Synonym
GSK070; GSK-070; GSK 070; GSK3036656; GSK-3036656; GSK 3036656; GSK656; GSK-656; GSK 656; GSK656 HCl; GSK656 hydrochloride; Ganfeborole HCl
IUPAC/Chemical Name
(S)‑3-(Aminomethyl)-4-chloro-7-(2-hydroxyethoxy)benzo[c][1,2]oxaborol-1(3H)‑ol hydrochloride
InChi Key
FUOKBESTQMGROA-DDWIOCJRSA-N
InChi Code
InChI=1S/C10H13BClNO4.ClH/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;1H/t8-;/m1./s1
SMILES Code
OB1O[C@H](CN)C2=C(Cl)C=CC(OCCO)=C12.[H]Cl
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
There is an urgent need to develop new and safer antitubercular agents that possess a novel mode of action.
Biological target:
GSK656 is a potent antitubercular agent, acting as an inhibitor of Mycobacterium tuberculosis (Mtb) leucyl-tRNA synthetase (LeuRS), with an IC50 of 0.2 μM.
In vitro activity:
In contrast, GSK656 showed excellent activity against M. abscessus isolates; all isolates had MICs of ≤0.25 mg/liter, yielding a MIC50 of 0.031 mg/liter and a MIC90 of 0.063 mg/liter, which were 2-fold lower than those for M. tuberculosis isolates.
Reference: Antimicrob Agents Chemother. 2020 Jan 27;64(2):e01577-19. https://pubmed.ncbi.nlm.nih.gov/31791947/
In vivo activity:
Further evaluation of these Mtb LeuRS inhibitors by in vivo pharmacokinetics (PK) and murine tuberculosis (TB) efficacy models led to the discovery of GSK3036656 (abbreviated as GSK656). This molecule shows potent inhibition of Mtb LeuRS (IC50 = 0.20 μM) and in vitro antitubercular activity (Mtb H37Rv MIC = 0.08 μM). Additionally, it is highly selective for the Mtb LeuRS enzyme with IC50 of >300 μM and 132 μM for human mitochondrial LeuRS and human cytoplasmic LeuRS, respectively. In addition, it exhibits remarkable PK profiles and efficacy against Mtb in mouse TB infection models with superior tolerability over initial leads.
Reference: J Med Chem. 2017 Oct 12;60(19):8011-8026. https://pubmed.ncbi.nlm.nih.gov/28953378/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
67.5 |
229.64 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
293.94
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Dong W, Li S, Wen S, Jing W, Shi J, Ma Y, Huo F, Gao F, Pang Y, Lu J. In Vitro Susceptibility Testing of GSK656 against Mycobacterium Species. Antimicrob Agents Chemother. 2020 Jan 27;64(2):e01577-19. doi: 10.1128/AAC.01577-19. PMID: 31791947; PMCID: PMC6985724.
2. Li X, Hernandez V, Rock FL, Choi W, Mak YSL, Mohan M, Mao W, Zhou Y, Easom EE, Plattner JJ, Zou W, Pérez-Herrán E, Giordano I, Mendoza-Losana A, Alemparte C, Rullas J, Angulo-Barturen I, Crouch S, Ortega F, Barros D, Alley MRK. 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. doi: 10.1021/acs.jmedchem.7b00631. Epub 2017 Sep 27. PMID: 28953378.
In vitro protocol:
1. Dong W, Li S, Wen S, Jing W, Shi J, Ma Y, Huo F, Gao F, Pang Y, Lu J. In Vitro Susceptibility Testing of GSK656 against Mycobacterium Species. Antimicrob Agents Chemother. 2020 Jan 27;64(2):e01577-19. doi: 10.1128/AAC.01577-19. PMID: 31791947; PMCID: PMC6985724.
In vivo protocol:
1. Li X, Hernandez V, Rock FL, Choi W, Mak YSL, Mohan M, Mao W, Zhou Y, Easom EE, Plattner JJ, Zou W, Pérez-Herrán E, Giordano I, Mendoza-Losana A, Alemparte C, Rullas J, Angulo-Barturen I, Crouch S, Ortega F, Barros D, Alley MRK. 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. doi: 10.1021/acs.jmedchem.7b00631. Epub 2017 Sep 27. PMID: 28953378.
1: Li X, Hernandez V, Rock FL, Choi W, Mak YSL, Mohan M, Mao W, Zhou Y, Easom EE,
Plattner JJ, Zou W, Pérez-Herrán E, Giordano I, Mendoza-Losana A, Alemparte C,
Rullas J, Angulo-Barturen I, Crouch S, Ortega F, Barros D, Alley MRK. 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 Sep 27. doi: 10.1021/acs.jmedchem.7b00631. [Epub ahead
of print] PubMed PMID: 28953378.
