GNE-140
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Based on 1 publication(s) in Google Scholar
GNE-140 is a racemic mixture of (R)-GNE-140 (HY-100742A) and (S)-GNE-140 (HY-100742B), and it is also the racemate known as GNE-140 racemate (HY-100742). GNE-140 is an LDH inhibitor with IC50 values of 0.003 μM and 0.005 μM against LDHA and LDHB/LDHC, respectively, and also inhibits recombinant human LDH5. GNE-140 reduces lactate production in MIA PaCa-2 cells, inhibits cell proliferation, decreases glucose uptake, and elevates ROS levels, reprogramming cellular metabolic flux toward glycolysis and the pentose phosphate pathway. GNE-140 induces acquired resistance mediated by the AMPK-S6K pathway. GNE-140 inhibits the proliferation of breast cancer cells such as MDA-MB-231, inhibits LDH activity and lactate production in eye organoids, and interferes with early embryonic development in mice. GNE-140 combined with arabinoxylan attenuates intestinal inflammatory injury and improves gut microbiota diversity in choline-fed mice. GNE-140 can be used in research related to cancers such as breast cancer, ocular organ development, embryogenesis, and intestinal inflammatory diseases.
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- CAS 番号: 1809794-70-4
- 分子式: C25H23ClN2O3S2
- 分子量:499.04
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保管条件:Powder -20°C, 3 years ; In solvent -80°C, 6 months , -20°C, 1 month
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MedChemExpress（MCE）の使用を引用している文献 GNE-140
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生物活性
製品説明
GNE-140 is a racemic mixture of (R)-GNE-140 (HY-100742A) and (S)-GNE-140 (HY-100742B), and it is also the racemate known as GNE-140 racemate (HY-100742). GNE-140 is an LDH inhibitor with IC50 values of 0.003 μM and 0.005 μM against LDHA and LDHB/LDHC, respectively, and also inhibits recombinant human LDH5. GNE-140 reduces lactate production in MIA PaCa-2 cells, inhibits cell proliferation, decreases glucose uptake, and elevates ROS levels, reprogramming cellular metabolic flux toward glycolysis and the pentose phosphate pathway. GNE-140 induces acquired resistance mediated by the AMPK-S6K pathway. GNE-140 inhibits the proliferation of breast cancer cells such as MDA-MB-231, inhibits LDH activity and lactate production in eye organoids, and interferes with early embryonic development in mice. GNE-140 combined with arabinoxylan attenuates intestinal inflammatory injury and improves gut microbiota diversity in choline-fed mice. GNE-140 can be used in research related to cancers such as breast cancer, ocular organ development, embryogenesis, and intestinal inflammatory diseases[1][2][3][4][5][6].
IC50 & Target
[3]|
LDHA 3 nM (IC50) |
LDHB 5 nM (IC50) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| MIA PaCa-2 | IC50 |
0.67 μM
|
Inhibition of lactate production in human MIA PaCa-2 pancreatic cancer cells after 6 hrs exposure.
Inhibition of lactate production in human MIA PaCa-2 pancreatic cancer cells after 6 hrs exposure.
|
27479743 |
| MIA PaCa-2 | IC50 |
0.43 μM
|
Antiproliferative activity against human MIA PaCa-2 pancreatic cancer cells after 6 hrs exposure.
Antiproliferative activity against human MIA PaCa-2 pancreatic cancer cells after 6 hrs exposure.
|
27479743 |
| MIA PaCa-2 | IC50 |
0.47 μM
|
Inhibition of 18FDG-glucose uptake in human MIA PaCa-2 pancreatic cancer cells after 6 hrs exposure with 2.5 μCi FDG added for 60 mins.
Inhibition of 18FDG-glucose uptake in human MIA PaCa-2 pancreatic cancer cells after 6 hrs exposure with 2.5 μCi FDG added for 60 mins.
|
27479743 |
| MCF7 | CC50 |
64 μM
|
Acute toxicity against human MCF-7 cells assessed as CC50 greater than 64 μM after 24 hrs by resazurin assay.
