CAS號	104206-65-7	產(chǎn)地	國產(chǎn)
規(guī)格	10mg	級別	化工級
證書	ISO系列證書

Nitisinone (Synonyms: 尼替西農(nóng); NTBC; Nitisone; SC0735)

Nitisinone 是一種口服有效的，具有競爭性和可逆性的 4-羥苯丙tong酸二加氧酶 (4-HPPD) 抑制劑，其 IC₅₀ 值為 173 nM。Nitisinone 能以劑量依賴的方式促進酪an酸的積累。Nitisinone 可用于遺傳性酪an酸血癥 1 型 (HT-1) (罕見的遺傳性疾病) 和白化病的研究。

生物活性

Nitisinone is an orally active, competitive and reversible 4-hydroxyphenylpyruvate dioxygenase (4-HPPD) inhibitor with an IC₅₀ 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].

體外研究(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.

體內(nèi)研究(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).

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

分子量：329.23

Formula：C₁₄H₁₀F₃NO₅

CAS 號：104206-65-7

中文名稱：尼替西農(nóng)

運輸條件：Room temperature in continental US; may vary elsewhere.

儲存方式

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

溶解性數(shù)據(jù)

In Vitro:

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

配制儲備液

濃度溶劑體積質(zhì)量	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

請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；一旦配成溶液，請分裝保存，避免反復凍融造成的產(chǎn)品失效。
儲備液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 儲存時，請在 6 個月內(nèi)使用，-20°C 儲存時，請在 1 個月內(nèi)使用。

In Vivo:

以下溶解方案都請先按照 In Vitro 方式配制澄清的儲備液，再依次添加助溶劑：

——為保證實驗結(jié)果的可靠性，澄清的儲備液可以根據(jù)儲存條件，適當保存；體內(nèi)實驗的工作液，建議您現(xiàn)用現(xiàn)配，當天使用；以下溶劑前顯示的百
分比是指該溶劑在您配制終溶液中的體積占比；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的方式助溶

1.

請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% saline
Solubility: ≥ 2.5 mg/mL (7.59 mM); Clear solution
2.

請依序添加每種溶劑： 10% DMSO 90% corn oil
Solubility: ≥ 2.5 mg/mL (7.59 mM); Clear solution

參考文獻

[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. [Content Brief]
[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. [Content Brief]
[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. [Content Brief]
[4]. Aktuglu-Zeybek A, et al. Nitisinone: a review. Orphan Drugs: Research and Reviews, 2017
注：產(chǎn)品僅用于科研