| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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OPC-167832 (OPC167832) is a novel carbostyril derivative developed by Otsuka with potent antituberculosis activity, acting as a DprE1 (decaprenylphosphoryl-β-d-ribose 2′-oxidase) Inhibitor. In a mouse model of chronic TB, OPC-167832 showed potent bactericidal activities starting at a dose of 0.625 mg/kg of body weight. Further, it exhibited significant combination effects in 2-drug combinations with delamanid, bedaquiline, or levofloxacin. Finally, 3- or 4-drug regimens comprised of delamanid and OPC-167832 as the core along with bedaquiline, moxifloxacin, or linezolid showed efficacy in reducing the bacterial burden and preventing relapse superior to that of the standard treatment regimen.
| ln Vitro |
The MIC of quodepistat (OPC-167832) against lab strains is extremely low. MIC values for tuberculosis H37Rv (0.0005 μg/ml) and Kurono (0.0005 μg/ml) as well as for monoresistant strains of rifampicin (RIF), isoniazid (INH), ethambutol (EMB), streptomycin (STR), and pyrazinamide (PZA) range from 0.00024 to 0.001 μg/ml. Quabodepistat, however, exhibits negligible or no activity against common anaerobic and aerobic non-mycobacterial bacterial strains [1]. Quabodepistat has IC90 values of 0.0048 and 0.0027 μg/ml against intracellular Mycobacterium TB strains H37Rv and Kurono, respectively. At low doses, quabodepistat exhibits bactericidal action against intracellular Mycobacterium TB; at concentrations of 0.004 μg/ml or above, the bactericidal activity achieves saturation [1].
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| ln Vivo |
Good pharmacokinetic characteristics are exhibited by quabodepistat (OPC-167832) (published article; 0.625-10 mg/kg). With a half-life (t1/2) of 1.3 to 2.1 hours, quabodepistat in the lungs has a dose-dependent Cmax and AUCt that peak at 0.5 to 1.0 hours (tmax)[1]. It also eliminates a 2-fold concentration of quabodepistat in the lungs. Comparing quabodepistat (interface; 0.625–10 mg/kg; 4 weeks) to vehicle resulted in a significant reduction in lung CFU. Lung CFU decreased from 0.625 mg/kg to 2.5 mg/kg in a dose-dependent manner. Infection with M. Kurono in the ICR female model. When Quabodepistat is taken orally in conjunction with DMD, BDQ, or LVX, it works best when taken in combination with other medications [1]. In comparison to DC and DCB, quobedepistat (gavage; 2.5 mg/kg; combined with DCMB; 12 weeks) demonstrated the most efficacious treatment. CFU counts in the lungs following 6 weeks of treatment were below the limit of detection, while by the completion of the standard 8 weeks of treatment, all evaluated bacteria had been eliminated from the lungs of all mice [1].
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| Animal Protocol |
Animal/Disease Models: ICR mouse[1]
Doses: 0.625-10 mg/kg Route of Administration: Oral; 0.625-10 mg/kg; 4 weeks Experimental Results: Demonstrated in vivo efficacy in mouse chronic tuberculosis model. |
| References |
[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.
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| Molecular Formula |
C21H20CLF3N2O4
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|---|---|
| Molecular Weight |
456.8462
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| Exact Mass |
456.106
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| CAS # |
1883747-71-4
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| PubChem CID |
118904282
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| Appearance |
White to light yellow solid powder
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| Density |
1.485±0.06 g/cm3(Predicted)
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| Boiling Point |
645.6±55.0 °C(Predicted)
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| LogP |
2.5
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
31
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| Complexity |
652
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| Defined Atom Stereocenter Count |
2
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| SMILES |
ClC1C=C(C(=C(C=1)F)N1CC[C@@](COC2C=CC(=C3C=2CCC(N3)=O)F)([C@@H](C1)O)O)F
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| InChi Key |
XZISSTDXPBUCJA-DYESRHJHSA-N
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| InChi Code |
InChI=1S/C21H20ClF3N2O4/c22-11-7-14(24)20(15(25)8-11)27-6-5-21(30,17(28)9-27)10-31-16-3-2-13(23)19-12(16)1-4-18(29)26-19/h2-3,7-8,17,28,30H,1,4-6,9-10H2,(H,26,29)/t17-,21-/m1/s1
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| Chemical Name |
5-(((3R,4R)-1-(4-chloro-2,6-difluorophenyl)-3,4-dihydroxypiperidin-4-yl)methoxy)-8-fluoro-3,4-dihydroquinolin-2(1H)-one
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| Synonyms |
OPC 167832 OPC167832OPC-167832
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~180 mg/mL (~394.01 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 4.5 mg/mL (9.85 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 45.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1889 mL | 10.9445 mL | 21.8890 mL | |
| 5 mM | 0.4378 mL | 2.1889 mL | 4.3778 mL | |
| 10 mM | 0.2189 mL | 1.0945 mL | 2.1889 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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