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Chemistry

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Also known as: 1446502-11-9, Ag-221, Ag-221 (enasidenib), Enasidenib [inn], Cc-90007 free base, Idhifa
Molecular Formula
C19H17F6N7O
Molecular Weight
473.4  g/mol
InChI Key
DYLUUSLLRIQKOE-UHFFFAOYSA-N
FDA UNII
3T1SS4E7AG

Enasidenib
Enasidenib is an orally available inhibitor of specific mutant forms of the mitochondrial enzyme isocitrate dehydrogenase type 2 (IDH2), with potential antineoplastic activity. Upon administration, enasidenib specifically inhibits various mutant forms of IDH2, including the IDH2 variants R140Q, R172S, and R172K, which inhibits the formation of 2-hydroxyglutarate (2HG). This may lead to both an induction of cellular differentiation and an inhibition of cellular proliferation in IDH2-expressing tumor cells. IDH2, an enzyme in the citric acid cycle, is mutated in a variety of cancers; it initiates and drives cancer growth by blocking differentiation and the production of the oncometabolite 2HG.
Enasidenib is an Isocitrate Dehydrogenase 2 Inhibitor. The mechanism of action of enasidenib is as an Isocitrate Dehydrogenase 2 Inhibitor.
1 2D Structure

Enasidenib

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
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
2.1.2 InChI
InChI=1S/C19H17F6N7O/c1-17(2,33)9-27-15-30-14(11-4-3-5-12(29-11)18(20,21)22)31-16(32-15)28-10-6-7-26-13(8-10)19(23,24)25/h3-8,33H,9H2,1-2H3,(H2,26,27,28,30,31,32)
2.1.3 InChI Key
DYLUUSLLRIQKOE-UHFFFAOYSA-N
2.1.4 Canonical SMILES
CC(C)(CNC1=NC(=NC(=N1)C2=NC(=CC=C2)C(F)(F)F)NC3=CC(=NC=C3)C(F)(F)F)O
2.2 Other Identifiers
2.2.1 UNII
3T1SS4E7AG
2.3 Synonyms
2.3.1 MeSH Synonyms

1. Ag-221

2. Idhifa

2.3.2 Depositor-Supplied Synonyms

1. 1446502-11-9

2. Ag-221

3. Ag-221 (enasidenib)

4. Enasidenib [inn]

5. Cc-90007 Free Base

6. Idhifa

7. Ag 221

8. 2-methyl-1-(4-(6-(trifluoromethyl)pyridin-2-yl)-6-(2-(trifluoromethyl)pyridin-4-ylamino)-1,3,5-triazin-2-ylamino)propan-2-ol

9. 3t1ss4e7ag

10. 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

11. 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

12. 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

13. 2-propanol, 2-methyl-1-((4-(6-(trifluoromethyl)-2-pyridinyl)-6-((2-(trifluoromethyl)-4-pyridinyl)amino)-1,3,5-triazin-2-yl)amino)-

14. 2-propanol, 2-methyl-1-[[4-[6-(trifluoromethyl)-2-pyridinyl]-6-[[2-(trifluoromethyl)-4-pyridinyl]amino]-1,3,5-triazin-2-yl]amino]-

