Lestaurtinib

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Lestaurtinib

本产品不向个人销售，仅用作科学研究，不用于任何人体实验及非科研性质的动物实验。

CAS NO:

111358-88-4

来他替尼
CEP-701
KT-5555

Lestaurtinib 是一种口服有效的选择性受体酪氨酸激酶抑制剂，能竞争性地抑制 ATP 与TrkA/B/C激酶结合。Lestaurtinib 可抑制RPTKs的磷酸化，其对FLT3、TrkA、JAK2的IC₅₀值分别为 2, 25 和 0.9 nM。Lestaurtinib 能诱导细胞凋亡和周期停滞，可显著抑制肿瘤的生长。

生物活性

Lestaurtinib (CEP-701) is an orally active and selectiveRPTKs (receptor protein tyrosine kinase)inhibitor, competitively inhibits ATP binding to theTrkA/B/Cdomain. Lestaurtinib inhibitsRPTKsphosphorylation, withIC₅₀s of 2, 25 and 0.9 nM forFLT3,TrkAandJAK2, respectively. Lestaurtinib inducesapoptosisand cycle arrest, also can inhibit growth of tumor^[1]^[2]^[3]^[4]^[5]^[6].

IC₅₀& Target^[1]

JAK2

0.9 nM (IC₅₀)

TrkA

25 nM (IC₅₀)

FLT3

2 nM (IC₅₀)

体外研究
(In Vitro)

Lestaurtinib (0.01-10 μM; 72 h) inhibits growth of ATC cells, with IC₅₀s of 0.21, 0.41 and 2.35 μM for KMH2, CAL62 and THJ-21T cells, respectively^[1].
Lestaurtinib (0.125-4 μM; 24 h) decreases STAT5 phosphorylation in a concentration-dependent manner, and completely inhibits expression of pSTAT5 at 4 μM^[1].
Lestaurtinib (0.5 μM; 24 h) shows antiproliferative effect on WI-38, CAL62 and KMH2 cells^[1].
Lestaurtinib (4 μM; 24 h) induces cell cycle arrest in the G2/M phase in CAL62 and KMH2 cells^[1].
Lestaurtinib (30-300 nM; 48 h) induces apoptosis in a dose-dependent manner in HL (hodgkin lymphoma) cell lines^[2].
Lestaurtinib (30, 100, 300 nM; 1 h) inhibits JAK2, STAT5 and STAT3 phosphorylation when at 300 nM^[2].

Cell Viability Assay^[1]

Cell Line:	KMH2, CAL62, THJ-21T cells
Concentration:	0.01-10 μM
Incubation Time:	72 h
Result:	Showed good growth inhibitory activity with IC₅₀s of 0.21, 0.41 and 2.35 μM for KMH2, CAL62 and THJ-21T cells, respectively.

Cell Proliferation Assay^[1]

Cell Line:	WI-38, CAL62 and KMH2 cells
Concentration:	0.5 μM
Incubation Time:	24 h
Result:	Inhibited proliferation of ATC cells.

Cell Cycle Analysis^[1]

Cell Line:	CAL62 and KMH2 cells
Concentration:	4 μM
Incubation Time:	24 h
Result:	Led to increase in the number of cells in the G2/M phase, and decrease in the number of cells in the G1/G0 and S phases (KMH2 cells more significant than CAL62 cells).

Western Blot Analysis^[1]

Cell Line:	CAL62 cells
Concentration:	0.125-4 μM
Incubation Time:	24 h
Result:	Decreased pSTAT5 in a concentration-dependent manner, with a complete disappearance of pSTAT5expression at 4 μM.

Apoptosis Analysis^[2]

Cell Line:	L-428, L-1236, L-540, HDLM-2 and HDMY-Z cells
Concentration:	30-300 nM
Incubation Time:	48 h
Result:	Increased apoptosis rate of 62%, 57%, 10%, 64%, 30% for L-428, L-1236, L-540, HDLM-2 and HD-MY-Z cells respectively, when at 300 nM (in a dose-dependent manner).

Western Blot Analysis^[2]

Cell Line:	L-428, L-1236, L-540, HDLM-2 and HD-MY-Z cells
Concentration:	30, 100, 300 nM
Incubation Time:	1 h
Result:	Decreased phospho-JAK2, -STAT5 and -STAT3 levels of all the HL cell lines by 46-94%, 88-100% and 97-100%, respectively (when at 300 nM).

体内研究
(In Vivo)

Lestaurtinib (20 mg/kg; s.c.; twice daily (monday to friday) and once daily (saturday and sunday); 3 weeks) significantly inhibits growth of tumor in vivo^[3].

Animal Model:	Four-week-old athymic nu/nu mice (SY5Y-TrkB xenografts model)^[3].
Dosage:	20 mg/kg
Administration:	Subcutaneous injection; twice daily (monday to friday) and once daily (saturday and sunday); 3 weeks.
Result:	Significantly slowed the growth of SY5Y-TrkB xenografts.

Clinical Trial

分子量

439.46

性状

Solid

Formula

C₂₆H₂₁N₃O₄

CAS 号

111358-88-4

中文名称

来他替尼

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式

-20°C, protect from light

*In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)

溶解性数据

In Vitro:

DMSO : 50 mg/mL(113.78 mM;Need ultrasonic)

配制储备液

浓度溶剂体积质量

1 mg

5 mg

10 mg

1 mM	2.2755 mL	11.3776 mL	22.7552 mL
5 mM	0.4551 mL	2.2755 mL	4.5510 mL
10 mM	0.2276 mL	1.1378 mL	2.2755 mL

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month (protect from light)。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

1.
请依序添加每种溶剂： 10% DMSO 90%corn oil
Solubility: 2.5 mg/mL (5.69 mM); Suspended solution; Need ultrasonic
此方案可获得 2.5 mg/mL (5.69 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。
以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。
2.
请依序添加每种溶剂： 10% DMSO 40%PEG300 5%Tween-80 45% saline
Solubility: ≥ 2.08 mg/mL (4.73 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (4.73 mM，饱和度未知) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。
将 0.9 g 氯化钠，完全溶解于 100 mL ddH2O 中，得到澄清透明的生理盐水溶液
3.
请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline)
Solubility: ≥ 2.08 mg/mL (4.73 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (4.73 mM，饱和度未知) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。
将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明

*以上所有助溶剂都可在本网站选购。