1446502-11-9

Basic information

• Product Name: Enasidenib
• Synonyms: Enasidenib;AG-221;Enasidenib(AG-221);AG-221 (Enasidenib);AG-211;2-Methyl-1-(4-(6-(trifluoromethyl)pyridin-2-yl)-6-(2-(trifluoromethyl)pyridin-4-ylamino)-1,3,5-triazin-2-ylamino)propan-2-ol;2-Propanol, 2-methyl-1-[[4-[6-(trifluoromethyl)-2-pyridinyl]-6-[[2-(trifluoromethyl)-4-pyridinyl]amino]-1,3,5-triazin-2-yl]amino]-;Enasidenib Mesylate
• CAS NO: 1446502-11-9
• Molecular Formula: C₁₉H₁₇F₆N₇O
• Molecular Weight: 473.3749992
• Product Categories: Inhibitors
• Mol File: 1446502-11-9.mol

Chemical Properties

• Boiling Point: 581.0±60.0 °C(Predicted)
• Appearance: /
• Density: 1.477±0.06 g/cm3(Predicted)
• Storage Temp.: -20°C
• Solubility: Soluble in DMSO (up to 25 mg/ml)
• PKA: 14.70±0.29(Predicted)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months.
• CAS DataBase Reference: Enasidenib(CAS DataBase Reference)
• NIST Chemistry Reference: Enasidenib(1446502-11-9)
• EPA Substance Registry System: Enasidenib(1446502-11-9)

Safety Data

• Hazardous Substances Data: 1446502-11-9(Hazardous Substances Data)

Usage

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

Upstream product

• 1446507-40-9 2,4-dichloro-6-(6-(trifluoromethyl)pyridin-2-yl)-1,3,5-triazine 
• 1446507-68-1 4-chloro-6-(6-(trifluoromethyl)pyridin-2-yl)-N-(2-(trifluoro-methyl)-pyridin-4-yl)-1,3,5-triazin-2-amine 
• 2854-16-2 1-Amino-2-methyl-propan-2-ol 
• 368-48-9 2-(trifluoromethyl)pyridine 
• 131747-42-7 6-(trifluoromethyl)pyridine-2-carboxylic acid 
• 155377-05-2 6-(trifluoromethyl)pyridine-2-carboxylic acid methyl ester 
• 1446507-38-5 6-(6-(trifluoromethyl)pyridin-2-yl)-1,3,5-triazine-2,4-(1H,3H)-dione 
• 1446507-48-7 1-((4-chloro-6-(6-(trifluoromethyl)pyridin-2-yl)-1,3,5-triazin-2-yl)amino)-2-methylpropan-2-ol 
• 147149-98-2 2-(trifluoromethyl)pyridin-4-amine 
• 887583-52-0 6-(trifluoromethyl)pyridine-2-carbonitrile 

Relevant articles and documents

2,4,6-trisubstituted-1,3,5-s-triazine compound and preparation and application thereof

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.

Preparation method of enasidenib

The invention discloses a preparation method of enasidenib. The method comprises the following steps: 6-(6-trifluoromethyl-2-yl)-1,3,5-triazine-2,4-dione is condensed with 1-amino-2-methyl-2-propanoland 2-trifluoromethyl-4-aminopyridine in sequence to generate the target compound enasidenib (I). The preparation method is simple in process, mild in condition, safe and environment-friendly, and provides a new way for industrial production.

TABLET COMPOSITIONS

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.

COMBINATION THERAPY FOR TREATING MALIGNANCIES

Provided are methods and compositions for treating AML in patients carrying an IDH2 mutation using a combination of an inhibitor of a mutant IDH2 enzyme and an AML induction and consolidation therapy.

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

Provided are methods of preparing compounds of formula (VIII) useful for treating cancer and intermediates of formula (I)

COMBINATION THERAPY FOR TREATING MALIGNANCIES

Provided are methods and compositions for treating cancers in patients carrying an IDH2 mutation using a combination of an inhibitor of a mutant IDH2 enzyme and a DNA demethylating agent.

THERAPEUTICALLY ACTIVE COMPOUNDS AND THEIR METHODS OF USE

Provided are compounds useful for treating cancer and methods of treating cancer, for example an advanced solid tumor, such as a glioma, or angioimmunoblastic T-cell lymphoma (AITL).

THERAPEUTICALLY ACTIVE COMPOUNDS AND THEIR METHODS OF USE

Provided are crystalline forms of 2-Methyl-l-[ (4-[ 6-(trifluoromethyl) pyridin-2-yl]-6-{[2-(trifluoromethyl)pyridin-4-yl]amino}-1,3,5-triazin-2- yl)amino]propan-2-ol mesylate useful for treating cancer and methods of treating cancer, comprising administering to a subject in need thereof said compound.

CRYSTALLINE FORMS OF THERAPEUTICALLY ACTIVE COMPOUNDS AND USE THEREOF

Provided are crystalline forms of 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(COMPOUND 3), 2-methyl-1-[(4- [6-(trifluoromethyl)pyridin-2-yi]-6-{ [2-(trifluoromethyl)pyridin-4- yl]amino }-1,3,5-triazin-2-yl)amino]propan-2-ol methanesulfonate (COMPOUND 1) and use thereof.

THERAPEUTICALLY ACTIVE COMPOUNDS AND THEIR METHODS OF USE

Provided are compounds useful for treating cancer and methods of treating cancer, comprising administering to a subject in need thereof a compound described herein.