Acute toxicity against human MCF-7 cells assessed as CC50 greater than 64 μM after 24 hrs by resazurin assay.
|
36436181 |
| MDA-MB-468 | CC50 |
64 μM
|
Acute toxicity against human MDA-MB-468 cells assessed as CC50 greater than 64 μM after 24 hrs by resazurin assay.
Acute toxicity against human MDA-MB-468 cells assessed as CC50 greater than 64 μM after 24 hrs by resazurin assay.
|
36436181 |
| MDA-MB-231 | CC50 |
64 μM
|
Acute toxicity against human MDA-MB-231 cells assessed as CC50 greater than 64 μM after 24 hrs by resazurin assay.
Acute toxicity against human MDA-MB-231 cells assessed as CC50 greater than 64 μM after 24 hrs by resazurin assay.
|
36436181 |
| MM96L | CC50 |
64 μM
|
Acute toxicity against human MM96L cells assessed as CC50 greater than 64 μM after 24 hrs by resazurin assay.
Acute toxicity against human MM96L cells assessed as CC50 greater than 64 μM after 24 hrs by resazurin assay.
|
36436181 |
| MDA-MB-435S | CC50 |
64 μM
|
Acute toxicity against human MDA-MB-435S cells assessed as CC50 greater than 64 μM after 24 hrs by resazurin assay.
Acute toxicity against human MDA-MB-435S cells assessed as CC50 greater than 64 μM after 24 hrs by resazurin assay.
|
36436181 |
| HT-144 | CC50 |
64 μM
|
Acute toxicity against human HT144 cells assessed as CC50 greater than 64 μM after 24 hrs by resazurin assay.
Acute toxicity against human HT144 cells assessed as CC50 greater than 64 μM after 24 hrs by resazurin assay.
|
36436181 |
| PC-3 | CC50 |
64 μM
|
Acute toxicity against human PC3 cells assessed as CC50 greater than 64 μM after 24 hrs by resazurin assay.
Acute toxicity against human PC3 cells assessed as CC50 greater than 64 μM after 24 hrs by resazurin assay.
|
36436181 |
| LNCaP | CC50 |
64 μM
|
Acute toxicity against human LnCap cells assessed as CC50 greater than 64 μM after 24 hrs by resazurin assay.
Acute toxicity against human LnCap cells assessed as CC50 greater than 64 μM after 24 hrs by resazurin assay.
|
36436181 |
| MCF-10A | CC50 |
64 μM
|
Acute toxicity against human MCF-10A cells assessed as CC50 greater than 64 μM after 24 hrs by resazurin assay.
Acute toxicity against human MCF-10A cells assessed as CC50 greater than 64 μM after 24 hrs by resazurin assay.
|
36436181 |
| MDA-MB-231 | CC50 |
16.6 μM
|
Antiproliferative activity against human MDA-MB-231 cells assessed as CC50 after 72 hrs by resazurin assay.
Antiproliferative activity against human MDA-MB-231 cells assessed as CC50 after 72 hrs by resazurin assay.
|
36436181 |
| HT-144 | CC50 |
31.8 μM
|
Antiproliferative activity against human HT144 cells assessed as CC50 after 72 hrs by resazurin assay.
Antiproliferative activity against human HT144 cells assessed as CC50 after 72 hrs by resazurin assay.
|
36436181 |
| LNCaP | CC50 |
31.7 μM
|
Antiproliferative activity against human LnCap cells assessed as CC50 after 72 hrs by resazurin assay.
Antiproliferative activity against human LnCap cells assessed as CC50 after 72 hrs by resazurin assay.
|
36436181 |
| MCF-10A | CC50 |
54.9 μM
|
Antiproliferative activity against non-cancerous human breast epithelial MCF-10A cells assessed as CC50 after 72 hrs by resazurin assay.
