(R)-GNE-140

(R)-GNE-140 is a potent inhibitor of lactate dehydrogenase (LDH) A, B and C, with IC₅₀ values of 3, 5 and 5 nM against LDHA, LDHB, LDHC, respectively. (R)-GNE-140 blocks the conversion of pyruvate to lactate, reduces lactate production and histone lysine lactylation, and inhibits glycolysis. (R)-GNE-140 attenuates cardiac hypertrophy, alleviates PM_2.5-induced pulmonary inflammation and fibrosis, blocks MRSA-induced Arg1 expression. (R)-GNE-140 is applicable to research related to pathological cardiac hypertrophy, pulmonary fibrosis, MRSA infection and pancreatic cancer^[1][2][3][4]. IC50 & Target:IC50: 3 nM (LDHA), 5 nM (LDHB)^[1] In Vitro:(R)-GNE-140 (10 μM; 48 h) reduces intracellular lactate levels, decreases the surface area of neonatal mouse cardiomyocytes, downregulates the expression of cardiac hypertrophy markers, and inhibits multiple histone lysine lactylation modifications, thereby alleviating angiotensin II (Ang II)-induced hypertrophy of neonatal mouse cardiomyocytes (NMCM)^[1].
Pretreatment of mouse RAW264.7 macrophages with (R)-GNE-140 (10 μM; 4 h) inhibits PM_2.5-induced glycolysis, histone lactylation, pro-fibrotic gene expression and cytokine secretion, and partially reverses macrophage-mediated epithelial-mesenchymal transition (EMT) in MLE-12 cells^[2].
(R)-GNE-140 (6-12 h) inhibits MSM-induced Arg1 mRNA expression in MRSA-infected THP1 cells at 6 h and 12 h post-infection^[3].
(R)-GNE-140 (6-12 h) blocks MSM-induced Arg1 protein expression in THP1 cells infected with MRSA at 6 h and 12 h post-infection^[3].
(R)-GNE-140 (Compound 29-R) can inhibit lactate production in human pancreatic cancer MiaPaca2 cells, with its IC₅₀ being 0.67 μM^[4]. In Vivo:(R)-GNE-140 (5 mg/kg; i.t.; once every other day; 4 weeks) reduces PM_2.5-induced pulmonary inflammation and fibrosis in male C57BL/6 J mice by inhibiting glycolysis and subsequent histone lactylation^[2].