15. Unii-3t1ss4e7ag

16. Enasidenibum

17. Ag221

18. 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

19. Ag-221(enasidenib)

20. Ag-221; Enasidenib

21. Enasidenib; Ag-221

22. Enasidenib [mi]

23. Enasidenib (usan/inn)

24. Enasidenib [usan:inn]

25. Enasidenib [usan]

26. Enasidenib [who-dd]

27. Gtpl8960

28. Ag 221 [who-dd]

29. Chembl3989908

30. Schembl15102202

31. Ex-a654

32. Chebi:145374

33. Dtxsid801027942

34. Hms3873d03

35. Amy38698

36. Bcp16041

37. Bdbm50503251

38. Mfcd29472245

39. Nsc788120

40. S8205

41. Akos026750439

42. Zinc222731806

43. Ccg-269476

44. Cs-5017

45. Db13874

46. Nsc-788120

47. Sb19193

48. Ncgc00479249-03

49. Ncgc00479249-05

50. Ac-31318

51. As-75164

52. Hy-18690

53. Ft-0700204

54. D10901

55. A857662

56. J-690181

57. Q27077182

58. B0084-470859

59. Ag-221; Ag 221; Ag221; Cc-90007; Cc 90007; Cc90007

60. 1802003-09-3

61. 69q

2.4 Create Date
2015-02-13
3 Chemical and Physical Properties
Molecular Weight 473.4 g/mol
Molecular Formula C19H17F6N7O
XLogP33.5
Hydrogen Bond Donor Count3
Hydrogen Bond Acceptor Count14
Rotatable Bond Count6
Exact Mass473.13987716 g/mol
Monoisotopic Mass473.13987716 g/mol
Topological Polar Surface Area109 Ų
Heavy Atom Count33
Formal Charge0
Complexity635
Isotope Atom Count0
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count1
4 Drug and Medication Information
4.1 Drug Information
1 of 1  
Drug NameIDHIFA
Active IngredientENASIDENIB MESYLATE
CompanyCELGENE CORP (Application Number: N209606. Patents: 9512107, 9732062, 9738625)

4.2 Drug Indication

Indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with an isocitrate dehydrogenase-2 (IDH2) mutation.


FDA Label


Treatment of acute myeloid leukaemia


5 Pharmacology and Biochemistry
5.1 Pharmacology

In a study involving adult patients with relapsed or refractory AML, overall response rate of 40.3% was achieved in enasidenib therapy which was associated with cellular differentiation and maturation, typically without evidence of aplasia. Enasidenib is not shown to cause QTc prolongation.


5.2 FDA Pharmacological Classification
5.2.1 Active Moiety
ENASIDENIB
5.2.2 FDA UNII
3T1SS4E7AG
5.2.3 Pharmacological Classes
Mechanisms of Action [MoA] - Isocitrate Dehydrogenase 2 Inhibitors
5.3 ATC Code

L - Antineoplastic and immunomodulating agents

L01 - Antineoplastic agents

L01X - Other antineoplastic agents

L01XX - Other antineoplastic agents

L01XX59 - Enasidenib


5.4 Absorption, Distribution and Excretion

Absorption

Following a single oral dose of 100mg enasidenib, the peak plasma concentration of 1.3 mcg/mL is reached at 4 hours after ingestion. The absolute bioavailability is aproximately 57% and the steady-state plasma levels are reached within 29 days of once-daily dosing.


Route of Elimination

Elimination of enasidenib involves 89% of fecal excretion and 11% of renal excretion. Unchanged drug accounts for 34% and 0.4% of the total drug detected in the feces and urine, respectively.


Volume of Distribution

The mean volume of distribution is 55.8L.


Clearance

Enasidenib displays a mean total body clearance (CL/F) of 0.74 L/hour.


5.5 Metabolism/Metabolites

Enasidenib undergoes N-dealkylation mediated by multiple CYP (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4) and UGT (UGT1A1, UGT1A3, UGT1A4, UGT1A9, UGT2B7, and UGT2B15) enzymes to form AGI-16903, as suggested by in vitro studies. AGI-16903 can be further metabolized by CYP1A2, CYP2C19, CYP3A4, UGT1A1, UGT1A3, and UGT1A9. The parent drug accounts for 89% of total detectable drug in the circulation, while AGI-16903 represents 10% of circulating total drug.


5.6 Biological Half-Life

Enasidenib has a terminal half-life of 137 hours.


5.7 Mechanism of Action

Enasidenib is a selective inhibitor of IDH2, a mitochondria-localized enzyme involved in diverse cellular processes, including adaptation to hypoxia, histone demethylation and DNA modification. Wild-type IDH proteins play a cruicial role in the Krebs/citric acid cycle where it catalyzes the oxidative decarboxylation of isocitrate to -ketoglutarate. In comparison, mutant forms of IDH2 enzyme mediates a neomorphic activity and catalyze reduction of -KG to the (R) enantiomer of 2-hydroxyglutarate, which is associated with DNA and histone hypermethylation, altered gene expression and blocked cellular differentiation of hematopoietic progenitor cells. Enasidenib primarily targets the mutant IDH2 variants R140Q, R172S, and R172K with higher potency than the wild type enzyme form. Inhibition of the enzyme leads to decreased levels of 2-hydroxyglutarate (2-HG) and promotion of proper differentiation and clonal proliferation of cells of the myeloid lineage.


