| Identification | Back Directory | [Name]
GNE140 | [CAS]
2003234-63-5 | [Synonyms]
GNE140
CS-2624
(R)-GNE-140
(R)-GNE-140
(GNE-140
GNE-140;GNE 140;GNE140
(R)-3-((2-chlorophenyl)thio)-4-hydroxy-6-(4-morpholinophenyl)-6-(thiophen-3-yl)-5,6-dihydropyridin-2(1H)-one
2(1H)-Pyridinone, 3-[(2-chlorophenyl)thio]-5,6-dihydro-4-hydroxy-6-[4-(4-morpholinyl)phenyl]-6-(3-thienyl)-, (6R)- | [Molecular Formula]
C25H23ClN2O3S2 | [MOL File]
2003234-63-5.mol | [Molecular Weight]
499.04 |
| Chemical Properties | Back Directory | [Boiling point ]
695.4±55.0 °C(Predicted) | [density ]
1.46±0.1 g/cm3(Predicted) | [storage temp. ]
Keep in dark place,Sealed in dry,2-8°C | [solubility ]
DMSO:14.4(Max Conc. mg/mL);28.9(Max Conc. mM) | [form ]
Solid | [pka]
4.50±1.00(Predicted) | [color ]
Light yellow to yellow | [InChIKey]
SUFXXEIVBZJOAP-RUZDIDTESA-N | [SMILES]
C1(=O)N[C@](C2=CC=C(N3CCOCC3)C=C2)(C2C=CSC=2)CC(O)=C1SC1=CC=CC=C1Cl |
| Hazard Information | Back Directory | [Description]
GNE140 ((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. | [Uses]
(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. | [Biochem/physiol Actions]
GNE-140 is an active site-targeting, potent and selective lactate dehydrogenase (LDH) inhibitor (LDH-A/B/C IC50 = 3/5/5 nM; LDH-A IC50 = 22 nM with mixed GNE-140 diastereomers; malate dehydrogenases MDH1/2 IC50 >10 μM; 301 kinases IC50 >1 μM) that reduces cellular lactate (IC50 = 670 nM; MIA PaCa-2) and upregulates pyruvate levels. GNE-140 affects glycolysis-dependent cancer proliferation (IC50 = 430 nM; MIA PaCa-2 & KP-2) & survival, but not oxidative phosphorylation (OXPHOS)-dependent growth. Due to rapid clearance, GNE-140 is ineffective against MIA PaCa-2 tumor growth with only transient lactate-reducing efficacy in tumor tissue in mice in vivo (100-400 mg/kg b.i.d. p.o.). | [in vivo]
(R)-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] 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. DOI:10.1021/acsmedchemlett.6b00190 |
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| Company Name: |
Twochem Co.Ltd.
|
| Telephone: |
021-58111628 15800915896 |
| Website: |
cn.twochem.com |
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