Prexasertib dihydrochloride LY2606368 dihydrochloride|cas:1234015-54-3|西域试剂

Prexasertib dihydrochloride LY2606368 dihydrochloride,99.41%

产品编号：Bellancom-18174A| CAS NO：1234015-54-3| 分子式：C₁₈H₂₁Cl₂N₇O₂| 分子量：438.31

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货号	价格	库存与货期
Bellancom-18174A	￥700.00	杭州北京（现货）
Bellancom-18174A	￥1300.00	杭州北京（现货）
Bellancom-18174A	￥2300.00	杭州北京（现货）
Bellancom-18174A	￥4600.00	杭州北京（现货）
Bellancom-18174A	￥7800.00	杭州北京（现货）

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Prexasertib dihydrochloride LY2606368 dihydrochloride

产品介绍

Prexasertib dihydrochloride (LY2606368 dihydrochloride) 是一种选择性的，ATP 竞争性的第二代细胞周期检测点激酶 1 (CHK1) 抑制剂，K_i 为 0.9 nM，IC₅₀ 为 <1 nM。Prexasertib dihydrochloride 抑制 CHK2 (IC₅₀=8 nM) 和 RSK1 (IC₅₀=9 nM)。Prexasertib dihydrochloride 引起双链 DNA 断裂和复制突变，导致细胞凋亡 (apoptosis)。Prexasertib dihydrochloride 显示有效的抗肿瘤活性。

生物活性

Prexasertib dihydrochloride (LY2606368 dihydrochloride) is a selective, ATP-competitive second-generation checkpoint kinase 1 (CHK1) inhibitor with a K_i of 0.9 nM and an IC₅₀ of <1 nM. Prexasertib dihydrochloride inhibits CHK2 (IC₅₀=8 nM) and RSK1 (IC₅₀=9 nM). Prexasertib dihydrochloride causes double-stranded DNA breakage and replication catastrophe resulting in apoptosis. Prexasertib dihydrochloride shows potent anti-tumor activity.

体外研究

Prexasertib dihydrochloride (LY2606368 dihydrochloride) inhibits MELK (IC₅₀=38 nM), SIK (IC₅₀=42 nM), BRSK2 (IC₅₀=48 nM), ARK5 (IC₅₀=64 nM). LY2606368 requires CDC25A and CDK2 to cause DNA damage.
Prexasertib dihydrochloride (33, 100 nM; for 7 hours) results in DNA damage during S-phase in HeLa cells.
Prexasertib dihydrochloride (8-250 nM; pre-treated for 15 minutes) inhibits CHK1 autophosphorylation (S296) and CHK2 autophosphorylation (S516) in HT-29 cells.
Prexasertib dihydrochloride (4 nM; 24 hours) results in a large shift in cell-cycle populations from G1 and G2-M to S-phase with an accompanied induction of H2AX phosphorylation in U-2 OS cells.
Prexasertib dihydrochloride (33 nM; for 12 hours) causes chromosomal fragmentation in HeLa cells. Prexasertib (100 nM; 0.5 to 9 hours) induces replication stress and depletes the pool of available RPA2 for binding to DNA.

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

Cell Cycle Analysis

Cell Line:	HeLa cells
Concentration:	33, 100 nM
Incubation Time:	For 7 hours
Result:	Had an IC₅₀ of 37 nM and resulted in the G2-M population received DNA damage during S-phase but continued to progress through the cell cycle into an early mitosis.

Western Blot Analysis

Cell Line:	HT-29 cells
Concentration:	8, 16, 31, 63, 125, 250 nM
Incubation Time:	Pre-treated for 15 minutes
Result:	Inhibited CHK1 autophosphorylation (S296) and CHK2 autophosphorylation (S516) (IC₅₀ of less than 31 nM) in HT-29 cells.

