(R)-GNE-140 - CAS 2003234-63-5
Category: Inhibitor
Please be kindly noted products are not for therapeutic use. We do not sell to patients.
Molecular Formula:
Molecular Weight:
(R)-GNE-140 is a potent lactate dehydrogenase A (LDHA) inhibitor (IC50s= 3 nM for LDHA and 5 nM for LDHB), with 18-fold more potent than S enantiomer.
(2R)-5-(2-chlorophenyl)sulfanyl-4-hydroxy-2-(4-morpholin-4-ylphenyl)-2-thiophen-3-yl-1,3-dihydropyridin-6-one; GNE-140
Store in a cool and dry place (or refer to the Certificate of Analysis).
Boiling Point:
695.4±55.0 ℃ at 760 Torr
1.46±0.1 g/cm3
Canonical SMILES:
1.Metabolic plasticity underpins innate and acquired resistance to LDHA inhibition.
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 Nat Chem Biol. 2016 Oct;12(10):779-86. doi: 10.1038/nchembio.2143. Epub 2016 Aug 1.
Metabolic reprogramming in tumors represents a potential therapeutic target. Herein we used shRNA depletion and a novel lactate dehydrogenase (LDHA) inhibitor, GNE-140, to probe the role of LDHA in tumor growth in vitro and in vivo. In MIA PaCa-2 human pancreatic cells, LDHA inhibition rapidly affected global metabolism, although cell death only occurred after 2 d of continuous LDHA inhibition. Pancreatic cell lines that utilize oxidative phosphorylation (OXPHOS) rather than glycolysis were inherently resistant to GNE-140, but could be resensitized to GNE-140 with the OXPHOS inhibitor phenformin. Acquired resistance to GNE-140 was driven by activation of the AMPK-mTOR-S6K signaling pathway, which led to increased OXPHOS, and inhibitors targeting this pathway could prevent resistance. Thus, 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.
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CAS 2003234-63-5 (R)-GNE-140

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