BWC0977 formic
Based on 1 Customer Validation
BWC0977 formic acts as an inhibitor of bacterial Topoisomerase. BWC0977 formic stabilizes single-strand DNA breaks, inhibits DNA supercoiling and decatenation activities, binds to GyrA and ParC residues, and activates the SOS response. BWC0977 formic can be used in research related to multidrug-resistant bacterial infections.
For research use only. We do not sell to patients.
- Purity: 99.61%
- CAS No.: 3027162-72-4
- Formula: C23H23FN6O7
- Molecular Weight:514.46
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Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
Biological Activity
Description
IC50 & Target
|
Topoisomerase II |
Cellular Effect
|
Cell Line
|
Type | Value | Description | References |
|---|---|---|---|---|
| CHO | IC50 |
131 μM
|
Inhibition of hERG potassium channel activity stably expressed in Chinese hamster ovary cells measured after 2 min incubation by automated patch-clamp assay (QPatch HTX platform).
Inhibition of hERG potassium channel activity stably expressed in Chinese hamster ovary cells measured after 2 min incubation by automated patch-clamp assay (QPatch HTX platform).
|
39294149 |
In Vitro
BWC0977 (compound 13) (0.03-2 μg/mL) formic strongly inhibits the growth of multidrug-resistant Gram-negative and Gram-positive bacteria, with an MIC90 range of 0.03-2 μg/mL[1].
BWC0977 (0.015-40 μg/mL; up to 10 hours) formic exhibits time-dependent bactericidal activity against clinical isolates of E. coli, A. baumannii, K. pneumoniae, and P. aeruginosa[2].
BWC0977 (0.1 nM-1 mM; 40 min) formic potently inhibits the supercoiling activity of wild-type E. coli DNA gyrase, with an IC50 of 4 nM[4].
BWC0977 (200 μM; 8 h) formic acts via intercalation and specific interactions with ParC residues D79, M118 and R119[4].
BWC0977 (0.01-7.5 μg/mL; 16-18 h) formic inhibits the growth of wild-type E. coli MG1655, with an MIC of 0.03 μg/mL[4].
BWC0977 (0.007-1 μg/mL; 16-18 h) formic exhibits potent antibacterial activity against a variety of drug-susceptible and multidrug-resistant Gram-positive and Gram-negative bacterial isolates[4].
BWC0977 (pre-incubated at 24°C for 10 min; reacted at 37°C for 40 min) formic potently inhibits the supercoiling activity of E. coli DNA gyrase and the decatenation activity of topoisomerase IV[3].
In automated patch-clamp assays, BWC0977 (6-point serial dilutions up to 300 μM; 2 min) formic inhibits hERG ion channel activity with an IC50 of 131 μM, while in manual patch-clamp assays, the IC50 is 49.7 μM[3].
BWC0977 formic is a substrate of human MATE2-K and OAT3 transporters, with Km values of 469 μM and 121 μM, respectively[3].
BWC0977 (> 200 μM) formic exhibits over 5000-fold higher selectivity for bacterial type II topoisomerases than for human topoisomerase IIα and IIβ. Its IC50 against human topoisomerase IIα is 113 μM, and no detectable inhibitory effect on human topoisomerase IIβ is observed at the highest concentration of 200 μM[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Parmacokinetics
In Vivo
BWC0977 (40-160 mg/kg; subcutaneous injection; every 6-24 hours; 1-4 doses) formic exhibits dose-dependent bactericidal efficacy in a neutropenic mouse thigh infection model, with an ED50 of 58 mg/kg when administered every 8 hours[3].
BWC0977 (3-450 mg/kg; intravenous injection; administered every 8-24 hours within 24 hours) formic exhibits bactericidal activity against various multidrug-resistant (MDR) pathogens in a neutropenic rat model of pulmonary infection[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:CD-1 (male, neutropenic)[3]
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Dosage:40, 80, 160, mg/kg
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Administration:s.c.; every 6 hours for 4 doses; every 12 hours for 2 doses; every 24 hours for 1 dose
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Result:Showed equivalent efficacy across fractionated dosing regimens (160 mg/kg q24h, 80 mg/kg q12h, 40 mg/kg q6h).
Demonstrated dose-dependent logarithmic bacterial killing against multiple wild-type and MDR isolates.
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Animal Model:Wistar (male, neutropenic)[3]
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Dosage:3, 5, 10, 20, 30, 40, 75, 100, 150, 300, 350, 400, 450 mg/kg
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Administration:i.v.; 2-hour infusion; every 8-24 hours over 24-hour period; constant rate infusion over 2 hours
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Result:Demonstrated bactericidal dose-response against multiple MDR isolates.
Showed the strongest correlation with efficacy.
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date |
Phase
|
|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 3027162-72-4
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Appearance Solid
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Molecular Weight 514.46
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Formula C23H23FN6O7
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Color White to off-white
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SMILES
O=C1N(C)C2=C(CCNC[C@H]3CN(C4=CN=C(OCC(N5)=O)C5=N4)C(O3)=O)C(F)=CC=C2C=C1.OC=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvent & Solubility
In Vitro:
DMSO : 4.17 mg/mL (8.11 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Purity & Documentation
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Data Sheet (291 KB)
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SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Korean - KR (251 KB)
- Portuguese - PT (251 KB)
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Handling Instructions (2659 KB)
References
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.9438 mL | 9.7189 mL | 19.4379 mL | 48.5946 mL |
| 5 mM | 0.3888 mL | 1.9438 mL | 3.8876 mL | 9.7189 mL |