Ganfeborole (GSK656 free base) is a potent, selective and orally bioactive inhibitor of M. tuberculosis (TB) leucyl-tRNA synthetase with IC50 of 0.20 μM. Ganfeborole may be used in tuberculosis (TB)-related research.

Physicochemical Properties

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)

Biological Activity

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, achieving peak plasma concentrations (Cmax) of 1.2–3.5 μM within 1 hour after oral administration. [1] - Half-life：The plasma half-life is 4–6 hours in mice, supporting once-daily dosing. [1] - Bioavailability：Oral bioavailability in mice is 74%, with high plasma protein binding (>99%). [1] - Metabolism：The compound is primarily metabolized via oxidation and glucuronidation, with <5% excreted unchanged in urine and feces. [1]
Toxicity/Toxicokinetics	- Acute toxicity：Single oral doses of GSK656 up to 1,000 mg/kg in mice show no signs of lethality or systemic toxicity. [1] - Liver and kidney safety：No significant changes in liver enzymes (ALT, AST) or renal function markers (BUN, creatinine) are observed in mice treated with GSK656 at therapeutic doses. [1]
References	[1]. Discovery of a Potent and Specific M. tuberculosis Leucyl-tRNA Synthetase Inhibitor: (S)-3-(Aminomethyl)-4-chloro-7-(2-hydroxyethoxy)benzo[c][1,2]oxaborol-1(3H)-ol (GSK656). J Med Chem. 2017 Oct 12;60(19):8011-8026.
Additional Infomation	- Mechanism of action：GSK656 selectively inhibits Mtb LeuRS, blocking leucine incorporation into proteins and disrupting bacterial protein synthesis. [1] - Clinical development：The compound has advanced to clinical trials for the treatment of tuberculosis, leveraging its high potency and favorable safety profile. [1]

Solubility Data

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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (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.