DprE1-IN-1 是一种有效且有口服活性的DprE1抑制剂，具有良好的肝细胞稳定性、低细胞毒性和低HERG通道抑制。DprE1-IN-1对DprE1-IN-1对药敏和临床分离的耐药结核菌株均有有效抗性 (MICs<0.1 μg/mL)，以及在巨噬细胞内抗分支杆菌活性良好，能减少1.29 log10CFU。

DprE1-IN-1 is a potent, orally active DprE1 inhibitor with favorable hepatocyte stability, low cytotoxicity and low hERG channel inhibition. DprE1-IN-1 displays potent activity against both drug-susceptible and clinically isolated drug-resistant Tuberculosis strains with MIC s<0.1 μg/mL, as well as good intracellular antimycobacterial activity with a 1.29 log 10 CFU reduction in macrophages [1].

DprE1-IN-1 (compound 17b) (64 to 0.26 μg/mL; 48 hours) has high safety with low cytotoxicity towards HepG2, J774A.1 macrophage cells (IC 50 >60 μg/mL) and Vero (IC 50 =58.18 μg/mL) alongside potent efficacy and good druggability [1]. DprE1-IN-1 can reduce 1.19 and 1.29 log 10 CFU M. tuberculosis in J774A.1 macrophages at 5 μg/mL and 10 μg/mL, respectively, for 3 days treatment [1]. DprE1-IN-1 (compound 17b) (1 μM; 0-120 minutes) has high stability in human and mice hepatocytes (remaining of 42% and 49.7%, respectively; t 1/2 of 24.0 and 29.7 min, respectively) [1]. Cell Cytotoxicity Assay Cell Line: Vero, HepG2 and mouse J774A.1 macrophage cells [1] Concentration: 64 to 0.26 μg/mL Incubation Time: 48 hours Result: Displayed high safety with low cytotoxicity towards HepG2, J774A.1 macrophage cells (IC 50 >60 μg/mL) and Vero (IC 50 =58.18 μg/mL) alongside potent efficacy and good druggability.

DprE1-IN-1 (100 mg/kg; oral gavage; 5 days per week from day 10 until day 30) can reduce the bacterial burden in the lungs by 0.54 log 10 CFU after three weeks of treatment in M. tuberculosis H37Rv infected mice [1]. Animal Model: Female SPF Balb/c mice (18-20 g) ( M. tuberculosis H37Rv infected) [1] Dosage: 100 mg/kg Administration: Oral gavage; 5 days per week from day 10 until day 30 Result: Reduced the bacterial burden in the lungs by 0.54 log 10 CFU compared with the untreated control group after three weeks of treatment.

920459-41-2

C19H21N3O6S2

451.52

(< 1 mg/ml refers to the product slightly soluble or insoluble )
Powder: -20°C for 3 years
In solvent: -80°C for 2 years