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Prexasertib dimesylate
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。
Prexasertib dimesylate图片
CAS NO:1234015-58-7
包装与价格:
包装价格(元)
10 mM * 1 mL in DMSO电议
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
200mg电议
500mg电议

产品名称
LY2606368 dimesylate
产品介绍
Prexasertib dimesylate (LY2606368 dimesylate) 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,Ki为 0.9 nM,IC50为<1 nm。prexasertib dimesylate 抑制 CHK2 (IC50=8 nM) 和 RSK1 (IC50=9 nM)。Prexasertib dimesylate 引起双链 DNA 断裂和复制突变,导致细胞凋亡 (apoptosis)。Prexasertib dimesylate 显示有效的抗肿瘤活性。
生物活性

Prexasertib dimesylate (LY2606368 dimesylate) is a selective, ATP-competitive second-generationcheckpoint kinase 1 (CHK1)inhibitor with aKiof 0.9 nM and anIC50of<1 nm. prexasertib dimesylate inhibitsCHK2(IC50=8 nM) andRSK1(IC50=9 nM). Prexasertib dimesylate causes double-stranded DNA breakage and replication catastrophe resulting inapoptosis. Prexasertib dimesylate shows potent anti-tumor activity[1][2].

IC50& Target[1]

Chk1

0.9 nM (Ki)

Chk1

<1 nM (IC50)

Chk2

8 nM (IC50)

体外研究
(In Vitro)

Prexasertib dimesylate (LY2606368 dimesylate) inhibits MELK (IC50=38 nM), SIK (IC50=42 nM), BRSK2 (IC50=48 nM), ARK5 (IC50=64 nM). Prexasertib dimesylate requires CDC25A and CDK2 to cause DNA damage[1].
Prexasertib dimesylate (33, 100 nM; for 7 hours) results in DNA damage during S-phase in HeLa cells[1].
Prexasertib dimesylate (8-250 nM; pre-treated for 15 minutes) inhibits CHK1 autophosphorylation (S296) and CHK2 autophosphorylation (S516) in HT-29 cells[1].
Prexasertib dimesylate (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[1].
Prexasertib dimesylate (33 nM; for 12 hours) causes chromosomal fragmentation in HeLa cells. Prexasertib dimesylate (100 nM; 0.5 to 9 hours) induces replication stress and depletes the pool of available RPA2 for binding to DNA[1].

Cell Cycle Analysis[1]

Cell Line:HeLa cells
Concentration:33, 100 nM
Incubation Time:For 7 hours
Result:Had an IC50of 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[1]

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) (IC50of less than 31 nM) in HT-29 cells.
体内研究
(In Vivo)

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

Animal Model:Female CD-1 nu-/nu- mice (26-28 g) with Calu-6 cells[1]
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[1]
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.
Clinical Trial
分子量

557.60

性状

Solid

Formula

C20H27N7O8S2

CAS 号

1234015-58-7

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式

4°C, stored under nitrogen

*In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)

溶解性数据
In Vitro: 

DMSO : 100 mg/mL(179.34 mM;Need ultrasonic)

H2O : 50 mg/mL(89.67 mM;Need ultrasonic)

配制储备液
浓度溶剂体积质量1 mg5 mg10 mg
1 mM1.7934 mL8.9670 mL17.9340 mL
5 mM0.3587 mL1.7934 mL3.5868 mL
10 mM0.1793 mL0.8967 mL1.7934 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 (stored under nitrogen)。-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    40%PEG300   5%Tween-80   45% saline

    Solubility: ≥ 3.5 mg/mL (6.28 mM); Clear solution

    此方案可获得 ≥ 3.5 mg/mL (6.28 mM,饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例,取 100 μL 35.0 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-CDin saline)

    Solubility: ≥ 3.5 mg/mL (6.28 mM); Clear solution

    此方案可获得 ≥ 3.5 mg/mL (6.28 mM,饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例,取 100 μL 35.0 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。