API SUPPLIERS

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Shanghai Hope Chem

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Apicore

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Apicore

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Apicore

India
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Enasidenib

About the Company : Apicore LLC, a wholly owned subsidiary of RK Pharma Inc is a leading process R&D and API manufacturing service provider for the worldwide pharmaceutical industry. We offer a wide p...

Apicore LLC, a wholly owned subsidiary of RK Pharma Inc is a leading process R&D and API manufacturing service provider for the worldwide pharmaceutical industry. We offer a wide portfolio of services ranging from API’s for the generic industry to custom synthesis for early phase pharmaceutical research and branded products. Our USFDA approved facilities in India (Visakhapatnam, Andhra Pradesh and Vadodara, Gujarat) are both equipped with state-of-the-art analytical and research capabilities. While our worldwide network of locations seamlessly integrate with each other, each unit also independently houses a full
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Enasidenib

About the Company : Hope Chem is dedicated to manufacturing, marketing, and CMO service of Active Pharmaceutical Ingredients (APIs), Intermediates, and Specialty Chemicals since the year 2010. Current...

Hope Chem is dedicated to manufacturing, marketing, and CMO service of Active Pharmaceutical Ingredients (APIs), Intermediates, and Specialty Chemicals since the year 2010. Currently, they have exclusive partnerships with multiple, state-of-the-art and GMP-compliant manufacturers in China and abroad to service our esteemed partners for competitive, long-term & stable supplies. The main products are APIs and intermediates of antiviral drug substances and anti-inflammatory, analgesic, and non-steroidal pharmaceuticals.
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Drugs in Development

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Details:

Idhifa (enasidenib) is an isocitrate dehydrogenase-2 inhibitor, which is being evaluated in combination with venetoclax for the treatment of IDH2 gene mutated acute myeloid leukemia.


Lead Product(s): Enasidenib,Venetoclax

Therapeutic Area: Oncology Brand Name: Idhifa

Study Phase: Phase I/ Phase IIProduct Type: Other Small Molecule

Sponsor: AbbVie Inc

Deal Size: Inapplicable Upfront Cash: Inapplicable

Deal Type: Inapplicable May 02, 2024

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Details : Idhifa (enasidenib) is an isocitrate dehydrogenase-2 inhibitor, which is being evaluated in combination with venetoclax for the treatment of IDH2 gene mutated acute myeloid leukemia.

Product Name : Idhifa

Product Type : Other Small Molecule

Upfront Cash : Inapplicable

May 02, 2024

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Details:

Phase 3 IDHENTIFY study evaluating IDHIFA®(enasidenib) plus best supportive care vs conventional care regimens, which include azacitidine plus BSC, low-dose cytarabine plus BSC or intermediate-dose cytarabine plus BSC, did not meet the primary endpoint.


Lead Product(s): Enasidenib,Hydroxyurea

Therapeutic Area: Oncology Brand Name: Idhifa

Study Phase: Approved FDFProduct Type: Other Small Molecule

Sponsor: Inapplicable

Deal Size: Inapplicable Upfront Cash: Inapplicable

Deal Type: Inapplicable August 25, 2020

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Details : Phase 3 IDHENTIFY study evaluating IDHIFA®(enasidenib) plus best supportive care vs conventional care regimens, which include azacitidine plus BSC, low-dose cytarabine plus BSC or intermediate-dose cytarabine plus BSC, did not meet the primary endpoint.

Product Name : Idhifa

Product Type : Other Small Molecule

Upfront Cash : Inapplicable

August 25, 2020

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ENASIDENIB MESYLATE

Brand Name : IDHIFA

Dosage Form : TABLET;ORAL

Dosage Strength : EQ 50MG BASE

Packaging :

Approval Date : 2017-08-01

Application Number : 209606

Regulatory Info : RX

Registration Country : USA

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ENASIDENIB MESYLATE

Brand Name : IDHIFA

Dosage Form : TABLET;ORAL

Dosage Strength : EQ 100MG BASE

Packaging :

Approval Date : 2017-08-01

Application Number : 209606

Regulatory Info : RX

Registration Country : USA

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ENASIDENIB MESYLATE

Brand Name : IDHIFA

Dosage Form : TABLET;ORAL

Dosage Strength : EQ 50MG BASE

Approval Date : 2017-08-01

Application Number : 209606

RX/OTC/DISCN : RX

RLD : Yes

TE Code :