体内研究
(In Vivo)

Prexasertib dihydrochloride (LY2606368 dihydrochloride; 1-10 mg/kg; SC; twice daily for 3 days, rest 4 days; for three cycles) causes growth inhibition in tumor xenografts.
Prexasertib dihydrochloride (15 mg/kg; SC) causes CHK1 inhibition in the blood and the phosphorylation of both H2AX (S139) and RPA2 (S4/S8).

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

Animal Model:	Female CD-1 nu-/nu- mice (26-28 g) with Calu-6 cells
Dosage:	1, 3.3, or 10 mg/kg
Administration:	SC; twice daily for 3 days, rest 4 days; for three cycles
Result:	Caused statistically significant tumor growth inhibition (up to 72.3%).

Animal Model:	Female CD-1 nu-/nu- mice (26-28 g) with Calu-6 cells
Dosage:	15 mg/kg (Pharmacokinetic Analysis)
Administration:	SC (200 μL)
Result:	CHK1 was 7 ng/mL at 12 hours and 3 ng/mL by 24 hours in plasma exposures. Phosphorylation of both H2AX (S139) and RPA2 (S4/S8) was detectable at 4 hours, showing the rapid occurrence of DNA damage.

体内研究

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

Animal Model:	Female CD-1 nu-/nu- mice (26-28 g) with Calu-6 cells
Dosage:	1, 3.3, or 10 mg/kg
Administration:	SC; twice daily for 3 days, rest 4 days; for three cycles
Result:	Caused statistically significant tumor growth inhibition (up to 72.3%).

Animal Model:	Female CD-1 nu-/nu- mice (26-28 g) with Calu-6 cells
Dosage:	15 mg/kg (Pharmacokinetic Analysis)
Administration:	SC (200 μL)
Result:	CHK1 was 7 ng/mL at 12 hours and 3 ng/mL by 24 hours in plasma exposures. Phosphorylation of both H2AX (S139) and RPA2 (S4/S8) was detectable at 4 hours, showing the rapid occurrence of DNA damage.

体内研究

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

Animal Model:	Female CD-1 nu-/nu- mice (26-28 g) with Calu-6 cells
Dosage:	1, 3.3, or 10 mg/kg
Administration:	SC; twice daily for 3 days, rest 4 days; for three cycles
Result:	Caused statistically significant tumor growth inhibition (up to 72.3%).

Animal Model:	Female CD-1 nu-/nu- mice (26-28 g) with Calu-6 cells
Dosage:	15 mg/kg (Pharmacokinetic Analysis)
Administration:	SC (200 μL)
Result:	CHK1 was 7 ng/mL at 12 hours and 3 ng/mL by 24 hours in plasma exposures. Phosphorylation of both H2AX (S139) and RPA2 (S4/S8) was detectable at 4 hours, showing the rapid occurrence of DNA damage.

性状

Solid

溶解性数据

In Vitro:

DMSO : 8 mg/mL (18.25 mM; Need ultrasonic)

H₂O : 1 mg/mL (2.28 mM; ultrasonic and warming and heat to 80°C)

配制储备液

浓度溶剂体积质量	1 mg	5 mg	10 mg

1 mM	2.2815 mL	11.4075 mL	22.8149 mL
5 mM	0.4563 mL	2.2815 mL	4.5630 mL
10 mM	0.2281 mL	1.1407 mL	2.2815 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°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)。-80°C 储存时，请在 6 个月内使用，-20°C 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 40% PEG300 5% Tween-80 45% saline
Solubility: ≥ 0.8 mg/mL (1.83 mM); Clear solution

此方案可获得 ≥ 0.8 mg/mL (1.83 mM，饱和度未知) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 8.0 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
2.

请依序添加每种溶剂： 10% DMSO 90% (20% SBE-β-CD in saline)
Solubility: ≥ 0.8 mg/mL (1.83 mM); Clear solution

此方案可获得 ≥ 0.8 mg/mL (1.83 mM，饱和度未知) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 8.0 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 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