Enoxacin (AT 2266) is a fluoroquinolone antibiotic, which disrupts bacterial DNA by inhibiting DNA gyrase and topoisomerase IV, with IC50 values of 126 µg/ml and 26.5 µg/ml, respectively. It also functions as a miRNA processing activator, enhancing siRNA-mediated mRNA degradation and promoting the biogenesis of endogenous miRNAs. Enoxacin exhibits potent antibacterial activity against both gram-positive and gram-negative bacteria and acts as a cancer-specific growth inhibitor by boosting TAR RNA-binding protein 2 (TRBP)-mediated microRNA processing[1].[2].[3].[4].
体内研究
Furthermore, in an in vivo study, in GFP transgenic mice, Enoxacin administered at 100 µM in a volume of 2 µl directly into the ear once a day for three consecutive days (days 12, 13, and 14), significantly enhances GFP mRNA knockdown efficiency mediated by Lv-siGFP (from 80% to 60%; leaving 40% GFP mRNA levels), while having no effect on GFP expression when administered alone in the GFP transgenic line C57BL/6-Tg(ACTB-EGFP)1Osb/J (aged 10 days) with lentivirus expressing shGFP (Lv-siGFP; injected into the ear for 10 days)[3].
体外研究
In cell-based assays, Enoxacin increases siGFP-mediated gene knockdown in a dose-dependent manner within a HEK293 cells-based reporter system, showing an effective concentration (EC50) of about 30 µM. It specifically enhances the processing of miRNAs and the loading of siRNA duplexes onto RISCs in these cells at a concentration of 50 µM[3].
Enoxacin does not affect the processing of pre-let-7 or pre-miR-30a by Dicer alone, but when combined with TRBP, it enhances their processing by Dicer[3].
Enoxacin is effective against various bacterial strains, inhibiting 90% of pathogens like Escherichia coli, Klebsiella sp., Aeromonas sp., Enterobacter spp., Serratia spp., Proteus mirabilis, and Morganella morganii at concentrations less than or equal to 0.8 micrograms/ml[5].
Enoxacin/依诺沙星 细胞实验
Cell Line
Concentration
Treated Time
Description
References
HeLa cells
50 µM
48 hours
Enhances siRNA-mediated gene silencing
Nat Biotechnol. 2008 Aug;26(8):933-40.
NIH3T3 cells
50 µM
48 hours
Enhances siRNA-mediated gene silencing
Nat Biotechnol. 2008 Aug;26(8):933-40.
HEK293 cells
50 µM
48 hours
Enhances siRNA-mediated mRNA degradation and promotes the biogenesis of endogenous miRNAs
Nat Biotechnol. 2008 Aug;26(8):933-40.
C2C12 myotubes
100 µM
During differentiation for 4 days
Enoxacin upregulated Ppargc1a and multiple PPAR target genes related to oxidative metabolism, increasing maximal mitochondrial respiration, proton leak, and spare capacity.
Sci Adv. 2020 Dec 2;6(49):eabc6250.
Human adipose-derived stem cells (hASC)
50 µM
10 days post-differentiation
Enoxacin treatment increased UCP1 and PPARGC1A mRNA levels by 1.9- and 2.5-fold, respectively, with no changes in FABP4 expression.
Sci Adv. 2020 Dec 2;6(49):eabc6250.
Mouse subcutaneous preadipocytes (9W)
50 µM
During differentiation (days 2 to 8) or for 24 hours post-differentiation
Enoxacin enhanced amiRNA-mediated sgRNA repression by promoting the loading of amiRNAs onto miRISCs, thereby inhibiting the function of the CRISPR-Cas9 system
Theranostics. 2020 May 17;10(15):6661-6673.
NSC-34 cells
100 μM
72 hours
To test whether enoxacin could reverse the negative effect of ALS-causing mutant proteins on miRNA processing. Results showed that enoxacin partially ameliorated the impairments in pre-miRNA processing caused by FUS R495X, TDP-43 A315T, or SOD1 G93A mutations.
Iron chelators enhance shRNA-EGFP-mediated gene silencing.
Cell Metab. 2012 Jun 6;15(6):895-904.
Normal fibroblast cells (Wi-38 and MRC-5)
40 μg/mL
5 days
To evaluate the effect of enoxacin on normal cells, results showed that enoxacin had no significant effect on the growth of normal fibroblast cells
Proc Natl Acad Sci U S A. 2011 Mar 15;108(11):4394-9.
Colorectal cancer cells (HCT-116)
40 μg/mL
5 days
To evaluate the effect of enoxacin on cancer cell growth, results showed that enoxacin significantly inhibited the growth of HCT-116 cells
Proc Natl Acad Sci U S A. 2011 Mar 15;108(11):4394-9.
