Art. -Nr.: HY-176798

NCI-006

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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.

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Reinheit: 98.73%
CAS. Nr.: 1964516-64-0
Formel: C₃₁H₂₄F₂N₄O₄S₃
Molecular Weight:650.74

Speicherung:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month

NCI-006 Chemical Structure

CAS. Nr.: 1964516-64-0

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Biologische Aktivität
- Beschreibung
- Cellular Effect
- In Vitro
- In Vivo
Chemical Information
Lösungsmittel & Löslichkeit
- In Vitro
Reinheit & Dokumentation
Verweise
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

Cellular Effect

Cell Line	Type	Value	Description	References
A673	IC₅₀	119 nM Compound: 43; NACTS-SM1440	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	[PMID: 32902275]
MIA PaCa-2	IC₅₀	257 nM Compound: 43; NACTS-SM1440	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	[PMID: 32902275]

In Vitro

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.

In Vivo

NCI-006 (0-200 mg/kg, p.o./i.v., once) reduces LDH activity at 2 h in female athymic nude mice ^[3].
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.

Animal Model:

Female athymic nude mice (20-25 g)^[3]
Dosage:

0 mg/kg, 10 mg/kg, 50 mg/kg, 100 mg/kg, 200 mg/kg
Administration:

p.o., once
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.

Animal Model:

Female athymic nude mice (20-25 g)^[3]
Dosage:

0 mg/kg, 10 mg/kg, 25 mg/kg, 50 mg/kg, 100 mg/kg
Administration:

i.v., once
Result:

Dose-dependent reduced LDH activity at 2 h, but in most cases, recovery to baseline levels by 24 h.

Animal Model:

MIA PaCa-2 tumor female athymic nude mice (20-25 g)^[3]
Dosage:

50 mg/kg
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.
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).

Animal Model:

HT29 tumor female athymic nude mice (20-25 g)^[3]
Dosage:

50 mg/kg
Administration:

i.v., once
Result:

Decreased the [13C]Lac/[13C]Pyr ratio by 74.7%.
More significantly inhibits tumor growth when combined with Metformin(HY-B0627).

Animal Model:

HCT116 (5×10⁶) xenografts nude mice (18-24 g, six-week-old female KSN/slc athymic)^[6]
Dosage:

40 mg/kg
Administration:

i.v., 3 times a week, 1 weeks
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.

Animal Model:

MKN45 xenografts nude mice (18-24 g, six-week-old female KSN/slc athymic)^[6]
Dosage:

40 mg/kg
Administration:

i.v., 2 times a week, 2 weeks
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.

Animal Model:

TC71, TC32, and EW8 xenografts female Fox Chase SCID beige mice ^[7]
Dosage:

50 mg/kg
Administration:

p.o., once or twice daily, 3 weeks
Result:

Had little change in tumor growth.

Chemical Information

CAS. Nr. 1964516-64-0
Appearance Solid
Molecular Weight 650.74
Formel C₃₁H₂₄F₂N₄O₄S₃
Color White to off-white
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
Versand

Room temperature in continental US; may vary elsewhere.

Speicherung

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Lösungsmittel & Löslichkeit

In Vitro:

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)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

1.5367 mL

7.6836 mL

15.3671 mL

5 mM

0.3073 mL

1.5367 mL

3.0734 mL

10 mM

0.1537 mL

0.7684 mL

1.5367 mL

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.

Molaritätsrechner

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Konzentration Konzentration

Volumen Volumen

Molecular Weight Molecular Weight

Verdünnungsrechner

Konzentration _{(Stammlösung)} × Volumen _{(Stammlösung)} = Konzentration _{(Ziellösung)} × Volumen _{(Ziellösung)}

Konzentration _{(Stammlösung)} Konzentration _{(Stammlösung)}

Volumen _{(Stammlösung)} Volumen _{(Stammlösung)}

Konzentration _{(Ziellösung)} Konzentration _{(Ziellösung)}

Volumen _{(Ziellösung)} Volumen _{(Ziellösung)}

Reinheit & Dokumentation

Select Batch:

Reinheit: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (287 KB)
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)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

Verweise

[1]. Nobu Oshima, et al. Abstract 6222: Comprehensive monitoring of pyruvate metabolism in cancer cells and tumors reveals vulnerability to metabolic inhibition therapy with small molecules. Cancer Res 15 June 2022; 82 (12_Supplement): 6222.

[2]. Nobu Oshima, et al. Abstract 2783: Monitoring of a novel LDH inhibitor and mitochondrial inhibitor efficacy in vivo in a glycolytic pancreatic cancer model using hyperpolarized13C MRI. Cancer Res 15 August 2020; 80 (16_Supplement): 2783.

[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]

[5]. Suchet Taori, et al. Abstract 3587: Targeting cancer metabolism: A novel approach for improved radiotherapy. Cancer Res 1 July 2019; 79 (13_Supplement): 3587.

[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]

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

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

Keywords

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NCI-006

Apoptosis Compound Library

Immunology/Inflammation Compound Library

Metabolism/Protease Compound Library

NF-κB Signaling Compound Library

Anti-Cancer Compound Library

Anti-Aging Compound Library

Glycolysis Compound Library

Orally Active Compound Library

Anti-Pancreatic Cancer Compound Library

Anti-Cancer Metabolism Compound Library

Glucose Metabolism Compound Library

Anti-Colorectal Cancer Compound Library

Metabolic Enzyme Compound Library

Highly Selective Inhibitors Library

Highly Selective Activators Library

Cell Death Library

Multi-Target Compound Library

Bioactive Compound Library Max

MCE Bioactive Compound Library

Bioactive Compound Library

Anti-Gastric Cancer Compound Library

Non-Alcoholic Fatty Liver Disease (NAFLD) Compound Library

Lactic Acid Metabolic Compound Library

High-Throughput Bioactive Compound Library

Lactylation Compound Library

Alkyne Compound Library

Biologische Aktivität

Chemical Information

Lösungsmittel & Löslichkeit

Reinheit & Dokumentation

Verweise

Help & FAQs

Complete Stock Solution Preparation Table

NCI-006

Apoptosis Compound Library

Immunology/Inflammation Compound Library

Metabolism/Protease Compound Library

NF-κB Signaling Compound Library

Anti-Cancer Compound Library

Anti-Aging Compound Library

Glycolysis Compound Library

Orally Active Compound Library

Anti-Pancreatic Cancer Compound Library

Anti-Cancer Metabolism Compound Library

Glucose Metabolism Compound Library

Anti-Colorectal Cancer Compound Library

Metabolic Enzyme Compound Library

Highly Selective Inhibitors Library

Highly Selective Activators Library

Cell Death Library

Multi-Target Compound Library

Bioactive Compound Library Max

MCE Bioactive Compound Library

Bioactive Compound Library

Anti-Gastric Cancer Compound Library

Non-Alcoholic Fatty Liver Disease (NAFLD) Compound Library

Lactic Acid Metabolic Compound Library

High-Throughput Bioactive Compound Library

Lactylation Compound Library

Alkyne Compound Library

Biologische Aktivität

Chemical Information

Lösungsmittel & Löslichkeit

Reinheit & Dokumentation

Verweise

Help & FAQs

Complete Stock Solution Preparation Table

NCI-006 Related Classifications

HY-176798 Related Classifications