| Protocol | In Vitro | In vitro activity: DprE1-IN-1, a 1,4-azaindole analog, is a potent inhibitor of decaprenylphosphoryl-β-d-ribose-2'-epimerase (DprE1) with ic50 of 10 nM; it also inhibits PDE6 with IC50 of 6 uM. It demonstrats efficacy in a rodent model of tuberculosis, making it promising for further development. DprE1-IN-1 has excellent in vitro and in vivo antimycobacterial potency through noncovalent inhibition of decaprenylphosphoryl-β-d-ribose-2'-epimerase (DprE1). Nevertheless, high mouse metabolic turnover and phosphodiesterase 6 (PDE6) off-target activity limited its advancement. In summary, DprE1-IN-1 is a promising candidate for the development of a novel anti-TB drug. Kinase Assay: DprE1-IN-1, a 1,4-azaindole analog, is a potent inhibitor of decaprenylphosphoryl-β-d-ribose-2'-epimerase (DprE1) with ic50 of 10 nM; it also inhibits PDE6 with IC50 of 6 uM. |
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| In Vivo | DprE1-IN-1 demonstrats efficacy in a rodent model of tuberculosis, making it promising for further development. The pharmacokinetic profile of DprE1-IN-1 as a representative of the series in mice, rats, and dogs was determined after i.v. and oral dosing. DprE1-IN-1 shows oral bioavailabilities of 86% and 100% in rats and dogs, respectively. The oral exposures of DprE1-IN-1, assessed in infected animals, shows AUCs ranging from 166 to 240 μM · h, and free plasma concentrations were maintained above the MIC for 10 to 24 h. |
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| Animal model | Rodent model of tuberculosis |
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| Dosages | Oral |
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These protocols are for reference only. InvivoChem does not
independently validate these methods.
Preparing Stock Solutions
| Solvent volume to be added |
Mass (the weight of a compound) |
| Mother liquor concentration |
1mg | 5mg | 10mg | 20mg |
| 1mM | 2.8138 mL | 14.0691 mL | 28.1381 mL | 56.2762 mL |
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| 5mM | 0.5628 mL | 2.8138 mL | 5.6276 mL | 11.2552 mL |
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| 10mM | 0.2814 mL | 1.4069 mL | 2.8138 mL | 5.6276 mL |
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| 20mM | 0.1407 mL | 0.7035 mL | 1.4069 mL | 2.8138 mL |
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Quality Control Documentation
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