Synonym
GNE-140 racemic; GNE-140; GNE 140; GNE140.
IUPAC/Chemical Name
3-((2-Chlorophenyl)thio)-4-hydroxy-6-(4-morpholinophenyl)-6-(thiophen-3-yl)-5,6-dihydropyridin-2(1H)-one
InChi Key
SUFXXEIVBZJOAP-UHFFFAOYSA-N
InChi Code
InChI=1S/C25H23ClN2O3S2/c26-20-3-1-2-4-22(20)33-23-21(29)15-25(27-24(23)30,18-9-14-32-16-18)17-5-7-19(8-6-17)28-10-12-31-13-11-28/h1-9,14,16,29H,10-13,15H2,(H,27,30)
SMILES Code
O=C1C(SC2=CC=CC=C2Cl)=C(O)CC(C3=CSC=C3)(C4=CC=C(N5CCOCC5)C=C4)N1
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
Biological target:
GNE-140 racemic is a novel potent lactate dehydrogenase (LDHA) inhibitor.
In vitro activity:
In this work, the effects of GNE-140 were evaluated over a concentration dose range in MDA-MB-231 cells with data being collected for lactic acid produced and glucose consumed. The findings in this study clearly demonstrate that GNE-140 can effectively block lactic acid production, inverse to hampered utilization of glucose, suggesting an attenuated rate of glycolysis (Figure 2A).
Reference: Biomolecules. 2021 Nov 24;11(12):1751. https://pubmed.ncbi.nlm.nih.gov/34944395/
In vivo activity:
GNE-140, the LDHA-specific inhibitor of glycolysis, blocked the MSM-induced Arg1 expression in this mouse disease model.
Reference: Mol Immunol. 2022 Jun;146:69-77. https://pubmed.ncbi.nlm.nih.gov/35461144/
Preparing Stock Solutions
The following data is based on the
product
molecular weight
499.04
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. Mazzio E, Mack N, Badisa RB, Soliman KFA. Triple Isozyme Lactic Acid Dehydrogenase Inhibition in Fully Viable MDA-MB-231 Cells Induces Cytostatic Effects That Are Not Reversed by Exogenous Lactic Acid. Biomolecules. 2021 Nov 24;11(12):1751. doi: 10.3390/biom11121751. PMID: 34944395; PMCID: PMC8698706.
2. Schwab M, Thunborg K, Azimzadeh O, von Toerne C, Werner C, Shevtsov M, Di Genio T, Zdralevic M, Pouyssegur J, Renner K, Kreutz M, Multhoff G. Targeting Cancer Metabolism Breaks Radioresistance by Impairing the Stress Response. Cancers (Basel). 2021 Jul 27;13(15):3762. doi: 10.3390/cancers13153762. PMID: 34359663; PMCID: PMC8345170.
3. Ma W, Ao S, Zhou J, Li J, Liang X, Yang X, Zhang H, Liu B, Tang W, Liu H, Xiao H, Liang H, Yang X. Methylsulfonylmethane protects against lethal dose MRSA-induced sepsis through promoting M2 macrophage polarization. Mol Immunol. 2022 Jun;146:69-77. doi: 10.1016/j.molimm.2022.04.001. Epub 2022 Apr 20. PMID: 35461144.
In vitro protocol:
1. Mazzio E, Mack N, Badisa RB, Soliman KFA. Triple Isozyme Lactic Acid Dehydrogenase Inhibition in Fully Viable MDA-MB-231 Cells Induces Cytostatic Effects That Are Not Reversed by Exogenous Lactic Acid. Biomolecules. 2021 Nov 24;11(12):1751. doi: 10.3390/biom11121751. PMID: 34944395; PMCID: PMC8698706.
2. Schwab M, Thunborg K, Azimzadeh O, von Toerne C, Werner C, Shevtsov M, Di Genio T, Zdralevic M, Pouyssegur J, Renner K, Kreutz M, Multhoff G. Targeting Cancer Metabolism Breaks Radioresistance by Impairing the Stress Response. Cancers (Basel). 2021 Jul 27;13(15):3762. doi: 10.3390/cancers13153762. PMID: 34359663; PMCID: PMC8345170.
In vivo protocol:
1. Ma W, Ao S, Zhou J, Li J, Liang X, Yang X, Zhang H, Liu B, Tang W, Liu H, Xiao H, Liang H, Yang X. Methylsulfonylmethane protects against lethal dose MRSA-induced sepsis through promoting M2 macrophage polarization. Mol Immunol. 2022 Jun;146:69-77. doi: 10.1016/j.molimm.2022.04.001. Epub 2022 Apr 20. PMID: 35461144.
1: Boudreau A, Purkey HE, Hitz A, Robarge K, Peterson D, Labadie S, Kwong M, Hong
R, Gao M, Del Nagro C, Pusapati R, Ma S, Salphati L, Pang J, Zhou A, Lai T, Li Y,
Chen Z, Wei B, Yen I, Sideris S, McCleland M, Firestein R, Corson L, Vanderbilt
A, Williams S, Daemen A, Belvin M, Eigenbrot C, Jackson PK, Malek S,
Hatzivassiliou G, Sampath D, Evangelista M, O'Brien T. Metabolic plasticity
underpins innate and acquired resistance to LDHA inhibition. Nat Chem Biol. 2016
Oct;12(10):779-86. doi: 10.1038/nchembio.2143. Epub 2016 Aug 1. PubMed PMID:
27479743.
