Purity: > 98%
Nitisinone(cas# 104206-65-7), also known as SC0735, is a reversible inhibitor of 4-hydroxyphenylpyruvate dioxygenase, an enzyme involved in the catabolism of tyrosine in mammals and the biosynthesis of plastoquinone in plants.
Nitisinone has been evaluated as a herbicide, while also used in the treatment of hereditary tyrosinemia type 1, alkaptonuria, and oculocutaneous albinism, all of which involve a disorder in tyrosine metabolism.
1. Orphanet J Rare Dis. 2017 Sep 11;12(1):154. doi: 10.1186/s13023-017-0696-z.
Evaluation of pre-symptomatic nitisinone treatment on long-term outcomes in
Tyrosinemia type 1 patients: a systematic review.
Geppert J(1), Stinton C(1), Freeman K(1), Fraser H(1), Clarke A(1), Johnson S(2),
Sutcliffe P(1), Taylor-Phillips S(3).
(1)Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK.
(2)Warwick Library, University of Warwick, Coventry, CV4 7AL, UK.
(3)Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK.
BACKGROUND: Tyrosinemia type 1 (TYR1) is a rare autosomal recessive disorder of
amino acid metabolism that is fatal without treatment. With medication
(nitisinone) and dietary restrictions outcomes are improved. We conducted a
systematic review to investigate if treatment with nitisinone following screening
provides better long-term outcomes than treatment with nitisinone following
METHODS: We searched Web of Science, Medline, Pre-Medline, and Embase up to 23rd
September 2016 for journal articles comparing clinical outcomes of TYR1 patients
receiving earlier versus later nitisinone treatment. Two reviewers independently
screened titles and abstracts, assessed full texts, and appraised study quality.
Data extraction was performed by a single reviewer and checked by a second.
RESULTS: We included seven articles out of 470 unique records identified by our
search. The seven articles included four studies (three cohort studies and one
cross-sectional study). Study sample sizes ranged from 17 to 148. There is
consistent evidence that nitisinone is an effective treatment for TYR1, and some
evidence that earlier treatment with nitisinone and dietary restrictions within
the first one or 2 months of life is associated with reduced need for liver
transplantation, lower rates of renal dysfunction, fewer neurological crises, and
fewer, shorter hospital admissions compared to later treatment. However, study
quality was moderate to weak, with high risk of confounding and applicability
concerns to the screening context. We conducted post hoc analyses to address
these issues. Results suggested an association between earlier treatment and
fewer liver transplants (earlier treatment: 0% of 10-24 patients; later
treatment: 25-60% of 4-15 patients), but no impact on neurological crises. We
found no effect of treatment timing on mortality in either the primary or post
hoc analyses. Post hoc analyses of other health-related outcomes were not
possible because of sample size or reporting.
CONCLUSIONS: There is some evidence from observational studies that earlier
treatment with nitisinone might be beneficial but this is subject to bias. The
applicability of our findings to the screening context or clinical practice is
limited as not all early-treated patients were identified by screening and
late-treated groups included patients born prior to the availability of
2. Appl Clin Genet. 2017 Jul 24;10:43-48. doi: 10.2147/TACG.S113310. eCollection
Clinical utility of nitisinone for the treatment of hereditary tyrosinemia type-1
(1)Department of Pediatrics, Hannover Medical School, Hannover, Germany.
Medical therapy for hereditary hepatorenal tyrosinemia (hereditary tyrosinemia
type 1, HT-1) with nitisinone was discovered incidentally, and is a by-product of
agrochemistry. It blocks the catabolic pathway of tyrosine, thereby leading to a
reduction in the accumulation of toxic metabolites in HT-1. It has to be combined
with a low-protein diet supplemented with amino acid mixtures devoid of tyrosine
and phenylalanine. This treatment option has completely changed the clinical
course of patients suffering from HT-1 who used to die in the first few months to
years of life from liver failure, renal dysfunction, and/or hepatocellular
carcinoma (HCC). It is essential to start nitisinone therapy early in life to
avoid sequelae; beginning treatment in the newborn period is ideal. As initial
clinical symptoms of HT-1 are often atypical and because there is a clinically
latent phase during the first few months of life in many patients, newborn
screening is required to secure early diagnosis. Succinylacetone in blood is a
reliable screening parameter whereas tyrosine is neither specific nor sensitive.
Especially HCC, but also liver and kidney dysfunction, rickets, and neurological
crises can be prevented in most patients if nitisinone therapy is started in the
newborn period. It is essential to adhere to a low-protein diet to avoid tyrosine
toxicity. Reversible eye symptoms may occur as a side-effect of nitisinone, but
other side effects are rare. Neurocognitive development is impaired in some
patients, and the reason for this is unclear. Metabolic monitoring includes
measurement of tyrosine, succinylacetone, and nitisinone concentrations in blood.
3. Expert Opin Pharmacother. 2008 May;9(7):1229-36. doi: 10.1517/146565126.96.36.1999.
Experience of nitisinone for the pharmacological treatment of hereditary
tyrosinaemia type 1.
Santra S(1), Baumann U.
(1)Birmingham Children/'s Hospital, The Liver Unit, Steelhouse Lane, Birmingham,
B4 6NH, UK.
BACKGROUND: Hereditary tyrosinaemia type 1 is a rare inherited metabolic
condition, which leads to a fatal multisystemic disease in childhood. Since 1992,
nitisinone - a compound developed from work on triketone herbicides - has become
an effective pharmacological treatment by inhibiting the enzyme
OBJECTIVES: This review examines recent pharmacological and clinical literature
on nitisinone, and assesses its impact as a pharmacological treatment for
hereditary tyrosinaemia type 1.
METHODS: English language literature from MedLine and EmBase for nitisinone was
searched from 1990 to 2008 for all papers relevant to the use of nitisinone in
hereditary tyrosinaemia type 1.
CONCLUSIONS: Nitisinone can prevent the development of liver disease and
significantly reduce the risk of developing hepatocellular carcinoma; however,
vigorous surveillance for the development of HCC needs to be continued lifelong.