1269802-97-2

Upstream product

• 6656-49-1 2-methyl-1-nitro-3-(trifluoromethyl)benzene 
• 98-80-6 phenylboronic acid 
• 259667-65-7 5-iodo-2-methyl-1-nitro-3-(trifluoromethyl)benzene 
• 1269802-85-8 methyl 3-(3-nitro-5-(trifluoromethyl)biphenyl-4-yl)-2-oxopropanoate 
• 1269802-76-7 4-methyl-3-nitro-5-(trifluoromethyl)biphenyl 

Downstream Products

• 1269802-68-7 1-hydroxy-6-phenyl-4-(trifluoromethyl)-1H-indole-2-carboxylic acid 
• 1445872-61-6 methyl 6-phenyl-1-(β-D-glucopyranosyl)oxy-4-(trifluoromethyl)-1H-indole-2-carboxylate 
• 1445872-62-7 6-phenyl-1-(β-D-2,3,4,6-tetra-O-acetylglucopyranosyl)oxy-4-(trifluoromethyl)-1H-indole-2-carboxylic acid 
• 1445873-20-0 methyl 6-phenyl-4-(trifluoromethyl)-1-(((2S,3R,4R,5R,6R)-3,4,5-trihydroxy-6-(((tetrahydro-2H-pyran-2-yl)oxy)methyl)tetrahydro-2H-pyran-2-yl)oxy)-1H-indole-2-carboxylate 
• 1445872-93-4 methyl 6-phenyl-4-(trifluoromethyl)-1-(((2S,3R,4R,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)-oxy)-1H-indole-2-carboxylate 
• 1445872-60-5 6-phenyl-1-(β-D-glucopyranosyl)oxy-4-(trifluoromethyl)-1H-indole-2-carboxylic acid 
• 1445873-19-7 methyl 1-(((2S,5R,6R)-5-hydroxy-6-(((tetrahydro-2H-pyran-2-yl)oxy)methyl)-5,6-dihydro-2H-pyran-2-yl)oxy)-6-phenyl-4-(tri-fluoromethyl)-1H-indole-2-carboxylate 
• 1445873-25-5 methyl 1-(((2R,5S,6R)-5-hydroxy-6-(((tetrahydro-2H-pyran-2-yl)oxy)methyl)-5,6-dihydro-2H-pyran-2-yl)oxy)-6-phenyl-4-(tri-fluoromethyl)-1H-indole-2-carboxylate 
• 1445872-63-8 methyl 6-phenyl-1-(β-D-2,3,4,6-tetra-O-acetylglucopyranosyl)oxy-4-(trifluoromethyl)-1H-indole-2-carboxylate 

Relevant academic research and scientific papers

Design and synthesis of novel lactate dehydrogenase a inhibitors by fragment-based lead generation

Lactate dehydrogenase A (LDHA) catalyzes the conversion of pyruvate to lactate, utilizing NADH as a cofactor. It has been identified as a potential therapeutic target in the area of cancer metabolism. In this manuscript we report our progress using fragment-based lead generation (FBLG), assisted by X-ray crystallography to develop small molecule LDHA inhibitors. Fragment hits were identified through NMR and SPR screening and optimized into lead compounds with nanomolar binding affinities via fragment linking. Also reported is their modification into cellular active compounds suitable for target validation work.

Discovery of N-hydroxyindole-based inhibitors of human lactate dehydrogenase isoform A (LDH-A) as starvation agents against cancer cells

Highly invasive tumor cells are characterized by a metabolic switch, known as the Warburg effect, from "normal" oxidative phosphorylation to increased glycolysis even under sufficiently oxygenated conditions. This dependence on glycolysis also confers a growth advantage to cells present in hypoxic regions of the tumor. One of the key enzymes involved in glycolysis, the muscle isoform of lactate dehydrogenase (LDH-A), is overexpressed by metastatic cancer cells and is linked to the vitality of tumors in hypoxia. This enzyme may be considered as a potential target for new anticancer agents, since its inhibition cuts cancer energetic and anabolic supply, thus reducing the metastatic and invasive potential of cancer cells. We have discovered new and efficient N-hydroxyindole-based inhibitors of LDH-A, which are isoform-selective (over LDH-B) and competitive with both the substrate (pyruvate) and the cofactor (NADH). The antiproliferative activity of these compounds was confirmed on a series of cancer cell lines, and they proved to be particularly effective under hypoxic conditions. Moreover, NMR experiments showed that these compounds are able to reduce the glucose-to-lactate conversion inside the cell.