1446502-11-9 Usage
Description
Enasidenib, also known as AG-221, is a first-in-class, potent, and selective oral inhibitor of mutant isocitrate dehydrogenase 2 (IDH2) enzymes. It has been specifically designed to target and suppress the activity of the mutated IDH2 proteins, which are responsible for the production of the oncometabolite (R)-2-hydroxyglutarate (2-HG). This oncometabolite acts as a competitive inhibitor of αKG-dependent dioxygenases, leading to epigenetic dysregulation and contributing to the development of certain cancers. Enasidenib has demonstrated the ability to induce cellular differentiation in primary human IDH2 mutation-positive acute myeloid leukemia (AML) cells. It has been recently approved for clinical use by the FDA.
Uses
Used in Oncology:
Enasidenib is used as an anticancer agent for the treatment of adults with relapsed or refractory IDH2-mutated acute myeloid leukemia (AML). By inhibiting the mutant IDH2 enzymes, Enasidenib effectively reduces the production of the oncometabolite 2-HG, which in turn helps to restore normal cellular differentiation and potentially halt the progression of the disease. This targeted approach offers a novel therapeutic option for patients with IDH2-mutated AML, who may not respond well to traditional chemotherapy or may have relapsed after initial treatment.
In addition to its direct anticancer effects, Enasidenib may also be used in combination with other cancer treatments to enhance their efficacy and overcome resistance mechanisms. Further research and clinical trials are needed to explore the potential synergistic effects of Enasidenib when combined with other therapies in the treatment of various types of cancer.
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
-
, (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
-
, (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
-
Paragraph 0073; 0078, (2017/02/28)
Provided are methods of preparing compounds of formula (VIII) useful for treating cancer and intermediates of formula (I)