dpre1

DprE1-IN-2 is an effective DprE1 inhibitor.

DprE1-IN-1 is a potent, orally active DprE1 inhibitor that demonstrates good hepatocyte stability, low cytotoxicity, and low hERG channel inhibition. It also exhibits effective anti-branched bacilli activity in macrophages, reducing the bacterial load by 1.29 log10 CFU.

DprE1-IN-13 (Compound 42) is an inhibitor of decaprenyl-phosphoryl-β-d-ribose oxidase (DprE1) with an IC50 value of 12.72 μM. It effectively inhibits Mycobacterium tuberculosis H37Ra, with a MIC50 of 1.071 μM.

DprE1-IN-5 (Compound 10), a potent DprE1 inhibitor, exhibits anti-TB activity with an MIC of 4 μM against the Mtb H37Rv strain and demonstrates antimycobacterial efficacy against drug-resistant strains. Additionally, it possesses high microsomal stability [1].

DprE1-IN-7 (Compound 64) is a DprE1 inhibitor with potent anti-tuberculosis (TB) activity, demonstrating a minimum inhibitory concentration (MIC) of 1 μM against the Mtb H37Rv strain. It exhibits antimycobacterial effects on drug-resistant strains, shows high microsomal stability, and has medium clearance [1].

DprE1-IN-4 is a potent, non-covalent inhibitor of DprE1 (IC50: 0.90 μg mL). DprE1-IN-4 has acceptable pharmacokinetic properties and has a significant bactericidal effect in a mouse model of acute tuberculosis.

DprE1-IN-11 (compound 3) is an orally active DprE1 inhibitor that exhibits antitubercular activity against both MTB H37Rv and MDR-MTB strains (MIC <0.029-0.095 μM).

DprE1-IN-377790 is a novel DprE1 inhibitor, killing M. tuberculosis.

DprE1-IN-9 (compound B18) is an efficient, reversible inhibitor of DprE1, interacting with the enzyme's receptor cavity. It exhibits potent antimycobacterial properties, demonstrating activity against non-pathogenic H37Ra (MIC=0.18 µg mL) and pathogenic strains, including H37Rv, as well as clinical MDR and XDR isolates [1].

DprE1-IN-8, a potent DprE1 inhibitor with an IC50 of less than 0.75 μM, demonstrates significant activity against Mtb H37Rv, with an IC50 of 6 nM, making it applicable in tuberculosis research [1].

DprE1-IN-6 (Compound 56) is a DprE1 inhibitor with anti-TB activity, showing a minimum inhibitory concentration (MIC) of 1 μM against the Mtb H37Rv strain and efficacy against drug-resistant mycobacterial strains. Additionally, it has high microsomal stability and medium clearance [1].

TBA-7371 (DprE1-IN-1) is a potent inhibitor of DprE1 and PDE6.

BTZ043 Racemate (Benzothiazinone 10526038) is a decaprenylphosphoryl-β-D-ribose 2'-epimerase (DprE1) inhibitor, used as a new antimycobacterial agent.

Macozinone (PBTZ169) inhibits decaprenylphosphoryl-β-d-ribose 2′-oxidase (DprE1), more efficiently than BTZ043.

BTZ043 is a DprE1 inhibitor with nanomolar bactericidal activity against Mycobacterium tuberculosis in vitro.

OPC-167832 is a potent and orally active dprE1 Inhibitor with an IC50 of 0.258 μM. OPC-167832 has antituberculosis activity and can be used for the research of tuberculosis caused by Mycobacterium tuberculosis[1]. OPC-167832 exhibits very low MICs against laboratory strains of M. tuberculosis H37Rv (MIC: 0.0005 μg/ml) and Kurono (MIC: 0.0005 μg/ml) and strains with monoresistance to rifampin (RIF), isoniazid (INH), ethambutol (EMB), streptomycin (STR), and pyrazinamide (PZA) (MIC: 0.00024-0.001 μg/ml). However, OPC-167832 has minimal or no activity against standard strains of nonmycobacterial aerobic and anaerobic bacteria[1].The IC90 values of OPC-167832 against intracellular M. tuberculosis strains H37Rv and Kurono are 0.0048 and 0.0027 μg/ml, respectively. OPC-167832 shows bactericidal activity against intracellular M. tuberculosis at a low concentration, and the bactericidal activity is saturated at concentrations of 0.004 μg/ml or higher[1]. OPC-167832 (oral administration; 0.625-10 mg/kg) exhibits a good pharmacokinetic characteristic. The plasma reaches peak at 0.5 h to 1.0 h (tmax) and is eliminated with a half-life (t1/2) of 1.3 h to 2.1 h OPC-167832 distribution in the lungs is approximately 2 times higher than that in plasma, and the Cmax and AUCt of OPC-167832 in plasma and the lungs shows dose dependency[1].OPC-167832 (oral administration; 0.625-10 mg/kg; 4 weeks) significantly reduces lung CFU compared to the vehicle group. The dose-dependent decrease of lung CFU is observed from 0.625 mg/kg to 2.5 mg/kg. In a M. tuberculosis Kurono-infected ICR female mice model. OPC-167832 combines with DMD, BDQ, or LVX via oral gavage exhibits significantly higher efficacies than each single agent alone[1].[1].OPC-167832 (oral gavage; 2.5 mg/kg; combination with DCMB; 12 weeks) demonstrates the most potent efficacy when compares with DC, DCB. The lung CFU count after 6 weeks of treatment is below the detection limit, and at the end of just 8 weeks of treatment, the bacteria in the lungs of all the evaluated mice had already been eradicate[1]. [1]. Norimitsu Hariguchi, et al. OPC-167832, a Novel Carbostyril Derivative with Potent Antituberculosis Activity as a DprE1 Inhibitor.Antimicrob Agents Chemother. 2020 May 21;64(6):e02020-19.

Antitubercular agent-31 is an antitubercular agent that inhibits M. tuberculosisH37Rv (MIC: 0.03 μM) and also inhibits DprE1 (IC50: 1.1 μM).

Cmpd 339509 is a DprE1 inhibitor. DprE1 is an epimerase required for cell wall biosynthesis.

Antitubercular agent-32 is a Benzothiazinone derivative that inhibits Mycobacterium tuberculosis and exhibits good metabolic stability and water solubility. Antitubercular agent-32 can act on decaprenylphosphoryl-β-D-ribose 2'-oxidase (DprE1, IC50: 3.9 μM) and exhibits antitubercular effects.

Antimycobacterial agent-6 (compound 25) effectively inhibits Mycobacterium tuberculosis, including wild-type and fluoroquinolone-resistant strains, by targeting the Mtb DprE1-C387S mutant, with minimal inhibitory concentrations (MIC90) of 0.9 μM for H37Rv and MoxR strains, and 0.5 μM for the DprE1-P116S strain [1].

TCA1 (TCA 1) is a small molecule with activity against drug-resistant and persistent tuberculosis.