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  3. FHND5032

FHND5032 is an orally active miR-124 inducer. FHND5032 significantly upregulates miR-124 expression in macrophages. FHND5032 disrupts inflammatory signaling, promotes macrophage reprogramming, and restores the epithelial barrier function by inhibiting the PIK3R2/PI3K/Akt axis. FHND5032 alleviates colitis and reduces inflammatory burden in ulcerative colitis mice. FHND5032 can be used for the study of ulcerative colitis.

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FHND5032 Chemical Structure

FHND5032 Chemical Structure

CAS No. : 3076057-63-8

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Description

FHND5032 is an orally active miR-124 inducer. FHND5032 significantly upregulates miR-124 expression in macrophages. FHND5032 disrupts inflammatory signaling, promotes macrophage reprogramming, and restores the epithelial barrier function by inhibiting the PIK3R2/PI3K/Akt axis. FHND5032 alleviates colitis and reduces inflammatory burden in ulcerative colitis mice. FHND5032 can be used for the study of ulcerative colitis[1].

In Vitro

FHND5032 (0-20 μM, 24 h) significantly exerts anti-inflammatory activity in THP-1 and RAW 264.7 cells by enhancing miR-124 expression[1].
FHND5032 (≤ 5 μM) activates miR-124-5p expression to regulate the PI3K/Akt pathway by targeting PIK3R2 in THP-1 and RAW 264.7 cells reprogramming[1].
FHND5032 decreases the expression of M1 marker CD86 while increasing the expression of M2 marker CD206 in RAW 264.7 cells[1].
FHND5032 promots the expression of the barrier-sealing proteins ZO-1 and occludin to facilitate Tight junction (TJ) assembly in Caco-2 cells[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Real Time qPCR[1]

Cell Line: THP-1 and RAW 264.7 cells
Concentration: 5, 10 μM
Incubation Time: /
Result: Upregulated miR-124 levels and induced miR-124 expression, which peaked at a concentration of 5 μM.
Decreased TNF-α, IL-1β, and IL-6 expression in LPS (HY-D1056)- and IFN-γ-stimulated THP-1 cells and LPS stimulated RAW 264.7 cells.
Decreased the expression of PIK3R2
In Vivo

FHND5032 (25-50 mg/kg, i.g., daily, 12 days) alleviates colitis and reduces inflammatory burden in Dextran sulfate sodium salt (DSS) (HY-116282C)-induced ulcerative colitis (UC) mice[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: DSS-induced female C57BL/6J mice (18-20 g)[1]
Dosage: 25, 50 mg/kg
Administration: i.g. daily for 12 days
Result: Restrained the body weight loss of DSS-induced colitis mice.
Reduced the hematochezia occurrence during treatment.
Showed longer colon length of mice.
Protected the colonic barrier from pathological damage.
Decreased the local level of UC-associated myeloperoxidase (MPO) in the colon.
Reduced the expression of pro-inflammatory cytokines, including IL-6, TNF-α, and IFN-γ.
Increased the expression of anti-inflammatory cytokines IL-10.
Prevented intestinal damage in UC through elevation of TJ proteins.
Prevented the FITC-dextran leakage.
Inhibited colonic inflammation and repaired the intestinal barrier in colitis mice.
Upregulated the miR-124 expression and decreased PIK3R2 expression.
Attenuated PIK3R2 upregulation and the hyperphosphorylation of PI3K and Akt.
Showed no significant discrepancies in serum physicochemical parameters (alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine (Cr)).
Decreased the abundance of Proteobacteria in colitis mice and effectively enhanced the relative abundance of Firmicutes.
Showed no increase on the abundance of Bacteroidota.
Molecular Weight

339.70

Formula

C15H9ClF3N3O

CAS No.
SMILES

FC(F)(OC1=CC=C(C=C1)NC2=NC3=CC(Cl)=CC=C3C=N2)F

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    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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FHND5032
Cat. No.:
HY-174976
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