000 02550 am a22002533u 4500
042 _adc
100 1 0 _aLeber, Andrew
_eauthor
_9694
700 1 0 _aHontecillas, Raquel
_eauthor
_9695
700 1 0 _aZoccoli-Rodriguez, Victoria
_eauthor
_9696
700 1 0 _aEhrich, Marion
_eauthor
_9697
700 1 0 _aChauhan, Jyoti
_eauthor
_9698
700 1 0 _aBassaganya-Riera, Josep
_eauthor
_9699
245 0 0 _aExploratory Studies with NX-13: Oral toxicity and pharmacokinetics in rodents of an orally active, gut-restricted first-in-class therapeutic for IBD that targets NLRX1
260 _c2022-01.
500 _a/pmc/articles/PMC7182494/
500 _a/pubmed/31650868
520 _aNucleotide-binding oligomerization domain, leucine rich repeat containing X1 (NLRX1) is an emerging therapeutic target for a spectrum of human diseases. NX-13 is a small molecule therapeutic designed to target and activate NLRX1 to induce immunometabolic changes resulting in lower inflammation and therapeutic responses in inflammatory bowel disease (IBD). This study investigates the safety of NX-13 in a seven-day, repeat-dose general toxicity study in male and female Sprague Dawley rats at oral doses of 500 and 1000 mg/kg. Weights, clinical signs, functional observational battery, clinical pathology and histopathology were used for evaluation. Daily oral dosing of NX-13 up to 1000 mg/kg did not result in any changes in weight, abnormal clinical signs or behavior. No significant differences were observed between treated and control rats in hematology or blood biochemistry. Histopathological evaluation of 12 tissues demonstrated no differences between controls and treated rats. There were no changes in weights of brain, heart, kidney, liver or spleen. Pharmacokinetic analysis of a single oral dose of NX-13 at 10 mg/kg in Sprague Dawley rats provided a maximum plasma concentration of 57 ng/mL at 0.5 h post-dose. Analysis of colon tissue after oral dosing with 1 and 10 mg/kg indicated high peak concentrations (10 and 100 μg/g, respectively) that scale in a dose-proportional manner. These experiments suggest that NX-13 is safe and well-tolerated in rats given oral doses as high as 1000 mg/kg with a favorable gastrointestinal localized pharmacokinetic profile, confirming NX-13 as a promising therapeutic for Crohn's disease and ulcerative colitis.
540 _a
546 _aen
690 _aArticle
655 7 _aText
_2local
786 0 _nDrug Chem Toxicol
856 4 1 _uhttp://dx.doi.org/10.1080/01480545.2019.1679828
_zConnect to this object online.
999 _c1433
_d1433