NCI-006

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[1][2][3][4][5][6][7].

Product Specifications

CAS Number

[1964516-64-0]

UNSPSC

12352100

Target

Apoptosis; Lactate Dehydrogenase; Reactive Oxygen Species (ROS)

Related Pathways

Apoptosis; Immunology/Inflammation; Metabolic Enzyme/Protease; NF-κB

Applications

Cancer-programmed cell death

Field of Research

Cancer

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

Molecular Formula

C31H24F2N4O4S3

Molecular Weight

650.74

References & Citations

[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.|[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.|[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. |[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.