NDB

Research use only, not for human use.

NDB is a selective and potent hFXRα antagonist that inhibits GW4064-stimulated FXR/RXR interactions and FXRα target gene expression in primary mouse hepatocytes.NDB is used in the study of diabetes.

NDB is a selective human FXRα (hFXRα) antagonist that is effective in modulating transcription of FXRα downstream genes. NDB can be used in anti-diabetes research.

NDB induces rearrangements of helix 11 (H11) and helix 12 (H12, AF-2) by forming a homodimer of hFXRα-LBD, totally different from the active conformation in monomer state.NDB (25 μM) effectively antagonizes the GW4064-stimulated FXR/RXR interaction and FXRα target gene expression in primary mouse hepatocytes, including the small heterodimer partner (SHP) and bile-salt export pump (BSEP).

Cofrogliptin (HSK7653) (compound 2) (IV: 0.5 mg/kg; PO: 2 mg/kg) exhibits extremely long half-lives and low rate of reduction of drug concentration after orally administration.Cofrogliptin (compound 2) (Single, orally, 3 mg/kg, 10 mg/kg, 30 mg/kg) increases of half-lives, has high oral exposure, low i.v. clearance and hepatic microsomal clearance after intravenous dosing. Cofrogliptin (compound 2) (Single, orally, 10 mg/kg) exhibits longe inhibition time of DPP-4 and decreases HbA1c level at the doses of 3 and 10 mg/kg in ob/ob mice. Cofrogliptin (compound 2) (Single, orally, 10 mg/kg) also has a great potential of biweekly regimen for T2DM as indicated in rhesus monkeys.Animal Model:ob/ob mice Dosage:3 mg/kg, 10 mg/kg, 30 mg/kg Administration: Single, orally, 3 mg/kg, 10 mg/kg, 30 mg/kg Result:Exhibited strong inhibition capability of plasma DPP-4 in a dose dependent manner. Animal Model:rhesus monkeys Dosage:10 mg/kg Administration:Single, orally, 10 mg/kg Result: Possessed the capability of plasma DPP-4 inhibition over 80% for at least 12 days.Remained the plasma DPP-4 inhibition rates of 76.16% and 43.41%, respectively at the end of second week and third week after administration.

——

Metabolic Enzyme/Protease

FXR

FXR

——

——

1660153-08-1

471.42

C26H28Cl2N2O2

>98% (HPLC)

In Vitro:?DMSO : 100 mg/mL (212.13 mM; Ultrasonic )

CN(C)c1cc(Cl)c(C(=O)N(Cc2ccccc2)c2ccc(O)c(c2)C(C)(C)C)c(Cl)c1

——

(-20℃)

With Ice Pack

≥ 2 years