R-GNE-140


Catalog No. size PriceQuantity
M7056-2 2mg solid $100
M7056-10 10mg solid $416

Description

Cas:2003234-63-5 (R-isomer)

Product Information

R-GNE-140 a novel potent lactate dehydrogenase (LDHA) inhibitor with IC50 3nM for LDHA and 5 nM for LDHB. 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 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

 

Synonym:

 

  • GNE-140

  • (R)-GNE-140

  • GNE 140

  • GNE140

 

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

 

InChi Key:

SUFXXEIVBZJOAP-RUZDIDTESA-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)/t25-/m1/s1

 

Smiles Code:

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

 

 

Technical Data:

 

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

 

In Vitro:

  • -GNE-140 inhibits proliferation in 37 of 347 cancer cell lines tested at a potency cut off of 5 μM. (R)-GNE-140 shows inhibitory effect on two chondrosarcoma (bone) cancer cell lines that harbor IDH1 mutations, with IC50 of 0.8 μM.

 

In Vivo:

  • -GNE-140 (5 mg/kg) has high bioavailability in mice. At higher oral doses, ranging from 50 to 200 mg/kg, (R)-GNE-140 displays greater exposure.

 

 

References

 

  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.

 

Products are for research use only. Not for human use.

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