Antiproliferative activity against non-cancerous human breast epithelial MCF-10A cells assessed as CC50 after 72 hrs by resazurin assay.
|
36436181 |
| MDA-MB-231 | CC50 |
32 μM
|
Acute toxicity against human MDA-MB-231 cells cultured under low glucose conditions assessed as CC50 greater than 32 μM after 24 hrs by resazurin assay.
Acute toxicity against human MDA-MB-231 cells cultured under low glucose conditions assessed as CC50 greater than 32 μM after 24 hrs by resazurin assay.
|
36436181 |
| MDA-MB-231 | CC50 |
25.6 μM
|
Antiproliferative activity against human MDA-MB-231 cells cultured under low glucose conditions assessed as CC50 after 72 hrs by resazurin assay.
Antiproliferative activity against human MDA-MB-231 cells cultured under low glucose conditions assessed as CC50 after 72 hrs by resazurin assay.
|
36436181 |
| MDA-MB-231 | CC50 |
8.2 μM
|
Antiproliferative activity against human MDA-MB-231 cells cultured under low oxygen conditions assessed as CC50 after 72 hrs by resazurin assay.
Antiproliferative activity against human MDA-MB-231 cells cultured under low oxygen conditions assessed as CC50 after 72 hrs by resazurin assay.
|
36436181 |
| MDA-MB-231 | CC50 |
17.2 μM
|
Antiproliferative activity against human MDA-MB-231 cells cultured under control conditions assessed as CC50 after 72 hrs by resazurin assay.
Antiproliferative activity against human MDA-MB-231 cells cultured under control conditions assessed as CC50 after 72 hrs by resazurin assay.
|
36436181 |
| MCF7 | CC50 |
42.3 μM
|
Antiproliferative activity against human MCF-7 cells cultured under low oxygen conditions assessed as CC50 after 72 hrs by resazurin assay.
Antiproliferative activity against human MCF-7 cells cultured under low oxygen conditions assessed as CC50 after 72 hrs by resazurin assay.
|
36436181 |
体外実験
Anti-cancerCarbohydrate MetabolismMitochondrial FunctionNucleotide MetabolismOxidative StressOthers
Anti-cancer
GNE-140 inhibits breast cancer cell proliferation, and hypoxia enhances its antiproliferative effect on MDA-MB-231 and MCF-7 cells[4].
GNE‑140 can elevate ROS levels in MDA‑MB‑231 cells; it can promote a shift in cell metabolism from glycolysis to mitochondrial oxidative metabolism[4].
GNE-140 inhibits intracellular LDH activity in breast cancer cells, reduces extracellular lactate, produces a delayed inhibitory effect on proliferation, and blocks tumor cell migration and invasion; it also inhibits the proliferation of normal mammary epithelial cells and downregulates total p38 MAPK protein and blocks EGF-induced phosphorylation of p38 MAPK and AKT, but does not regulate the phosphorylation levels of ERK1/2, Src, or NF-κB[7].
GNE‑140 can elevate ROS levels in MDA‑MB‑231 cells; it can promote a shift in cell metabolism from glycolysis to mitochondrial oxidative metabolism[4].
GNE-140 inhibits intracellular LDH activity in breast cancer cells, reduces extracellular lactate, produces a delayed inhibitory effect on proliferation, and blocks tumor cell migration and invasion; it also inhibits the proliferation of normal mammary epithelial cells and downregulates total p38 MAPK protein and blocks EGF-induced phosphorylation of p38 MAPK and AKT, but does not regulate the phosphorylation levels of ERK1/2, Src, or NF-κB[7].
Anti-cancer
Carbohydrate Metabolism
GNE-140 (6 h) reduces lactate levels in MIA PaCa-2 (IC50 0.67 μM) and inhibits proliferation (IC50 0.43 μM)[2].
Carbohydrate Metabolism
GNE-140 (20 µM; 3 days) inhibits LDH activity in eye organoids, suppresses lactate production, causes arrest of optic vesicle morphogenesis, and downregulates the expression of key eye development transcription factors such as Rax, Six3, Lhx2, and Pax6[1].
