1809794-70-4
Chemical Structure
GNE-140
- CAS No.: 1809794-70-4
- Formula:C25H23ClN2O3S2
- Molecular Weight:499.04
IUPAC Name: 3-((2-chlorophenyl)thio)-4-hydroxy-6-(4-morpholinophenyl)-6-(thiophen-3-yl)-5,6-dihydropyridin-2(1H)-one
InChIKey: SUFXXEIVBZJOAP-UHFFFAOYSA-N
SMILES: O=C1NC(C2=CC=C(N3CCOCC3)C=C2)(CC(O)=C1SC4=C(Cl)C=CC=C4)C5=CSC=C5
Biological Activity: GNE-140 is a racemic mixture of (R)-GNE-140 (HY-100742A) and (S)-GNE-140 (HY-100742B), and it is also the racemate known as GNE-140 racemate (HY-100742). GNE-140 is an LDH inhibitor with IC50 values of 0.003 μM and 0.005 μM against LDHA and LDHB/LDHC, respectively, and also inhibits recombinant human LDH5. GNE-140 reduces lactate production in MIA PaCa-2 cells, inhibits cell proliferation, decreases glucose uptake, and elevates ROS levels, reprogramming cellular metabolic flux toward glycolysis and the pentose phosphate pathway. GNE-140 induces acquired resistance mediated by the AMPK-S6K pathway. GNE-140 inhibits the proliferation of breast cancer cells such as MDA-MB-231, inhibits LDH activity and lactate production in eye organoids, and interferes with early embryonic development in mice. GNE-140 combined with arabinoxylan attenuates intestinal inflammatory injury and improves gut microbiota diversity in choline-fed mice. GNE-140 can be used in research related to cancers such as breast cancer, ocular organ development, embryogenesis, and intestinal inflammatory diseases[1][2][3][4][5][6].
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GNE-140 | GNE-140 is a racemic mixture of (R)-GNE-140 (HY-100742A) and (S)-GNE-140 (HY-100742B), and it is also the racemate known as GNE-140 racemate (HY-100742). GNE-140 is an LDH inhibitor with IC50 values of 0.003 μM and 0.005 μM against LDHA and LDHB/LDHC, respectively, and also inhibits recombinant human LDH5. GNE-140 reduces lactate production in MIA PaCa-2 cells, inhibits cell proliferation, decreases glucose uptake, and elevates ROS levels, reprogramming cellular metabolic flux toward glycolysis and the pentose phosphate pathway. GNE-140 induces acquired resistance mediated by the AMPK-S6K pathway. GNE-140 inhibits the proliferation of breast cancer cells such as MDA-MB-231, inhibits LDH activity and lactate production in eye organoids, and interferes with early embryonic development in mice. GNE-140 combined with arabinoxylan attenuates intestinal inflammatory injury and improves gut microbiota diversity in choline-fed mice. GNE-140 can be used in research related to cancers such as breast cancer, ocular organ development, embryogenesis, and intestinal inflammatory diseases. | |||||||||||||||||||||
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References
- [1]. Takata N, et al. Lactate-dependent transcriptional regulation controls mammalian eye morphogenesis. Nature communications. 2023 Jul 14;14(1):4129. [Content Brief]
- [2]. Boudreau A, et al. Metabolic plasticity underpins innate and acquired resistance to LDHA inhibition. Nature chemical biology. 2016 Oct;12(10):779-86. [Content Brief]
- [3]. Chen X, et al. Lactylation at H3K18 drives pathological angiogenesis via metabolic-epigenetic crosstalk in ischemic retinopathy. Theranostics. 2026;16(15):8650-8668.
- [4]. Nadal-Bufí F, et al. Peptide-based LDH5 inhibitors enter cancer cells and impair proliferation. Cellular and molecular life sciences : CMLS. 2022 Nov 27;79(12):606.
- [5]. Wang Y, et al. PFHpA suppresses zygotic genome activation to drive embryonic arrest: a mechanistic basis for TRAEC strategy-based risk assessment. Journal of Environmental Sciences. 2026 Sep 10:105767.
- [6]. Chen Y, et al. Inhibition of the TLR-TNF-HIF-1α pathway attenuates trimethylamine and inflammation by arabinoxylan and glycolysis inhibitors. Food Bioscience. 2026 Apr 29:108975.