| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
Mycobacterium tuberculosis (Mtb) leucyl-tRNA synthetase (LeuRS)：GSK656 inhibits Mtb LeuRS with an IC50 of 0.20 μM. It shows high selectivity over human mitochondrial and cytoplasmic LeuRS, with IC50 values of >300 μM and 132 μM, respectively. [1]
|
|---|---|
| ln Vitro |
- Antitubercular activity：GSK656 exhibits potent in vitro activity against M. tuberculosis H37Rv with a minimum inhibitory concentration (MIC) of 0.08 μM. [1]
- Enzyme selectivity：The compound demonstrates >1,500-fold selectivity for Mtb LeuRS compared to human cytoplasmic LeuRS, as measured by enzyme inhibition assays. [1] |
| ln Vivo |
- Efficacy in mouse TB model：GSK656 (0.4–10 mg/kg, oral) reduces bacterial burden in the lungs and spleens of M. tuberculosis-infected mice by 2–3 log10 CFU after 14 days of treatment. The ED99 (dose reducing bacterial load by 99%) is 0.4 mg/kg. [1]
- Pharmacokinetics：The compound shows favorable PK properties in mice, including oral bioavailability of 74% and a plasma half-life of 4–6 hours. [1] |
| Enzyme Assay |
Mtb LeuRS inhibition assay：
1. Recombinant Mtb LeuRS is incubated with GSK656 (0.01–10 μM) and radiolabeled leucine ([³H]Leu) in reaction buffer.
2. The formation of Leu-tRNA is measured by nitrocellulose filter binding.
3. IC50 values are calculated from dose-response curves. [1]
|
| Cell Assay |
MIC determination in M. tuberculosis：
1. M. tuberculosis H37Rv cultures are exposed to GSK656 (0.01–10 μM) in Middlebrook 7H9 broth.
2. After 7 days of incubation, bacterial growth is assessed by measuring optical density at 600 nm.
3. The MIC is defined as the lowest concentration preventing visible growth. [1]
|
| Animal Protocol |
Mouse TB infection model：
1. C57BL/6 mice are infected intranasally with M. tuberculosis H37Rv (1×10⁴ CFU).
2. Starting on day 3 post-infection, GSK656 is administered orally (0.4–10 mg/kg) once daily for 14 days.
3. Bacterial load in tissues is determined by plating homogenates on 7H11 agar. [1]
|
| ADME/Pharmacokinetics |
- Absorption: GSK656 is rapidly absorbed in mice, reaching peak plasma concentrations (Cmax) of 1.2–3.5 μM within 1 hour after oral administration. [1]
- Half-life: The plasma half-life in mice is 4–6 hours, supporting once-daily administration. [1] - Bioavailability: The oral bioavailability in mice is 74%, with high plasma protein binding (>99%). [1] - Metabolism: This compound is primarily metabolized through oxidation and glucuronidation, with less than 5% excreted unchanged in urine and feces. [1] |
| Toxicity/Toxicokinetics |
Acute toxicity: No lethal or systemic toxicity was observed in mice after a single oral administration of up to 1000 mg/kg of GSK656. [1]
- Hepatic and renal safety: No significant changes in liver enzymes (ALT, AST) or renal function indicators (BUN, creatinine) were observed in mice treated with therapeutic doses of GSK656. [1] |
| References | |
| Additional Infomation |
Mechanism of action: GSK656 selectively inhibits Mycobacterium tuberculosis leucine synthase (LeuRS), blocking the incorporation of leucine into proteins, thereby disrupting bacterial protein synthesis. [1]
- Clinical development: Due to its high efficacy and good safety profile, this compound has entered the clinical trial stage for the treatment of tuberculosis. [1] |
| Molecular Formula |
C10H13BCLNO4
|
|---|---|
| Molecular Weight |
257.478522062302
|
| Exact Mass |
257.062
|
| Elemental Analysis |
C, 46.65; H, 5.09; B, 4.20; Cl, 13.77; N, 5.44; O, 24.86
|
| CAS # |
2131798-12-2
|
| Related CAS # |
Ganfeborole hydrochloride;2131798-13-3
|
| PubChem CID |
133080621
|
| Appearance |
Typically exists as solid at room temperature
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
17
|
| Complexity |
261
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
B1(C2=C(C=CC(=C2[C@H](O1)CN)Cl)OCCO)O
|
| InChi Key |
DJUOWOXTPXUHDQ-MRVPVSSYSA-N
|
| InChi Code |
InChI=1S/C10H13BClNO4/c12-6-1-2-7(16-4-3-14)10-9(6)8(5-13)17-11(10)15/h1-2,8,14-15H,3-5,13H2/t8-/m1/s1
|
| Chemical Name |
2-[[(3S)-3-(aminomethyl)-4-chloro-1-hydroxy-3H-2,1-benzoxaborol-7-yl]oxy]ethanol
|
| Synonyms |
Ganfeborole; GSK3036656; 2131798-12-2; UNII-KZ8H57WFC7; GSK070 free base; GSK-070 free base; GSK-656 free base; KZ8H57WFC7;
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.8838 mL | 19.4190 mL | 38.8380 mL | |
| 5 mM | 0.7768 mL | 3.8838 mL | 7.7676 mL | |
| 10 mM | 0.3884 mL | 1.9419 mL | 3.8838 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
