NITISINONE

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Search structure


Trade Names	NITISINONE NITYR ORFADIN
Synonyms	Nitisinone Nityr Orfadin SC-0735
Status
Molecule Category	UNKNOWN
ATC	A16AX04
UNII	K5BN214699
EPA CompTox	DTXSID9042673


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

Structure


InChI Key	OUBCNLGXQFSTLU-UHFFFAOYSA-N
Smiles	O=C1CCCC(=O)C1C(=O)c1ccc(C(F)(F)F)cc1[N+](=O)[O-]
InChI	InChI=1S/C14H10F3NO5/c15-14(16,17)7-4-5-8(9(6-7)18(22)23)13(21)12-10(19)2-1-3-11(12)20/h4-6,12H,1-3H2

Physicochemical Descriptors

Property Name	Value
Molecular Formula	C14H10F3NO5
Molecular Weight	329.23
AlogP	2.73
Hydrogen Bond Acceptor	5.0
Hydrogen Bond Donor	0.0
Number of Rotational Bond	3.0
Polar Surface Area	94.35
Molecular species	NEUTRAL
Aromatic Rings	1.0
Heavy Atoms	23.0

Bioactivity

Mechanism of Action	Action	Reference
4-hydroxyphenylpyruvate dioxygenase inhibitor	INHIBITOR	FDA


Protein: 4-hydroxyphenylpyruvate dioxygenase Description: 4-hydroxyphenylpyruvate dioxygenase Organism : Homo sapiens P32754 ENSG00000158104

Targets	EC50(nM)	IC50(nM)	Kd(nM)	Ki(nM)	Inhibition(%)
Enzyme Oxidoreductase	-	40-40	-	37	50

Assay Description	Organism	Bioactivity	Reference
Inhibition of 4-hydroxyphenylpyruvate dioxygenase of purified pig liver by enol-borate method	Sus scrofa	40.0 nM
Inhibition of purified His6-tagged recombinant human HPPD assessed as inhibition of maleylacetoacetate formation after 30 mins by UV/visible spectrophotometry	Homo sapiens	37.0 nM
Inhibition of Wistar rat liver HPPD using 4-Hydroxyphenylpyruvate as substrate assessed as reduction in oxygen consumption at 50 nM preincubated for 3 mins followed by substrate addition measured after 30 secs	Rattus norvegicus	50.0 %
Inhibition of Wistar rat liver HPPD using 4-Hydroxyphenylpyruvate as substrate assessed as reduction in oxygen consumption preincubated for 3 mins followed by substrate addition	Rattus norvegicus	40.0 nM
Inhibition of Wistar rat liver cytosol HPPD using HPP as substrate assessed as reduction in O2 consumption	Rattus norvegicus	40.0 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	24.42 %		SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate	Severe acute respiratory syndrome coronavirus 2	11.6 %
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	0.0 %		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	-0.1 %		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	0.0 %		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	-0.1 %

Cross References

Resources	Reference
ChEBI	50378
ChEMBL	CHEMBL1337
DrugBank	DB00348
DrugCentral	1944
FDA SRS	K5BN214699
Human Metabolome Database	HMDB0014492
Guide to Pharmacology	6834
KEGG	D05177
PharmGKB	PA164777037
PubChem	115355
SureChEMBL	SCHEMBL338795
ZINC	ZINC000100014475

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).