in this model the rescue of PYGM expression by two different read-through compounds (PTC124 and RTC13). The developed model will be very useful as a platform for testing drugs or compounds with potential pharmacological activity."

Journal • Preclinical

Absence of p.R50X Pygm read-through in McArdle disease cellular models. (PubMed, Dis Model Mech) - "We used three different cellular models to evaluate the efficiency of different read-through agents (including amlexanox, Ataluren, RTC13 and G418) in McArdle disease. Besides, we performed a literature search and compared the premature termination codon context sequences with reported positive and negative read-through induction and identified a potential role for nucleotide positions -9, -8, -3, -2, +13 and +14 (first nucleotide of the stop codon is assigned as +1). The Pygm p.R50X mutation presents TGA as a stop codon, G nucleotide at positions -1 and -9 and a C at -3, which potentially generate a good context for read-through induction, counteracted by the presence of a C at -2 and its absence at +4."

Journal • Metabolic Disorders • Myositis

Variable readthrough responsiveness of nonsense mutations in hemophilia A. (PubMed, Haematologica) - "The aim of this study was to measure the readthrough effect of different compounds and to analyze the influence of premature termination codon context in selected nonsense mutations causing hemophilia A. To this end, primary fibroblasts from three patients with hemophilia A caused by nonsense mutations (p.W1586X, p.Q1636X and p.R1960X) and CHO cells transfected with 12 different plasmids encoding mutated F8 (p.Q462X, p.Q1705X, p.Q1764X, p.W274X, p.W1726X, p.W2015X, p.W2131X, p.R1715X, p.R1822X, p.R1960X, p.R2071X and p.R2228X) were treated with gentamicin, geneticin, PTC124, RTC13 or RTC14. In CHO cells, only in five of the twelve F8 variants, readthrough treatment increased both FVIII antigen and activity levels, which was associated with a reduction of intracellular accumulation of truncated forms and an increase of full-length proteins. These results provide experimental evidence of genetic context dependence of nonsense suppression by readthrough agents and of..."

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