MC3T3-E1 cells
1, 10, 50, 100 μM
Enoxacin at concentrations up to 50 μM had no effect on the growth and alkaline phosphatase activity of MC3T3-E1 cells, while 100 μM caused reduced growth and morphological changes
J Med Chem. 2009 Aug 27;52(16):5144-51.
Mouse marrow cells
1, 10, 100 μM
7 days
Enoxacin dose-dependently reduced the number of TRAP+ cells, inhibiting osteoclast differentiation
J Med Chem. 2009 Aug 27;52(16):5144-51.
Enoxacin/依诺沙星 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
GFP transgenic mice
Ear injection
100 µM
Once daily for 3 consecutive days
Enhances siRNA-mediated mRNA degradation
Nat Biotechnol. 2008 Aug;26(8):933-40.
C57BL/6 mice
High-fat diet-induced obesity model
Intraperitoneal injection
10 mg/kg body weight/day
5 intraperitoneal injections/week for 10 weeks
Enoxacin mitigated high-fat diet-induced obesity, increased energy expenditure, improved glucose tolerance and insulin sensitivity, with no effects on food intake or gut microbiota composition.
Sci Adv. 2020 Dec 2;6(49):eabc6250.
Mice
SOD1 G93A ALS mouse model
Oral
800 mg/kg body weight/day
Once daily, starting from day 42
To evaluate the effect of enoxacin on neuromuscular function in ALS mice. Results showed that enoxacin treatment delayed the onset of neurological symptoms and improved neuromuscular function, but did not significantly extend lifespan.
Xenograft model of colorectal cancer cells (HCT-116 and RKO)
Intraperitoneal injection
10 mg/kg
Once daily for 4 weeks
To evaluate the inhibitory effect of enoxacin on tumor growth in vivo, results showed that enoxacin significantly inhibited the tumor growth of HCT-116 and RKO cells
Proc Natl Acad Sci U S A. 2011 Mar 15;108(11):4394-9.
Mice
Marrow culture model
Culture medium addition
10, 25, 100 μM
5 days
Enoxacin dose-dependently reduced bone resorption area and pit numbers, with complete inhibition at 100 μM
J Med Chem. 2009 Aug 27;52(16):5144-51.
Gnotobiotic mice
ZIKV infection model
Intraperitoneal injection
10 mg/kg
Daily from E1.5 to E18.5
To evaluate the effect of enoxacin on ZIKV-associated fetal growth restriction and placental viral persistence, showing that enoxacin treatment abolished placental ZIKV persistence and rescued fetal growth restriction
United States, Kentucky
... 展开 >>
University of Louisville
Recruiting
Louisville, Kentucky, United States, 40202
Contact: Julio A Ramirez, MD 502-852-1148 jarami01@louisville.edu
Contact: David Seligson, MD 502-852-0923 d0seli01@louisville.edu
Sub-Investigator: Forest Arnold, DO
Sub-Investigator: Timothy Wiemkwn, PhD
Sub-Investigator: Robert Kelley, PhD
Sub-Investigator: James Summersgill, PhD
Sub-Investigator: Ruth Carrico, PhD
Sub-Investigator: Julie Harting, PharmD
Sub-Investigator: Paula Peyrani, MD
Principal Investigator: David Seligson, MD
Sub-Investigator: Craig Roberts, MD
Principal Investigator: Julio Ramirez, MD 收起 <<
CI 919; AT 2266; Sesquihydrate, Enoxacin; Brand of Enoxacin Sesquihydrate; Pierre Fabre Brand of Enoxacin; Enoxacino; Comprecin; Enoxacine; Penetrex; NSC 629661; Pd107779
运输
蓝冰
存储条件
In solvent-20°C:3-6个月-80°C:12个月
Pure formKeep in dark place, sealed in dry, room temperature
United States, Kentucky
... 展开 >>
University of Louisville
Recruiting
Louisville, Kentucky, United States, 40202
Contact: Julio A Ramirez, MD 502-852-1148 jarami01@louisville.edu
Contact: David Seligson, MD 502-852-0923 d0seli01@louisville.edu
Sub-Investigator: Forest Arnold, DO
Sub-Investigator: Timothy Wiemkwn, PhD
Sub-Investigator: Robert Kelley, PhD
Sub-Investigator: James Summersgill, PhD
Sub-Investigator: Ruth Carrico, PhD
Sub-Investigator: Julie Harting, PharmD
Sub-Investigator: Paula Peyrani, MD
Principal Investigator: David Seligson, MD
Sub-Investigator: Craig Roberts, MD
Principal Investigator: Julio Ramirez, MD 收起 <<
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