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[CAS NO. 104206-65-7] Nitisinone
| Ships within | Stock | Price | Qty | Total |
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| Catalog: | HY-B0607 |
| Brand: | MCE |
| CAS: | 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 |
1 Publications Citing Use of MCE
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
DMSO : 41.67 mg/mL ( 126.57 mM ; Need ultrasonic)
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 |
-
1.
-
2.
Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 2.5 mg/mL (7.59 mM); Clear solution
References
- [1] Laschi M, et al. Inhibition of para-Hydroxyphenylpyruvate Dioxygenase by Analogues of the Herbicide Nitisinone As a Strategy to Decrease Homogentisic Acid Levels, the Causative Agent of Alkaptonuria. ChemMedChem. 2016 Apr 5;11(7):674-8.
- [2] Ellis MK, et al. Inhibition of 4-hydroxyphenylpyruvate dioxygenase by 2-(2-nitro-4-trifluoromethylbenzoyl)-cyclohexane-1,3-dione and 2-(2-chloro-4-methanesulfonylbenzoyl)-cyclohexane-1,3-dione. Toxicol Appl Pharmacol. 1995 Jul;133(1):12-9.
- [3] Onojafe IF, et al. Nitisinone improves eye and skin pigmentation defects in a mouse model of oculocutaneous albinism. J Clin Invest. 2011 Oct;121(10):3914-23.
- [4] Aktuglu-Zeybek A, et al. Nitisinone: a review. Orphan Drugs: Research and Reviews, 2017, 7.
Synonyms
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