[CAS NO. 104206-65-7] Nitisinone

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PRODUCTS SPECIFICATIONS [104206-65-7]

Catalog

HY-B0607

Brand

MCE

CAS

104206-65-7

DESCRIPTION [104206-65-7]

Overview

MDL	MFCD01752192
Molecular Weight	329.23
Molecular Formula	C14H10F3NO5
SMILES	O=C1C(C(C2=CC=C(C(F)(F)F)C=C2[N+]([O-])=O)=O)C(CCC1)=O

For research use only. We do not sell to patients.

1 Publications Citing Use of MCE

[1]Int Immunopharmacol. 2022 Aug 6;111:109098.

Summary

Nitisinone is an orally active, competitive and reversible 4-hydroxyphenylpyruvate dioxygenase ( 4-HPPD ) inhibitor with an IC ₅₀ of 173 nM. Nitisinone promotes tyrosine accumulation in a dose-dependent manner. nitisinone can be used in studies of hereditary tyrosinemia type 1 (HT-1) (a rare genetic disorder) and albinism ^[1] ^[2] ^[3] ^[4] .

In Vitro

Nitisinone (0.01-10 µM; 72 h) promotes tyrosine accumulation in a dose-dependent manner ^[1] .

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Viability Assay ^[1]

Cell Line:	Human primary fibroblasts (HFb)
Concentration:	0.01-10 µM
Incubation Time:	72 h
Result:	Exhibited massive intracellular accumulation of tyrosine in human cell cultures.

In Vivo

Nitisinone (5, 10 mg/kg; p.o.; 5 days aweek for 6 weeks) inhibits HPPD in a dose- and time- dependent manner in rat liver ^[2] .
Nitisinone (4 mg/kg; p.o.; single daily; one day interval for 1 month) elevates tyrosine in both OCA-1A and OCA-1B model ^[3] .
Nitisinone (4 mg/kg; p.o.; single daily; one day interval for 1 month) increases coat and iris pigmentation and melanin content in the melanosomes of ocular tissues in a mouse model of OCA-1B ^[3] .
Note: Oculocutaneous albinism, type 1 (OCA1). There are 2 forms of OCA1, OCA-1A and OCA-1B. Individuals with the former lack functional tyrosinase and therefore lack melanin, while individuals with the latter produce some melanin ^[3] .

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	Male Wistar rats (120-150 g) ^[2] .
Dosage:	5, 10 mg/kg
Administration:	Oral gavage; 5 days aweek for 6 weeks.
Result:	Inhibited HPPD in a dose- and time- dependent manner in rat liver. (rat liver form animal model, incubate with 0-200 nM Nitisinone for 3 min).

Animal Model:	C57BL/6J mice (WT mice), Tyrc ^-2J/c-2J mice (model of OCA-1A) and Tyrc ^-h/c-h mice (model of OCA-1B) (all are 3 to 4-month-age) ^[3] .
Dosage:	4 mg/kg
Administration:	Oral gavage; single daily; every other day for 1 month.
Result:	Elevated plasma tyrosine levels 4- to 6- fold compared with placebo-treated controls, after 1 month in both OCA-1A and OCA-1B model. Increased pigmentation in the irides and pigmentation in areas of new hair growth upon physical, in OCA-1B model. Significant increased in the number of pigmented melanosomes in OCA-1B model. Showed substantial pigmentation in the irides of Tyrc ^-h/c-h pups born of Nitisinone-treated mothers.

Clinical Trial

NCT Number	Sponsor	Condition	Start Date	Phase
NCT01390077	University of California, San Diego	Alkaptonuria	January 2011	Phase 2\|Phase 3
NCT02750345	Cycle Pharmaceuticals Ltd.\|Parexel	Hereditary Tyrosinemia, Type I	March 2016	Phase 1
NCT03103568	Swedish Orphan Biovitrum\|Parexel	Drug Drug Interaction	March 28, 2017	Phase 1
NCT01916382	University of Liverpool	Alkaptonuria	April 2014	Phase 3
NCT02320084	Swedish Orphan Biovitrum	Hereditary Tyrosinemia, Type I	September 2013
NCT00004443	University of Washington\|FDA Office of Orphan Products Development	Tyrosinemia I	October 1998	Not Applicable
NCT01734889	Swedish Orphan Biovitrum	Hereditary Tyrosinemia, Type I	October 2012	Phase 1
NCT01857362	Swedish Orphan Biovitrum	Healthy	May 2013	Phase 1
NCT00031161	University of Florida\|FDA Office of Orphan Products Development	Acidosis, Lactic\|Chronic Disease	September 2001	Not Applicable
NCT02750709	Cycle Pharmaceuticals Ltd.\|Parexel	Hereditary Tyrosinemia, Type I	October 2015	Phase 1
NCT00004333	National Center for Research Resources (NCRR)\|University of Michigan\|Office of Rare Diseases (ORD)	Tyrosinemia, Type I	November 1994	Phase 2
NCT04113772	Sutphin Drugs	Hereditary Tyrosinemia, Type I	November 1, 2019	Not Applicable
NCT02750332	Cycle Pharmaceuticals Ltd.\|Parexel	Hereditary Tyrosinemia, Type I	November 2015	Phase 1
NCT02323529	Swedish Orphan Biovitrum	Hereditary Tyrosinemia, Type I	December 2014	Phase 3
NCT01828463	University of Liverpool\|Liverpool University Hospitals NHS Foundation Trust	Alkaptonuria	May 2013	Phase 2
NCT00107783	National Human Genome Research Institute (NHGRI)\|National Institutes of Health Clinical Center (CC)	Alkaptonuria	January 2005	Phase 2
NCT01838655	National Eye Institute (NEI)\|National Human Genome Research Institute (NHGRI)\|National Institutes of Health Clinical Center (CC)	Albinism\|Vision Loss	April 16, 2013	Phase 1\|Phase 2

Appearance

Solid

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Solvent & Solubility

In Vitro:

DMSO : 41.67 mg/mL ( 126.57 mM ; Need ultrasonic)

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	3.0374 mL	15.1870 mL	30.3739 mL
5 mM	0.6075 mL	3.0374 mL	6.0748 mL
10 mM	0.3037 mL	1.5187 mL	3.0374 mL

* Please refer to the solubility information to select the appropriate solvent.

In Vivo:

1.

Add each solvent one by one: 10% DMSO >> 40% PEG300 >> 5% Tween-80 >> 45% saline

Solubility: ≥ 2.5 mg/mL (7.59 mM); Clear solution
2.

Add each solvent one by one: 10% DMSO >> 90% corn oil

Solubility: ≥ 2.5 mg/mL (7.59 mM); Clear solution

* All of the co-solvents are available by MCE.

References

Synonyms

1,3-Cyclohexanedione, 2-[2-nitro-4-(trifluoromethyl)benzoyl]-

2-[2-Nitro-4-(trifluoromethyl)benzoyl]-1,3-cyclohexanedione

Nitisinone

SC 0735

Orfadin

NTBC

Nitisone

Nityr