| 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 |
_c1314 _d1314 |
||