Synonym
R-GNE-140; (R)-GNE-140; GNE 140; GNE140.
IUPAC/Chemical Name
(R)-3-((2-Chlorophenyl)thio)-4-hydroxy-6-(4-morpholinophenyl)-6-(thiophen-3-yl)-5,6-dihydropyridin-2(1H)-one
InChi Key
SUFXXEIVBZJOAP-RUZDIDTESA-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)/t25-/m1/s1
SMILES Code
O=C1C(SC2=CC=CC=C2Cl)=C(O)C[C@](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
More Info
Metabolic reprogramming in tumors represents a potential therapeutic target. combining an LDHA inhibitor with compounds targeting the mitochondrial or AMPK-S6K signaling axis may not only broaden the clinical utility of LDHA inhibitors beyond glycolytically dependent tumors but also reduce the emergence of resistance to LDHA inhibition.
Biological target:
(R)-GNE-140 is a potent lactate dehydrogenase A (LDHA) inhibitor, with IC50s of 3 nM and 5 nM for LDHA and LDHB, respectively.
In vitro activity:
This study treated WT and LDHA/B-DKO cells with different concentrations of GNE-140 and showed that a concentration of 10 μm, known to collapse LDHA and B activity, reduced the growth of the WT but not of the two LDHA/B-DKO cell lines reported here (Fig. 8, A–D). This long-term experiment (9 to 12 days) proved the lack of off-target effects of this compound at the concentration used. As shown in Fig. 8, E–H, 1-h treatment with 10 μm GNE-140 was sufficient to phenocopy the effect of the LDHA/B-DKO cells in terms of suppression of glycolysis and reactivation of OXPHOS. Hence, the growth phenotype of DLHA/B-DKO cells does not result from long-term growth selection during the two steps of genetic disruption. This finding, based on genetics and specific pharmacological disruption of LDHA and LDHB, firmly attests that, under normoxia, the Warburg effect is dispensable for in vitro tumor growth.
Reference: J Biol Chem. 2018 Oct 12; 293(41): 15947–15961. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6187639/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
14.4 |
28.90 |
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
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. Ždralević M, Brand A, Di Ianni L, Dettmer K, Reinders J, Singer K, Peter K, Schnell A, Bruss C, Decking SM, Koehl G, Felipe-Abrio B, Durivault J, Bayer P, Evangelista M, O'Brien T, Oefner PJ, Renner K, Pouysségur J, Kreutz M. Double genetic disruption of lactate dehydrogenases A and B is required to ablate the "Warburg effect" restricting tumor growth to oxidative metabolism. J Biol Chem. 2018 Oct 12;293(41):15947-15961. doi: 10.1074/jbc.RA118.004180. Epub 2018 Aug 29. PMID: 30158244; PMCID: PMC6187639.
In vitro protocol:
1. Ždralević M, Brand A, Di Ianni L, Dettmer K, Reinders J, Singer K, Peter K, Schnell A, Bruss C, Decking SM, Koehl G, Felipe-Abrio B, Durivault J, Bayer P, Evangelista M, O'Brien T, Oefner PJ, Renner K, Pouysségur J, Kreutz M. Double genetic disruption of lactate dehydrogenases A and B is required to ablate the "Warburg effect" restricting tumor growth to oxidative metabolism. J Biol Chem. 2018 Oct 12;293(41):15947-15961. doi: 10.1074/jbc.RA118.004180. Epub 2018 Aug 29. PMID: 30158244; PMCID: PMC6187639.
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.
