GNE140

Synonym(s):(6R)-3-[(2-Chlorophenyl)thio]-5,6-dihydro-4-hydroxy-6-[4-(4-morpholinyl)phenyl]-6-(3-thienyl)-2(1H)-pyridinone;(R)-3-(2-Chlorophenyl)sulfanyl-6-(4-morpholinophenyl)-6-(3-thienyl)piperidine-2,4-dione;GNE 140;GNE140

CAS NO.：2003234-63-5
Empirical Formula: C25H23ClN2O3S2
Molecular Weight: 499.04
Update Date: 2024-07-02 08:55:09

What is GNE140?

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.

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.).

Properties of GNE140

Boiling point:	695.4±55.0 °C(Predicted)
Density	1.46±0.1 g/cm3(Predicted)
storage temp.	2-8°C(protect from light)
solubility	DMSO:14.4(Max Conc. mg/mL);28.9(Max Conc. mM)
pka	4.50±1.00(Predicted)
form	Solid
color	Light yellow to yellow

Safety information for GNE140

Signal word	Warning
Pictogram(s)	Exclamation Mark Irritant GHS07
GHS Hazard Statements	H302:Acute toxicity,oral H315:Skin corrosion/irritation H319:Serious eye damage/eye irritation H335:Specific target organ toxicity, single exposure;Respiratory tract irritation
Precautionary Statement Codes	P261:Avoid breathing dust/fume/gas/mist/vapours/spray. P305+P351+P338:IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.