1355328-30-1Relevant articles and documents
Synthesis and biological evaluation of novel PET tracers [18F]AG120 & [18F]AG135 for imaging mutant isocitrate dehydrogenase 1 expression
Cheng, Dengfeng,Cheng, Yuan,Fu, Zhequan,Lin, Qingyu,Shi, Dai,Shi, Hongcheng,Tan, Hui,Wang, Tingting,Xu, Zhan,Zhang, Yingying
, (2021/12/08)
Mutations in isocitrate dehydrogenase 1 (IDH1) are commonly found in various human malignancies. Inhibitors of several mutant IDH1 enzymes have entered clinical trials as target therapeutic drugs for the treatment of patients with IDH1 mutations. Herein, we report the synthesis and evaluation of two 18F-labeled tracers, [18F]AG120 and [18F]AG135 for imaging expression of mutated IDH1 in positron emission tomography (PET). [18F]AG120 and [18F]AG135 were synthesized in decay-corrected radiochemical yield of 1 % and 3 %, respectively, high molar activity (52–66 MBq/nmol and 216–339 MBq/nmol, respectively) and high radiochemical purity (>99%). Both tracers showed good in vitro stability, selective uptake into mutated IDH1-expressing cells and good pharmacokinetic profiles with low uptake in most organs/tissues. Furthermore, [18F]AG120 micro-PET/CT imaging displayed significantly greater uptake in IDH1-mutant than in wild-type tumors, Relatively, uptake of [18F]AG135 was observed neither in IDH1-mutant tumor xenografts nor in wild-type tumors. This study suggests that [18F]AG120 is a promising radiotracer for PET imaging of IDH1 mutation, However, further optimization and investigation are necessary for [18F]AG135 due to the limited uptake in mutated IDH1-expressing tumors.
AN IMPROVED PROCESS OF PREPARATION OF IVOSIDENIB
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Page/Page column 17, (2021/02/19)
The present invention relates to an improved process of preparation of Ivosidenib a compound of Formula (I). More particularly, present invention provides process of preparation of intermediates. Also provide process of preparation of amorphous form of Ivosidenib. Further, present invention provides process of preparation of chirally pure Ivosidenib a compound of Formula (I).
SARS-COV-2 INHIBITORS HAVING COVALENT MODIFICATIONS FOR TREATING CORONAVIRUS INFECTIONS
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Paragraph 00557-00560, (2021/11/06)
Provided herein are compounds, pharmaceutical compositions and methods for treating a SARS-CoV-2 infection.
SOLID STATE FORMS OF IVOSIDENIB
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Paragraph 00188, (2019/06/11)
Solid state forms of Ivosidenib, processes for preparation thereof, pharmaceutical compositions thereof, and uses thereof are disclosed.
Discovery of AG-120 (Ivosidenib): A First-in-Class Mutant IDH1 Inhibitor for the Treatment of IDH1 Mutant Cancers
Popovici-Muller, Janeta,Lemieux, René M.,Artin, Erin,Saunders, Jeffrey O.,Salituro, Francesco G.,Travins, Jeremy,Cianchetta, Giovanni,Cai, Zhenwei,Zhou, Ding,Cui, Dawei,Chen, Ping,Straley, Kimberly,Tobin, Erica,Wang, Fang,David, Muriel D.,Penard-Lacronique, Virginie,Quivoron, Cyril,Saada, Véronique,De Botton, Stéphane,Gross, Stefan,Dang, Lenny,Yang, Hua,Utley, Luke,Chen, Yue,Kim, Hyeryun,Jin, Shengfang,Gu, Zhiwei,Yao, Gui,Luo, Zhiyong,Lv, Xiaobing,Fang, Cheng,Yan, Liping,Olaharski, Andrew,Silverman, Lee,Biller, Scott,Su, Shin-San M.,Yen, Katharine
supporting information, p. 300 - 305 (2018/04/20)
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.
Discovery and structure-activity-relationship study of novel conformationally restricted indane analogues for mutant isocitric dehydrogenase 1 (IDH1) inhibitors
Zheng, Qiangang,Tang, Shuai,Fu, Xianlei,Chen, Ziqi,Ye, Yan,Lan, Xiaojing,Jiang, Lei,Huang, Ying,Ding, Jian,Geng, Meiyu,Huang, Min,Wan, Huixin
supporting information, p. 5262 - 5266 (2017/10/30)
The discovery and optimization of various of indane amides as mutant IDH1 inhibitors via structure-based rational design were reported. The optimal compounds demonstrated both potent inhibition in IDH1R132H enzymatic activity and 2HG production in IDH1 mutant HT1080 cell line, favorable PK properties and great selectivity against IDH1wt and IDH2R140Q.
THERAPEUTICALLY ACTIVE COMPOUNDS AND USE THEREOF
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Page/Page column 62; 63, (2015/02/19)
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
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Page/Page column 61-62, (2015/02/19)
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.
THERAPEUTICALLY ACTIVE COMPOUNDS AND THEIR METHODS OF USE
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, (2015/02/19)
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.
THERAPEUTICALLY ACTIVE COMPOUNDS AND THEIR METHODS OF USE
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, (2015/03/31)
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.