NCI-006
Based on 1 Customer Validation
NCI-006 is an orally active lactate dehydrogenase (LDH) inhibitor (LDHA IC50 = 0.06 μM; LDHB IC50 = 0.03 μM). NCI-006 inhibits intratumoral LDH activity, lactate production, and tumor growth in a mouse pancreatic cancer model. NCI-006 inhibits glycolysis and induces apoptosis in vitro. NCI-006 enhances the radiosensitivity of glycolytic tumor cell lines while sparing non-glycolytic/normal cells (1522, skin fibroblasts) in combination with ionizing radiation (IR). NCI-006 exhibits synergistic antitumor effects in combination with IACS-010759 (HY-112037) against colorectal and gastric cancers. NCI-006 targets glycolysis by inhibiting lactate dehydrogenase impairs tumor growth in an Ewing sarcoma model.
Para uso exclusivo en investigación. No vendemos a pacientes.
- Pureza: 98.73%
- No. CAS: 1964516-64-0
- Fòrmula: C31H24F2N4O4S3
- Peso molecular:650.74
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Almacenamiento:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Actividad biológica
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Chemical Information
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Solvente y solubilidad
- Pureza y Documentación
- Referencias
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Help & FAQs
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Apoptosis Compound Library
HY-L003
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Immunology/Inflammation Compound Library
HY-L007
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Metabolism/Protease Compound Library
HY-L012
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NF-κB Signaling Compound Library
HY-L014
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Anti-Cancer Compound Library
HY-L025
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Anti-Aging Compound Library
HY-L034
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Glycolysis Compound Library
HY-L058
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Orally Active Compound Library
HY-L061
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Anti-Pancreatic Cancer Compound Library
HY-L077
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Anti-Cancer Metabolism Compound Library
HY-L083
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Glucose Metabolism Compound Library
HY-L092
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Anti-Colorectal Cancer Compound Library
HY-L103
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Metabolic Enzyme Compound Library
HY-L146
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Highly Selective Inhibitors Library
HY-L158
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Highly Selective Activators Library
HY-L159
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Cell Death Library
HY-L162
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Multi-Target Compound Library
HY-L176
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Bioactive Compound Library Max
HY-L181
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MCE Bioactive Compound Library
HY-L001V
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Bioactive Compound Library
HY-L001
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Anti-Gastric Cancer Compound Library
HY-L184
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Non-Alcoholic Fatty Liver Disease (NAFLD) Compound Library
HY-L199
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Lactic Acid Metabolic Compound Library
HY-L204
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High-Throughput Bioactive Compound Library
HY-L205
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Lactylation Compound Library
HY-L249
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Alkyne Compound Library
HY-L258
Actividad biológica
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| A673 | IC50 |
119 nM
Compound: 43; NACTS-SM1440
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Cytotoxicity against human A673 cells assessed as reduction in cell viability after 48 hrs by CellTiter-Glo assay
Cytotoxicity against human A673 cells assessed as reduction in cell viability after 48 hrs by CellTiter-Glo assay
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[PMID: 32902275] |
| MIA PaCa-2 | IC50 |
257 nM
Compound: 43; NACTS-SM1440
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Cytotoxicity against human MIA PaCa-2 cells assessed as reduction in cell viability after 48 hrs by CellTiter-Glo assay
Cytotoxicity against human MIA PaCa-2 cells assessed as reduction in cell viability after 48 hrs by CellTiter-Glo assay
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[PMID: 32902275] |
NCI-006 (0-1 μM) inhibits the activity of human LDH (hLDH), and the HEK293T cells isoenzymes 2, 3, 4, 5 and mouse isoenzymes 1, 2, 3, 4, 5, does not inhibit the activity of malate dehydrogenase (MDH) and succinate dehydrogenase (SDH) isolated from human kidney[3].
NCI-006 (0.2-5 μM,2 h) reduces the NAD/NADH ratio in MIA PaCa-2 and HT29 cells, affects lactate secretion in mouse (m) and human (h) red blood cells (RBCs) as well as MIA PaCa-2 and HT29 cells, with EC50s of 1.6, 2.1, 0.37, 0.53 μM [3].
