GSK2200150A is a novel and potent antimycobacterial agent that has the potential for the treatment of tuberculosis (TB). It has activity against Mycobacterium tuberculosis and Mycobacterium bovis BCG. Tuberculosis afflicts an estimated 2 billion people worldwide and causes 1.3 million deaths annually. Chemotherapeutic solutions rely on drugs developed many years ago, with only one new therapeutic having been approved in the last 40 years. Given the rise of drug-resistant strains, there is an urgent need for the development of a more robust drug development pipeline.
Physicochemical Properties
| Molecular Formula | C20H23NO3S |
| Molecular Weight | 357.466524362564 |
| Exact Mass | 357.139 |
| Elemental Analysis | C, 67.20; H, 6.49; N, 3.92; O, 13.43; S, 8.97 |
| CAS # | 1443138-53-1 |
| PubChem CID | 70689288 |
| Appearance | Solid powder |
| Density | 1.3±0.1 g/cm3 |
| Boiling Point | 503.4±50.0 °C at 760 mmHg |
| Flash Point | 258.2±30.1 °C |
| Vapour Pressure | 0.0±1.3 mmHg at 25°C |
| Index of Refraction | 1.650 |
| LogP | 4.87 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 2 |
| Heavy Atom Count | 25 |
| Complexity | 468 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | S1C=CC2=C1CCOC12CCN(CC2C=CC3=C(C=2)OCCO3)CC1 |
| InChi Key | NCRPMBWORFWNGT-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C20H23NO3S/c1-2-17-18(23-11-10-22-17)13-15(1)14-21-7-5-20(6-8-21)16-4-12-25-19(16)3-9-24-20/h1-2,4,12-13H,3,5-11,14H2 |
| Chemical Name | 1-[(2,3-Dihydro-1,4-benzodioxin-6-yl)methyl]-6',7'-dihydro-spiro[piperidine-4,4'-[4H]thieno[3,2-c]pyran] |
| Synonyms | GSK2200150; GSK-2200150; GSK 2200150; SPIRO; GSK2200150A; GSK-2200150A; GSK 2200150A; |
| 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 | M.tuberculosis strain H37Rv（MIC=0.38 μM） |
| ln Vitro | A brand-new antimycobacterial drug called GSK2200150A works against Mycobacterium tuberculosis.With a minimum inhibitory concentration (MIC) of 0.38 μM, the virulent M. tuberculosis strain H37Rv is the target of GSK2200150A's spirocycle core-containing activities [1]. |
| Cell Assay | In triplicate, GSK2200150A is tested in 96-well microtiter plates at a single concentration of 100 µM or serially diluted in 10 µL of purified H2O. Middlebrook 7H9 complete media, which contains albumin, dextrose, and catalase (ADC), 20% Tween 80, and 50% glycerol, is used to cultivate M. tuberculosis H37Rv. The wells are filled with a 90 µL bacterial suspension with an OD600 nm of 0.001 and incubated for 7 days. Next, add 10 µL of resazurin (0.05% w/v) and incubate for 24 hours at 37°C. Using a FLUOstar Omega microplate reader, measure the fluorescence at 590 nm. The percentage of mycobacterial survival is calculated by subtracting the background fluorescence from each well and comparing the fluorescence of the compound-containing wells to that of the control wells that were not treated with the compound[1]. |
| References |
[1]. Efficient Synthesis and Anti-Tubercular Activity of a Series of Spirocycles: An Exercise in OpenScience. PLoS One. 2014 Dec 10;9(12):e111782. |
Solubility Data
| Solubility (In Vitro) |
DMSO : 65 ~71 mg/mL ( 181.83 ~198.61 mM ) Ethanol : ~18 mg/mL |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.17 mg/mL (6.07 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 21.7 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.17 mg/mL (6.07 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 21.7 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. Solubility in Formulation 3: ≥ 2.17 mg/mL (6.07 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 21.7 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 10% DMSO+40% PEG300+5% Tween-80+45% Saline: ≥ 2.17 mg/mL (6.07 mM) (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7974 mL | 13.9872 mL | 27.9744 mL | |
| 5 mM | 0.5595 mL | 2.7974 mL | 5.5949 mL | |
| 10 mM | 0.2797 mL | 1.3987 mL | 2.7974 mL |