GNE-140 racemic | CAS#1809794-70-4 | LDHA inhibitor

MedKoo Cat#: 526381 | Name: GNE-140 racemic

Description:

WARNING: This product is for research use only, not for human or veterinary use.

GNE-140 racemic is a novel potent lactate dehydrogenase (LDHA) inhibitor. 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.

Chemical Structure

GNE-140 racemic

CAS#1809794-70-4 (racemic)

Theoretical Analysis

MedKoo Cat#: 526381

Name: GNE-140 racemic

CAS#: 1809794-70-4 (racemic)

Chemical Formula: C25H23ClN2O3S2

Exact Mass: 498.0839

Molecular Weight: 499.04

Elemental Analysis: C, 60.17; H, 4.65; Cl, 7.10; N, 5.61; O, 9.62; S, 12.85

Price and Availability

Size	Price	Availability
50mg	USD 450.00	2 Weeks
100g	USD 750.00	2 Weeks
200mg	USD 1,250.00	2 Weeks
1g	USD 4,250.00	2 Weeks

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Related CAS #

2003234-63-5 (R-isomer) 1809794-70-4 (racemic) 2003234-64-6 (S-isomer)

Synonym

GNE-140 racemic; GNE-140; GNE 140; GNE140.

IUPAC/Chemical Name

3-((2-Chlorophenyl)thio)-4-hydroxy-6-(4-morpholinophenyl)-6-(thiophen-3-yl)-5,6-dihydropyridin-2(1H)-one

InChi Key

SUFXXEIVBZJOAP-UHFFFAOYSA-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)

SMILES Code

O=C1C(SC2=CC=CC=C2Cl)=C(O)CC(C3=CSC=C3)(C4=CC=C(N5CCOCC5)C=C4)N1

Appearance

Solid powder

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

Product Data

Product Data

Instruction

View handling instruction

Biological target:

GNE-140 racemic is a novel potent lactate dehydrogenase (LDHA) inhibitor.

In vitro activity:

In this work, the effects of GNE-140 were evaluated over a concentration dose range in MDA-MB-231 cells with data being collected for lactic acid produced and glucose consumed. The findings in this study clearly demonstrate that GNE-140 can effectively block lactic acid production, inverse to hampered utilization of glucose, suggesting an attenuated rate of glycolysis (Figure 2A). Reference: Biomolecules. 2021 Nov 24;11(12):1751. https://pubmed.ncbi.nlm.nih.gov/34944395/

In vivo activity:

GNE-140, the LDHA-specific inhibitor of glycolysis, blocked the MSM-induced Arg1 expression in this mouse disease model. Reference: Mol Immunol. 2022 Jun;146:69-77. https://pubmed.ncbi.nlm.nih.gov/35461144/

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. Mazzio E, Mack N, Badisa RB, Soliman KFA. Triple Isozyme Lactic Acid Dehydrogenase Inhibition in Fully Viable MDA-MB-231 Cells Induces Cytostatic Effects That Are Not Reversed by Exogenous Lactic Acid. Biomolecules. 2021 Nov 24;11(12):1751. doi: 10.3390/biom11121751. PMID: 34944395; PMCID: PMC8698706. 2. Schwab M, Thunborg K, Azimzadeh O, von Toerne C, Werner C, Shevtsov M, Di Genio T, Zdralevic M, Pouyssegur J, Renner K, Kreutz M, Multhoff G. Targeting Cancer Metabolism Breaks Radioresistance by Impairing the Stress Response. Cancers (Basel). 2021 Jul 27;13(15):3762. doi: 10.3390/cancers13153762. PMID: 34359663; PMCID: PMC8345170. 3. Ma W, Ao S, Zhou J, Li J, Liang X, Yang X, Zhang H, Liu B, Tang W, Liu H, Xiao H, Liang H, Yang X. Methylsulfonylmethane protects against lethal dose MRSA-induced sepsis through promoting M2 macrophage polarization. Mol Immunol. 2022 Jun;146:69-77. doi: 10.1016/j.molimm.2022.04.001. Epub 2022 Apr 20. PMID: 35461144.

In vitro protocol:

In vivo protocol:

1. Ma W, Ao S, Zhou J, Li J, Liang X, Yang X, Zhang H, Liu B, Tang W, Liu H, Xiao H, Liang H, Yang X. Methylsulfonylmethane protects against lethal dose MRSA-induced sepsis through promoting M2 macrophage polarization. Mol Immunol. 2022 Jun;146:69-77. doi: 10.1016/j.molimm.2022.04.001. Epub 2022 Apr 20. PMID: 35461144.

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.