NCI-006(0-10 μM, 0-180 min) reduces the basal extracellular acidification rate (ECAR) in a time-dependent manner at a minimum concentration of 1 μM and inhibits glycolysis at concentrations ≥ 1 μM, and improves basic oxygen consumption rate (OCR) in MIA PaCa-2 cells[3].
NCI-006 (1 μM) combined with IACS-010759 (HY-112037) reduces cell viability in MIA PaCa-2, HCT116, and MKN45 cells[3][6].
NCI-006 (5 μM) reduces OCR, ECAR, sugar ATP production rate, has no change of mito ATP production rate or total ATP production rate, does not increase mitotic ATP production rate, but significantly increases sugar ATP production rate in combination with IACS-010759 (HY-112037) in HCT116 and MKN45 cells[6].
NCI-006 (72 h) inhibits ewing sarcoma cell lines proliferation, with IC50s ranging from 100 nmol/L (TC71 and TC32) to 1 μmol/L (RDES and EW8), has no effect of rhabdomyosarcoma and osteosarcoma, with an IC50 of 1037 nmol/L[7].
NCI-006 dose-dependently inhibits LDH activity in TC71, TC32, EW8 cells, with IC50s approximately 100 nmol/L[7].
NCI-006 (0.1-10 μM, 2 h) inhibits ECAR in TC71 and EW8 cells[7].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
NCI-006 (50 mg/kg, p.o./i.v., once; i.v., every other day for 1 week, or for 2 weeks) inhibits tumor LDH activity, resulting in decreased conversion of pyruvate to lactate, with enhanced pyruvate flux to bicarbonate and mitochondrial oxidation, without a detectable increase in transaminase-mediated pyruvate flux to alanine, slows the tumor growth in MIA PaCa-2/HT29 tumor female athymic nude mice[3].
NCI-006 (40 mg/kg, i.v., 2/3 times a week, 1/2 weeks) treatment alone does not inhibit tumor growth, inhibits tumor growth in combination with IACS-010759 (HY-112037) in HCT116 and MKN45 xenografts nude mice[6].
NCI-006 (50 mg/kg, p.o., once or twice daily, 3 weeks) has little change in tumor growth in TC71, TC32, and EW8 xenografts female Fox Chase SCID beige mice[7].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Female athymic nude mice (20-25 g)[3]
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Dosage:0 mg/kg, 10 mg/kg, 50 mg/kg, 100 mg/kg, 200 mg/kg
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Administration:p.o., once
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Result:Dose-dependent reduced LDH activity at 2 h, but in most cases, recovery to baseline levels by 24 h, 75%-80% of baseline at 24 h, with maximal inhibition maintained at 8 h.
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Animal Model:Female athymic nude mice (20-25 g)[3]
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Dosage:0 mg/kg, 10 mg/kg, 25 mg/kg, 50 mg/kg, 100 mg/kg
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Administration:i.v., once
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Result:Dose-dependent reduced LDH activity at 2 h, but in most cases, recovery to baseline levels by 24 h.
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Animal Model:MIA PaCa-2 tumor female athymic nude mice (20-25 g)[3]
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Dosage:50 mg/kg
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Administration:p.o./i.v., once; i.v., every other day for 1 week (three injections, Monday, Wednesday, and Friday), or for 2 weeks (six injections) with a break of 1 week between cycles.
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Result:Inhibited LDH by 80% at intratumoral drug levels of approximately 20 μM.
Dose dependently suppressed the tumor [13C]lactate/[13C]pyruvate ratio, did not affect the [13C]lactate/[13C]pyruvate ratio in MIA PaCa-2 tumors (up to 7 h after drug administration).
Slowed the growth of MIA PaCa-2 xenografts without a marked effect on mouse body weight.
Reduced conversion of [13C]pyruvate to both [13C]lactate and [13C]bicarbonate, more significantly inhibits tumor growth in combination with IACS-010759 (HY-112037).
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Animal Model:HT29 tumor female athymic nude mice (20-25 g)[3]
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Dosage:50 mg/kg
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Administration:i.v., once
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Result:Decreased the [13C]Lac/[13C]Pyr ratio by 74.7%.
More significantly inhibits tumor growth when combined with Metformin(HY-B0627).
