IVOSIDENIB

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Search structure


Trade Names	TIBSOVO
Synonyms	AG-120 Ivosidenib Tibsovo
Status
Molecule Category	UNKNOWN
ATC	L01XX62
UNII	Q2PCN8MAM6


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

Structure


InChI Key	WIJZXSAJMHAVGX-DHLKQENFSA-N
Smiles	N#Cc1ccnc(N2C(=O)CC[C@H]2C(=O)N(c2cncc(F)c2)[C@H](C(=O)NC2CC(F)(F)C2)c2ccccc2Cl)c1
InChI	InChI=1S/C28H22ClF3N6O3/c29-21-4-2-1-3-20(21)25(26(40)36-18-11-28(31,32)12-18)37(19-10-17(30)14-34-15-19)27(41)22-5-6-24(39)38(22)23-9-16(13-33)7-8-35-23/h1-4,7-10,14-15,18,22,25H,5-6,11-12H2,(H,36,40)/t22-,25-/m0/s1

Physicochemical Descriptors

Property Name	Value
Molecular Formula	C28H22ClF3N6O3
Molecular Weight	582.97
AlogP	4.32
Hydrogen Bond Acceptor	6.0
Hydrogen Bond Donor	1.0
Number of Rotational Bond	7.0
Polar Surface Area	119.29
Molecular species	NEUTRAL
Aromatic Rings	3.0
Heavy Atoms	41.0

Bioactivity

Mechanism of Action	Action	Reference
Isocitrate dehydrogenase [NADP] cytoplasmic inhibitor	INHIBITOR	FDA


Protein: Isocitrate dehydrogenase [NADP] cytoplasmic Description: Isocitrate dehydrogenase [NADP] cytoplasmic Organism : Homo sapiens O75874 ENSG00000138413

Targets	EC50(nM)	IC50(nM)	Kd(nM)	Ki(nM)	Inhibition(%)
Enzyme Oxidoreductase	-	4-25	-	-	-

Assay Description	Organism	Bioactivity	Reference
Inhibition of IDH1 R132H mutant (unknown origin)	Homo sapiens	19.0 nM
Inhibition of IDH1 R132C mutant in human HT1080 cells assessed as reduction in 2-hydroxyglutarate production	Homo sapiens	7.5 nM
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	0.06 %
Inhibition of recombinant human C-terminal His8-tagged IDH1 R132C mutant expressed in Escherichia coli BL21 assessed as reduction in NADPH consumption using alpha-ketoglutarate as substrate preincubated for 60 mins followed by substrate addition and measured for 60 mins in presence of NADPH by diaphorase/resazurin-based fluorescence assay	Homo sapiens	23.0 nM
Inhibition of recombinant human C-terminal His8-tagged IDH1 R132H mutant expressed in Escherichia coli BL21 assessed as reduction in NADPH consumption using alpha-ketoglutarate as substrate preincubated for 60 mins followed by substrate addition measured for 60 mins in presence of NADPH by diaphorase/resazurin-based assay	Homo sapiens	3.5 nM
Inhibition of IDH1 R132C mutant in human HT1080 cells assessed as reduction in 2-HG production incubated with compound for 48 hrs by D2HG assay kit based fluorescence assay	Homo sapiens	25.4 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	2.998 %
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	0.2 %		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	0.2 %
Inhibition of IDH1 R132H mutant (unknown origin) assessed as reduction in NADPH consumption using alpha-KG as substrate incubated for 5 mins by diaphorase/resazurin-coupled system	Homo sapiens	65.0 nM
Inhibition of IDH1 R132C mutant (unknown origin) assessed as reduction in NADPH consumption using alpha-KG as substrate incubated for 5 mins by diaphorase/resazurin-coupled system	Homo sapiens	63.0 nM
Inhibition of C-terminal NanoLuc 86b-tagged IDH1 R132H (unknown origin) expressed in HEK293T cells assessed as increase in thermal stability by measuring Nano-luciferase activity at 56 degC for 3.5 min by CETSA	Homo sapiens	12.47 nM
Inhibition of IDH1 R132H mutant (unknown origin) expressed in human U87 cells assessed as R-2-hydroxyglutarate production after 48 hrs by LC-MS analysis	Homo sapiens	27.23 nM

Cross References

Resources	Reference
ChEBI	145430
ChEMBL	CHEMBL3989958
DrugBank	DB14568
DrugCentral	5292
FDA SRS	Q2PCN8MAM6
Guide to Pharmacology	9217
PubChem	71657455
SureChEMBL	SCHEMBL15122512
ZINC	ZINC000205136523

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).