1448348-42-2

Upstream product

• 1242618-54-7 benzyl (3-fluoro-5-nitrophenyl)sulfane 
• 1193388-16-7 3-fluoro-5-nitrobenzene-1-sulfonyl chloride 
• 1448348-15-9 N-(tert-butyl)-3-fluoro-5-nitrobenzenesulfonamide 
• 2265-94-3 1,3-difluoro-5-nitrobenzene 
• 1355328-31-2 1,1-difluoro-3-isocyanocyclobutane 
• 1339536-41-2 3-amino-N-(tert-butyl)-5-fluorobenzenesulfonamide 
• 89-98-5 2-chloro-benzaldehyde 
• 98-79-3 L-Pyroglutamic acid 
• 1355328-30-1 N-(3,3-difluorocyclobutyl)formamide 

Downstream Products

• 1448347-30-5 (S)-N-((S)-1-(2-Chlorophenyl)-2-(3,3-difluorocyclobutylamino)-2-oxoethyl)-1-(4-cyanopyridin-2-yl)-N-(3-fluoro-5-sulfamoylphenyl)-5-oxopyrrolidine-2-carboxamide 
• 1448348-43-3 (2S)-N-(3-(N-tert-butylsulfamoyl)-5-fluorophenyl)-N-(1-(2-chlorophenyl)-2-(3,3-difluorocyclo-butylamino)-2-oxoethyl)-1-(4-cyanopyridin-2-yl)-5-oxopyrrolidine-2-carboxamide 

Relevant academic research and scientific papers

Discovery of AG-120 (Ivosidenib): A First-in-Class Mutant IDH1 Inhibitor for the Treatment of IDH1 Mutant Cancers

Somatic point mutations at a key arginine residue (R132) within the active site of the metabolic enzyme isocitrate dehydrogenase 1 (IDH1) confer a novel gain of function in cancer cells, resulting in the production of d-2-hydroxyglutarate (2-HG), an oncometabolite. Elevated 2-HG levels are implicated in epigenetic alterations and impaired cellular differentiation. IDH1 mutations have been described in an array of hematologic malignancies and solid tumors. Here, we report the discovery of AG-120 (ivosidenib), an inhibitor of the IDH1 mutant enzyme that exhibits profound 2-HG lowering in tumor models and the ability to effect differentiation of primary patient AML samples ex vivo. Preliminary data from phase 1 clinical trials enrolling patients with cancers harboring an IDH1 mutation indicate that AG-120 has an acceptable safety profile and clinical activity.

THERAPEUTICALLY ACTIVE COMPOUNDS AND USE THEREOF

Provided are therapeutically active compounds and the use in manufacture of medicaments for treating a cancer characterized by the presence of a mutant allele of IDH1.

THERAPEUTICALLY ACTIVE COMPOUNDS AND THEIR METHODS OF USE

Provided are methods of treating a cancer characterized by the presence of a mutant allele of IDH1/2 comprising administering to a subject in need thereof a compound described here.