BiochemProbe — Life Science Research Reagents

R-GNE-140 free base · Synonyms: (R)-GNE-140

-GNE-140 is a potent lactate dehydrogenase A inhibitor.

For research use only. Not for human or veterinary use.

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R-GNE-140 structure

CAS No.: 2003234-63-5

Download structure (.mol)

Pack sizes & pricing

Size Price SKU Stock
100 mg USD 540.00 BP-02325-100mg In stock Get quote
250 mg USD 1,080.00 BP-02325-250mg In stock Get quote
500 mg USD 1,728.00 BP-02325-500mg In stock Get quote
1 g USD 2,765.00 BP-02325-1g In stock Get quote
2 g USD 4,423.00 BP-02325-2g In stock Get quote
3 g USD 5,300.00 BP-02325-3g In stock Get quote

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Description

(R)-GNE-140 is a potent lactate dehydrogenase A (LDHA) inhibitor, with IC50s of 3 nM and 5 nM for LDHA and LDHB, respectively; (R)-GNE-140 is 18-fold more potent than S enantiomer.

Biological activity

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). Pretreatment of mouse RAW264.7 macrophages with (R)-GNE-140 (10 μM; 4 h) inhibits PM2.5-induced glycolysis, histone lactylation, pro-fibrotic gene expression and cytokine secretion, and partially reverses macrophage-mediated epithelial-mesenchymal transition (EMT) in MLE-12 cells. (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. (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. (R)-GNE-140 (Compound 29-R) can inhibit lactate production in human pancreatic cancer MiaPaca2 cells, with its IC50 being 0.67 μM. In Vivo (R)-GNE-140 (5 mg/kg; i.t.; once every other day; 4 weeks) reduces PM2.5-induced pulmonary inflammation and fibrosis in male C57BL/6 J mice by inhibiting glycolysis and subsequent histone lactylation.

Identifiers

SMILES
OC1=C(SC2=CC=CC=C2Cl)C(=O)N[C@@](C1)(C1=CSC=C1)C1=CC=C(C=C1)N1CCOCC1
InChIKey
SUFXXEIVBZJOAP-RUZDIDTESA-N

Specifications

MW (average)
499.0450
Formula
C25H23ClN2O3S2
CAS No.
2003234-63-5
Physical state
Solid
Color
Off-white to yellow
Shipping
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
Powder -20℃ 2 years; In solvent -20℃ 1 month;

Solubility

soluble in DMSO

References

[1]. Zhao SS, et al. Lactate regulates pathological cardiac hypertrophy via histone lactylation modification. J Cell Mol Med. 2024;28(16):e70022.
[2]. Li J, et al. Urban airborne PM2.5 induces pulmonary fibrosis through triggering glycolysis and subsequent modification of histone lactylation in macrophages. Ecotoxicol Environ Saf. 2024;273:116162.
[3]. Ma W, et al. Methylsulfonylmethane protects against lethal dose MRSA-induced sepsis through promoting M2 macrophage polarization. Mol Immunol. 2022;146:69-77.
[4]. Purkey HE, et al. Cell Active Hydroxylactam Inhibitors of Human Lactate Dehydrogenase with Oral Bioavailability in Mice. ACS Med Chem Lett. 2016 Aug 26;7(10):896-901.

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