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Animal Model:HCT116 (5×106) xenografts nude mice (18-24 g, six-week-old female KSN/slc athymic)[6]
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Dosage:40 mg/kg
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Administration:i.v., 3 times a week, 1 weeks
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Result:Treatment alone did not inhibit tumor growth, inhibited tumor growth and transiently and significantly increased AST, ALT, amylase, lipase, creatinine, and bilirubin levels in combination with IACS-010759 (HY-112037).
Decreased the 13C-L/P ratio, increased ROS levels.
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Animal Model:MKN45 xenografts nude mice (18-24 g, six-week-old female KSN/slc athymic)[6]
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Dosage:40 mg/kg
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Administration:i.v., 2 times a week, 2 weeks
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Result:Treatment alone did not inhibit tumor growth, inhibited tumor growth and transiently and significantly increased AST, ALT, amylase, lipase, creatinine, and bilirubin levels in combination with IACS-010759 (HY-112037).
Decreased the 13C-L/P ratio.
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Animal Model:TC71, TC32, and EW8 xenografts female Fox Chase SCID beige mice [7]
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Dosage:50 mg/kg
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Administration:p.o., once or twice daily, 3 weeks
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Result:Had little change in tumor growth.
Chemical Information
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No. CAS 1964516-64-0
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Appearance Solid
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Peso molecular 650.74
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Fòrmula C31H24F2N4O4S3
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Color White to off-white
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SMILES
O=C(C1=CSC(N2N=C(C(CC3=CC=C(S(=O)(N)=O)C(F)=C3)=C2CC4CC4)C5=CC(C#CC6=CC=C(C)S6)=C(F)C=C5)=N1)O
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvente y solubilidad
DMSO : 50 mg/mL (76.84 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Pureza y Documentación
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Ficha de datos (287 KB)
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SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Korean - KR (251 KB)
- Portuguese - PT (251 KB)
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Instrucciones de manejo (2659 KB)
Referencias
[3]. Oshima N, et al. Dynamic Imaging of LDH Inhibition in Tumors Reveals Rapid In Vivo Metabolic Rewiring and Vulnerability to Combination Therapy. Cell Rep. 2020 Feb 11;30(6):1798-1810.e4. [Content Brief]
[4]. Rai G, et al. Discovery and Optimization of Potent, Cell-Active Pyrazole-Based Inhibitors of Lactate Dehydrogenase (LDH). J Med Chem. 2017 Nov 22;60(22):9184-9204. [Content Brief]
[6]. Aisu Y, et al. Dual inhibition of oxidative phosphorylation and glycolysis exerts a synergistic antitumor effect on colorectal and gastric cancer by creating energy depletion and preventing metabolic switch. PLoS One. 2024 Dec 12;19(12):e0309700. [Content Brief]
[7]. Yeung C, et al. Targeting Glycolysis through Inhibition of Lactate Dehydrogenase Impairs Tumor Growth in Preclinical Models of Ewing Sarcoma. Cancer Res. 2019 Oct 1;79(19):5060-5073. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.5367 mL | 7.6836 mL | 15.3671 mL | 38.4178 mL |
| 5 mM | 0.3073 mL | 1.5367 mL | 3.0734 mL | 7.6836 mL | |
| 10 mM | 0.1537 mL | 0.7684 mL | 1.5367 mL | 3.8418 mL | |
| 15 mM | 0.1024 mL | 0.5122 mL | 1.0245 mL | 2.5612 mL | |
| 20 mM | 0.0768 mL | 0.3842 mL | 0.7684 mL | 1.9209 mL | |
| 25 mM | 0.0615 mL | 0.3073 mL | 0.6147 mL | 1.5367 mL | |
| 30 mM | 0.0512 mL | 0.2561 mL | 0.5122 mL | 1.2806 mL | |
| 40 mM | 0.0384 mL | 0.1921 mL | 0.3842 mL | 0.9604 mL | |
| 50 mM | 0.0307 mL | 0.1537 mL | 0.3073 mL | 0.7684 mL | |
| 60 mM | 0.0256 mL | 0.1281 mL | 0.2561 mL | 0.6403 mL |
NCI-006 Related Classifications
HY-176798 Related Classifications
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