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ENASIDENIB MESYLATE

Brand Name : IDHIFA

Dosage Form : TABLET;ORAL

Dosage Strength : EQ 100MG BASE

Approval Date : 2017-08-01

Application Number : 209606

RX/OTC/DISCN : RX

RLD : Yes

TE Code :

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US Medicaid Prescriptions

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Company : Celgene/BMS

Enasidenib Mesylate

Drug Cost (USD) : 118,905,343

Year : 2023

Prescribers : 813

Prescriptions : 3608

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Company : Celgene/BMS

Enasidenib Mesylate

Drug Cost (USD) : 93,705,063

Year : 2022

Prescribers : 677

Prescriptions : 3031

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Company : Celgene/BMS

Enasidenib Mesylate

Drug Cost (USD) : 78,791,111

Year : 2021

Prescribers : 605

Prescriptions : 2646

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Company : Celgene/BMS

Enasidenib Mesylate

Drug Cost (USD) : 75,226,515

Year : 2020

Prescribers : 608

Prescriptions : 2657

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Company : Celgene

Enasidenib Mesylate

Drug Cost (USD) : 57,551,679

Year : 2019

Prescribers : 506

Prescriptions : 2121

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Company : Celgene

Enasidenib Mesylate

Drug Cost (USD) : 42,806,444

Year : 2018

Prescribers : 456

Prescriptions : 1636

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Patents & EXCLUSIVITIES

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US Patents

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ENASIDENIB MESYLATE

US Patent Number : 9512107

Drug Substance Claim : Y

Drug Product Claim : Y

Application Number : 209606

Patent Use Code : U-2087

Delist Requested :

Patent Use Description :

Patent Expiration Date : 2033-01-07

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ENASIDENIB MESYLATE

US Patent Number : 9732062

Drug Substance Claim : Y

Drug Product Claim :

Application Number : 209606

Patent Use Code :

Delist Requested :

Patent Use Description :

Patent Expiration Date : 2034-09-16

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ENASIDENIB MESYLATE

US Patent Number : 10093654

Drug Substance Claim : Y

Drug Product Claim : Y

Application Number : 209606

Patent Use Code : U-2087

Delist Requested :

Patent Use Description :

Patent Expiration Date : 2034-08-01

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ENASIDENIB MESYLATE

US Patent Number : 9738625

Drug Substance Claim : Y

Drug Product Claim :

Application Number : 209606

Patent Use Code :

Delist Requested :

Patent Use Description :

Patent Expiration Date : 2034-08-01

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ENASIDENIB MESYLATE

US Patent Number : 10093654

Drug Substance Claim : Y

Drug Product Claim : Y

Application Number : 209606

Patent Use Code : U-2087

Delist Requested :

Patent Use Description :

Patent Expiration Date : 2034-08-01

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ENASIDENIB MESYLATE

US Patent Number : 10294215

Drug Substance Claim :

Drug Product Claim : Y

Application Number : 209606

Patent Use Code : U-2087

Delist Requested :

Patent Use Description :

Patent Expiration Date : 2033-01-07

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ENASIDENIB MESYLATE

US Patent Number : 10610125

Drug Substance Claim :

Drug Product Claim :

Application Number : 209606

Patent Use Code : U-2087

Delist Requested :

Patent Use Description :

Patent Expiration Date : 2030-06-21

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ENASIDENIB MESYLATE

US Patent Number : 10610125

Drug Substance Claim :

Drug Product Claim :

Application Number : 209606

Patent Use Code : U-2087

Delist Requested :

Patent Use Description :

Patent Expiration Date : 2030-06-21

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US Patent Number : 9732062

Drug Substance Claim : Y

Drug Product Claim :

Application Number : 209606

Patent Use Code :

Delist Requested :

Patent Use Description :

Patent Expiration Date : 2034-09-16

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ENASIDENIB MESYLATE

US Patent Number : 9512107

Drug Substance Claim : Y

Drug Product Claim : Y

Application Number : 209606

Patent Use Code : U-2087

Delist Requested :

Patent Use Description :

Patent Expiration Date : 2033-01-07

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ABOUT THIS PAGE

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API | Excipient name

Enasidenib

Synonyms

1446502-11-9, Ag-221, Ag-221 (enasidenib), Enasidenib [inn], Cc-90007 free base, Idhifa

