1446502-11-9 Usage
Description
Enasidenib (1446502-11-9) is a potent (IC50’s = 100 nM IDH2R140Q homodimer, 30 nM IDH2R140Q/WT heterodimer and 10 nM IDH2R172K/WT heterodimer) and selective inhibitor of mutant isocitrate dehydrogenase 2 (IDH2).1? It suppressed the production of the oncometabolite (R)-2-Hydroxyglutarate (a competitive inhibitor of αKG-dependent dioxygenases which leads to epigenetic dysregulation) and induced cellular differentiation in primary human IDH2 mutation-positive acute myeloid leukemia cells.1,2? Recently approved for clinical use by the FDA.
Uses
Enasidenib is a first-in-class oral selective inhibitor of mutant IDH2 enzymes (isocitrate dehydrogenase 2), for the treatment of adults with relapsed or refractory IDH2-mutated acute myeloid leukemia.
in vitro
ag-221 was found to be able to reduce 2-hg levels by >90%, reverse in-vitro histone and dna hypermethylation, and induce differentiation in leukemia cell model as well. in addition, a dose dependent proliferative burst of the human specific cd45+ blast cells was observed by the treatment of ag-221, as measured by the expression of cd11b, cd14, cd15 and cell morphology [1].
in vivo
the efficacy of ag-221 in a primary human aml xenograft model with the idh2 r140q mutation was studied, and the results showed that ag-221 could reduce 2-hg in the plasma, bone marrow, and urine of engrafted mice potently. in addition, the treatment of ag-221 could also induce a significant and dose dependent survival benefit as demonstrated by that all mice in the high dose treatment of ag-221 survived to the end of study [1].
IC 50
~16 nm for idh2 r140q mutant
References
1) Yen et al. (2017), AG-221, A First-in-Class Therapy Targeting Acute Myeloid Leukemia Harboring Oncogenic IDH2 Mutations; Cancer Discov. 7 478
2) Amatangelo et al. (2017), Enasidenib induces acute myeloid leukemia cell differentiation to promote clinical response; Blood 130 732
Check Digit Verification of cas no
The CAS Registry Mumber 1446502-11-9 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,4,4,6,5,0 and 2 respectively; the second part has 2 digits, 1 and 1 respectively.
Calculate Digit Verification of CAS Registry Number 1446502-11:
(9*1)+(8*4)+(7*4)+(6*6)+(5*5)+(4*0)+(3*2)+(2*1)+(1*1)=139
139 % 10 = 9
So 1446502-11-9 is a valid CAS Registry Number.
1446502-11-9Relevant articles and documents
2,4,6-trisubstituted-1,3,5-s-triazine compound and preparation and application thereof
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, (2021/10/05)
The invention provides a 2,4,6-trisubstituted-1,3,5-s-triazine compound as well as preparation and application thereof, and biguanide or dimethyl biguanide hydrochloride is used as an initial raw material to react with a cyano compound under an alkaline condition to prepare the 2,4,6-trisubstituted-1,3,5-s-triazine compound. The invention provides a simple and convenient synthetic method of a 2,4,6-trisubstituted-1,3,5-s-triazine compound, and the compound provided by the invention can be applied to preparation of an anti-myelogenous leukemia medicine, namely an enasidenib medicine. Compared with the prior art, the method for preparing the enasidenib has the advantages that two-step reaction is reduced, the use of a halogenating reagent is avoided, and the method is a green and environment-friendly chemical process. The structural formula I is shown in the specification.
TABLET COMPOSITIONS
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, (2018/03/25)
Provided herein is a tablet comprising 2-methyl-1-[(4-[6-(trifluoromethyl)pyridin-2-yl]-6-{[2-(trifluoromethyl)pyridin-4-yl]amino}-1,3,5-triazin-2-yl)amino]propan-2-ol or a pharmaceutically acceptable salt thereof.
METHODS OF PREPARING 6-(ARYL OR HETEROARYL)-1,3,5-TRIAZINE-2,4-DIOLS AND 6-(ARYL OR HETEROARYL)-1,3,5-TRIAZINE-2,4-DIAMINES
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Paragraph 0073; 0078, (2017/02/28)
Provided are methods of preparing compounds of formula (VIII) useful for treating cancer and intermediates of formula (I)