GNE-140 causes a global metabolic shift in MIA PaCa-2 cells from lactate production toward glycolysis and the pentose phosphate pathway, without increasing OXPHOS[2].
GNE-140 selectively inhibits approximately 13% of pancreatic cell lines at IC50 < 5 μM, corresponding to glycolysis dependence[2].
GNE-140 induces stable >100-fold resistance in MIA PaCa-2 cells without accompanying LDHA/LDHB upregulation; combination with phenformin or S6K inhibitors restores drug sensitivity, produces a synthetic lethal effect, and prevents the emergence of resistance[2].
GNE-140 acquired resistance depends on AMPK-S6K signaling and can be prevented or resensitized by inhibiting S6K or OXPHOS in MIA PaCa-2, PSN1, and HUP T3 cells[2].
GNE-140 inhibits recombinant human LDH5 enzyme activity with an IC50 of 5.0 µM[4].
GNE-140 (7.5 μmol/L) reduces the developmental rate of mouse early embryos to the 4-cell stage, suggesting that inhibition of LDH-related metabolism impairs the ZGA process[5].
GNE-140 causes a global metabolic shift in MIA PaCa-2 cells from lactate production toward glycolysis and the pentose phosphate pathway, without increasing OXPHOS[2].
GNE-140 selectively inhibits approximately 13% of pancreatic cell lines at IC50 < 5 μM, corresponding to glycolysis dependence[2].
GNE-140 induces stable >100-fold resistance in MIA PaCa-2 cells without accompanying LDHA/LDHB upregulation; combination with phenformin or S6K inhibitors restores drug sensitivity, produces a synthetic lethal effect, and prevents the emergence of resistance[2].
GNE-140 acquired resistance depends on AMPK-S6K signaling and can be prevented or resensitized by inhibiting S6K or OXPHOS in MIA PaCa-2, PSN1, and HUP T3 cells[2].
GNE-140 inhibits recombinant human LDH5 enzyme activity with an IC50 of 5.0 µM[4].
GNE-140 (7.5 μmol/L) reduces the developmental rate of mouse early embryos to the 4-cell stage, suggesting that inhibition of LDH-related metabolism impairs the ZGA process[5].
Carbohydrate Metabolism
Mitochondrial Function
GNE-140 (20 µM) reduces glycolytic ECAR in eye organoids without affecting OCR[1].
Carbohydrate Metabolism
Nucleotide Metabolism
GNE-140 (20 µM) significantly reduces the production of 13C-labeled lactate in eye organoids, and exogenous lactate rescues the sensitive transcriptional program and the loss of H3K27ac specific to eye development gene loci in eye organoids[1].
Oxidative Stress
Carbohydrate Metabolism
GNE-140 reduces glucose uptake in MIA PaCa-2 cells (IC50 0.47 μM) and increases ROS, although ROS is not the main driver of cell death[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Viability Assay[7]
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Cell Line:pII ER- breast cancer cells, \tYS1.2 ER+ breast cancer cells
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Concentration:0.01, 0.1, 1, 10, 20, 50, 100, 200, 300 μM (4-day incubation)
200, 300 μM (1-day incubation) -
Incubation Time:4 days (for 0.01-300 μM); 1 day (for 200-300 μM)
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Result:Inhibited pII cell viability on day 4 at concentrations of 200 μM and 300 μM.
\tInhibited YS1.2 cell viability on day 4 at concentrations of 100 μM, 200 μM, and 300 μM.
Cell Migration Assay [7]
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Cell Line:pII ER- breast cancer cells, YS1.2 ER+ breast cancer cells
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Concentration:200, 300 μM
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Incubation Time:0, 24 h
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Result:Inhibited pII cell motility, as measured by reduced scratch closure, compared to untreated controls.
Inhibited YS1.2 cell motility, as measured by reduced scratch closure, compared to untreated controls.