Cas Number

1802003-09-3

Unique Ingredient Identifier (UNII)

3T1SS4E7AG

About Enasidenib

Enasidenib is an orally available inhibitor of specific mutant forms of the mitochondrial enzyme isocitrate dehydrogenase type 2 (IDH2), with potential antineoplastic activity. Upon administration, enasidenib specifically inhibits various mutant forms of IDH2, including the IDH2 variants R140Q, R172S, and R172K, which inhibits the formation of 2-hydroxyglutarate (2HG). This may lead to both an induction of cellular differentiation and an inhibition of cellular proliferation in IDH2-expressing tumor cells. IDH2, an enzyme in the citric acid cycle, is mutated in a variety of cancers; it initiates and drives cancer growth by blocking differentiation and the production of the oncometabolite 2HG.

Enasidenib mesylate Manufacturers

A Enasidenib mesylate manufacturer is defined as any person or entity involved in the manufacture, preparation, processing, compounding or propagation of Enasidenib mesylate, including repackagers and relabelers. The FDA regulates Enasidenib mesylate manufacturers to ensure that their products comply with relevant laws and regulations and are safe and effective to use. Enasidenib mesylate API Manufacturers are required to adhere to Good Manufacturing Practices (GMP) to ensure that their products are consistently manufactured to meet established quality criteria.

click here to find a list of Enasidenib mesylate manufacturers with USDMF, JDMF, KDMF, CEP, GMP, COA and API Price related information on PhamaCompass.

Enasidenib mesylate Suppliers

A Enasidenib mesylate supplier is an individual or a company that provides Enasidenib mesylate active pharmaceutical ingredient (API) or Enasidenib mesylate finished formulations upon request. The Enasidenib mesylate suppliers may include Enasidenib mesylate API manufacturers, exporters, distributors and traders.

click here to find a list of Enasidenib mesylate suppliers with USDMF, JDMF, KDMF, CEP, GMP, COA and API Price related information on PharmaCompass.

Enasidenib mesylate GMP

Enasidenib mesylate Active pharmaceutical ingredient (API) is produced in GMP-certified manufacturing facility.

GMP stands for Good Manufacturing Practices, which is a system used in the pharmaceutical industry to make sure that goods are regularly produced and monitored in accordance with quality standards. The FDA’s current Good Manufacturing Practices requirements are referred to as cGMP or current GMP which indicates that the company follows the most recent GMP specifications. The World Health Organization (WHO) has its own set of GMP guidelines, called the WHO GMP. Different countries can also set their own guidelines for GMP like China (Chinese GMP) or the EU (EU GMP).

PharmaCompass offers a list of Enasidenib mesylate GMP manufacturers, exporters & distributors, which can be sorted by USDMF, JDMF, KDMF, CEP (COS), WC, API price, and more, enabling you to easily find the right Enasidenib mesylate GMP manufacturer or Enasidenib mesylate GMP API supplier for your needs.

Enasidenib mesylate CoA

A Enasidenib mesylate CoA (Certificate of Analysis) is a formal document that attests to Enasidenib mesylate's compliance with Enasidenib mesylate specifications and serves as a tool for batch-level quality control.

Enasidenib mesylate CoA mostly includes findings from lab analyses of a specific batch. For each Enasidenib mesylate CoA document that a company creates, the USFDA specifies specific requirements, such as supplier information, material identification, transportation data, evidence of conformity and signature data.

Enasidenib mesylate may be tested according to a variety of international standards, such as European Pharmacopoeia (Enasidenib mesylate EP), Enasidenib mesylate JP (Japanese Pharmacopeia) and the US Pharmacopoeia (Enasidenib mesylate USP).

Inform the supplier about your product requirements, specifying if you need a product with particular monograph like EP (Ph. Eur.), USP, JP, BP, or any other quality. In addition, clarify whether you need hydrochloride (HCl), anhydricum, base, micronisatum or a specific level of purity. To find reputable suppliers, utilize the filters and select those certified by GMP, FDA, or any other certification as per your requirement.
For your convenience, we have listed synonyms and CAS numbers to help you find the best supplier. The use of synonyms and CAS numbers can be helpful in identifying potential suppliers, but it is crucial to note that they might not always indicate the exact same product. It is important to confirm the product details with the supplier before making a purchase to ensure that it meets your requirements.
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