Nitisinone

Nitisinone

Clinical data
AHFS/Drugs.com	Consumer Drug Information
License data	EU EMA: Orfadin US FDA: Nitisinone
Routes of administration	Oral
ATC code	A16AX04 (WHO)
Legal status
Legal status	US: ℞-only
Pharmacokinetic data
Biological half-life	Approximately 54 h
Identifiers
IUPAC name 2-[2-nitro-4-(trifluoromethyl)benzoyl] cyclohexane-1,3-dione
CAS Number	104206-65-7 Y
PubChem CID	115355
IUPHAR/BPS	6834
DrugBank	DB00348 Y
ChemSpider	103195 Y
UNII	K5BN214699
KEGG	D05177 Y
ChEBI	CHEBI:50378 Y
ChEMBL	CHEMBL1337 Y
ECHA InfoCard	100.218.521
Chemical and physical data
Formula	C14H10F3NO5
Molar mass	329.228 g/mol
3D model (Jmol)	Interactive image
SMILES O=C(c1ccc(cc1[N+]([O-])=O)C(F)(F)F)C2C(=O)CCCC2=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 Y Key:OUBCNLGXQFSTLU-UHFFFAOYSA-N Y

Nitisinone (INN), also known as NTBC (an abbreviation of its full chemical name) is a medication used to slow the effects of hereditary tyrosinemia type 1. Since its first use for this indication in 1991, it has replaced liver transplantation as the first-line treatment for this rare condition. It is also being studied in the related condition alkaptonuria. It is marketed under the brand name Orfadin by the company Swedish Orphan Biovitrum (Sobi); it was first brought to market by Swedish Orphan International. It was originally developed as a candidate herbicide.

Nitisinone is used to treat hereditary tyrosinemia type 1, in combination with restriction of tyrosine in the diet.

Since its first use for this indication in 1991, it has replaced liver transplantation as the first-line treatment for this rare condition. I It is marketed under the brand name Orfadin.

It has been demonstrated that treatment with nitisinone can reduce urinary levels of homogentisic acid in alkaptonuria patients by 95%. A series of clinical trials run by DevelopAKUre to determine whether nitisinone is effective at treating the ochronosis suffered by patients with alkaptonuria are ongoing. If the trials are successful, DevelopAKUre will try to get nitisinone licensed for use by alkaptonuria patients.

The mechanism of action of nitisinone involves reversibile inhibition of 4-Hydroxyphenylpyruvate dioxygenase (HPPD),. This is a treatment for patients with Tyrosinemia type 1 as it prevents the formation of maleylacetoacetic acid and fumarylacetoacetic acid, which have the potential to be converted to succinyl acetone, a toxin that damages the liver and kidneys. This causes the symptoms of Tyrosinemia type 1 experienced by untreated patients.