Western Blot Analysis[7]
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Cell Line:pII ER- breast cancer cells
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Concentration:200 μM
EGF (100 ng/ml) -
Incubation Time:30 min pre-incubation prior to 30 min EGF stimulation
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Result:Reduced EGF-induced phosphorylation of p38 MAPK and AKT compared to EGF-only treated cells.
Reduced total p38 MAPK protein levels compared to EGF-only treated cells.
Did not affect EGF-induced phosphorylation of ERK1/2, Src, or NF-κB.
体内実験
Anti-cancerCarbohydrate MetabolismInnate ImmunityCytokines & ChemokinesOxidative Stress
Anti-cancer
Carbohydrate Metabolism
Innate Immunity
Cytokines & Chemokines
Oxidative Stress
Carbohydrate Metabolism
GNE-140 (AX.L) (10 mg/mL; oral gavage; every other day; starting from week 4) in combination with Arabinoxylan reduces serum TMA in choline-fed mice, alleviates colonic cytokine elevation and mucosal damage, and increases gut microbiota diversity[6].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NCR nu/nu (female; immunocompromised; Charles River Laboratories)[2]
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Dosage:100 mg/kg; 200 mg/kg; 400 mg/kg
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Administration:PO; BID; 7 d for tumor metabolite PD analysis and 21 d for tumor growth study (online Methods states 28 d)
-
Result:Observed dose-dependent declines in tumor lactate and concurrent elevations of tumor pyruvate and glycerol-3-phosphate 1 h following twice-daily oral GNE‑140 administration at 100, 200 and 400 mg/kg, whereas these metabolite alterations vanished at 6 h post-dosing.
Detected no tumor growth suppression after 21 days of twice-daily monotherapy at the three tested doses.
Found that combining GNE‑140 with phenformin failed to produce meaningful inhibition of MIA PaCa-2 xenograft tumor growth.
Related Protocols :
- BrdU Incorporation Assay
- ROS/oxidative-stress fluorescent staining
- Somatic Cell Culture
- CFSE Dye Dilution Proliferation Assay
- Dye-dilution cell tracking and proliferation staining
- Research Protocol for Microbiome Analysis
- CCK-8/WST-8 Cell Proliferation Assay
- Protocol for Cell Cycle
- Cell Counting-Based Growth Curve Assay
- Colony Formation (Clonogenic) Assay
- Breast Cancer Modeling
- Cell Viability Determination by MTT Colorimetric Assay
- EdU Incorporation Assay (Click Chemistry-Based DNA Synthesis Measurement)
- Ki-67 Immunostaining Proliferation Assay
- PCNA Immunodetection Proliferation Assay
- Protocol for Cell Counting and Cell Density Analysis
- MTT Cell Proliferation Assay
化学情報
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CAS 番号 1809794-70-4
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性状 Solid
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分子量 499.04
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分子式 C25H23ClN2O3S2
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Color Light yellow to brown
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SMILES
O=C1NC(C2=CC=C(N3CCOCC3)C=C2)(CC(O)=C1SC4=C(Cl)C=CC=C4)C5=CSC=C5
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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Powder -20°C 3 years In solvent -80°C 6 months -20°C 1 month
Publications (1)
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純度:
99.98%
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99.98%
ee.:
99.98%
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取扱説明書 (2659 KB)
参考文献
[1]. Takata N, et al. Lactate-dependent transcriptional regulation controls mammalian eye morphogenesis. Nature communications. 2023 Jul 14;14(1):4129. [Content Brief]
[2]. Boudreau A, et al. Metabolic plasticity underpins innate and acquired resistance to LDHA inhibition. Nature chemical biology. 2016 Oct;12(10):779-86. [Content Brief]
[7]. Khajah MA, et al. The effect of lactate dehydrogenase inhibitors on proliferation, motility and invasion of breast cancer cells in vitro highlights a new role for lactate. Mol Med Rep. 2024 Jan;29(1):12. [Content Brief]
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GNE-140 関連分類
HY-118241 関連分類
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