ENASIDENIB

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Search structure


Synonyms	AG-221 Ag 221 CC-90007 Free Base Enasidenib
Status
Molecule Category	Free-form
ATC	L01XX59
UNII	3T1SS4E7AG


Active Pharmaceutical Ingredients Bioactive chemicals	Exact Similarity SubStructure	Threshold (%) >= 70

Structure


InChI Key	DYLUUSLLRIQKOE-UHFFFAOYSA-N
Smiles	CC(C)(O)CNc1nc(Nc2ccnc(C(F)(F)F)c2)nc(-c2cccc(C(F)(F)F)n2)n1
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)

Physicochemical Descriptors

Property Name	Value
Molecular Formula	C19H17F6N7O
Molecular Weight	473.38
AlogP	4.29
Hydrogen Bond Acceptor	8.0
Hydrogen Bond Donor	3.0
Number of Rotational Bond	6.0
Polar Surface Area	108.74
Molecular species	NEUTRAL
Aromatic Rings	3.0
Heavy Atoms	33.0

Assay Description	Organism	Bioactivity	Reference
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells at 10 uM after 48 hours by high content imaging	Homo sapiens	15.59 %
Inhibition of IDH2 R132Q mutant (unknown origin)	Homo sapiens	4.0 nM
Inhibition of wild type IDH2 (unknown origin)	Homo sapiens	340.0 nM
Inhibition of IDH2 R140Q mutant (unknown origin) using alpha-KG as substrate after 60 mins in presence of NADPH by resazurin-based assay	Homo sapiens	362.0 nM
In-vivo inhibition of IDH2 R140Q mutant in acute myeloid leukemia patient assessed as reduction in 2-HG levels during phase I clinical trial	Homo sapiens	90.0 %
Inhibition of IDH2 R140Q mutant (unknown origin) assessed as reduction in NADPH consumption using alpha-KG as substrate incubated for 60 mins by by diaphorase and resazurin dye based assay	Homo sapiens	262.0 nM
Inhibition of full length C-terminal His8 tagged IDH1 R132H mutant (1 to 414 residues) (unknown origin) expressed in Escherichia coli BE3 cells/wild type IDH1 (unknown origin) heterodimer assessed as reduction in NADPH consumption using alpha-ketoglutarate as substrate after 60 mins by Diaphorase/Resazurin dye based fluorescence assay	Homo sapiens	677.0 nM
Inhibition of full-length C-terminal His6 tagged IDH2 R140Q mutant (1 to 452 residues) (unknown origin) homodimer expressed in Sf9 cells assessed as reduction in NADPH consumption using alpha-ketoglutarate as substrate preincubated for 16 hrs followed by substrate addition and measured after 1 hr by Diaphorase/Resazurin dye based fluorescence assay	Homo sapiens	9.0 nM
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate	Severe acute respiratory syndrome coronavirus 2	20.11 %
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging	Chlorocebus sabaeus	0.46 %		Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging	Chlorocebus sabaeus	0.46 %
Inhibition of IDH2 R140Q mutant (unknown origin)	Homo sapiens	310.0 nM
Inhibition of IDH2 R140Q mutant (unknown origin) assessed as reduction in NADPH consumption using alpha-ketoglutarate and NADPH as substrate preincubated with enzyme for 15 mins followed by substrate addition by fluorescence based assay	Homo sapiens	35.9 nM
Inhibition of IDH2 R172K mutant (unknown origin) assessed as reduction in NADPH consumption using alpha-ketoglutarate and NADPH as substrate preincubated with enzyme for 15 mins followed by substrate addition by fluorescence based assay	Homo sapiens	269.1 nM
Inhibition of human IDH2 R140Q mutant expressed in TF-1 cells assessed as inhibition of 2-HG production at 0.1 uM incubated for 48 hrs by LC-MS/MS analysis	Homo sapiens	57.2 %
Inhibition of human IDH2 R140Q mutant expressed in TF-1 cells assessed as inhibition of 2-HG production at 10 uM incubated for 48 hrs by LC-MS/MS analysis	Homo sapiens	10.8 %

Cross References

Resources	Reference
ChEBI	145374
ChEMBL	CHEMBL3989908
DrugBank	DB13874
DrugCentral	5251
FDA SRS	3T1SS4E7AG
Guide to Pharmacology	8960
PDB	69Q
PubChem	89683805
SureChEMBL	SCHEMBL15102202
ZINC	ZINC000222731806

CONTENTS

PREMIER has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 875508. The JU receives support from the EU’s Horizon 2020 research and innovation programme and the European Federation of Pharmaceutical Industries and Associations (EFPIA). The views reflect only the authors’ perspective and the JU is not responsible for any use that may be made of the information this manuscript contains.

Elements of the website have been developed under projects PREMIER and the Biocenter Finland Drug Discovery and Chemical Biology network. CSC-IT is thanked for providing computational resources. Content of the website is provided without guarantee for correctness. Data has been collected and integrated from multiple public sources, for the largest: FDA, HUGO Gene Nomenclature Committee, ChEMBL, IUPHAR/BPS guide to pharmacology, Reactome, UniProt, and Ensembl. Credit is given to Ensembl for collecting species images (provided under public domain licences such as Wikimedia and NHGRI).