| 名称 | Prexasertib |
| 描述 | Prexasertib (LY2606368) is a selective checkpoint kinase 1 (CHK1) inhibitor (Ki 0.9 nM, IC50<1 nM). Prexasertib causes double-stranded DNA breaks and replication mutations, leading to apoptosis. Prexasertib has antitumor activity. |
| 细胞实验 | LY2606368 is broadly antiproliferative with IC50s of 3 nM, 3 nM, 10 nM, 37 nM, and 68 nM against U-2 OS, Calu-6, HT-29, HeLa, and NCI-H460 cell lines, respectively. LY2606368 (25 μM) exhibits inhibitory activities against proliferation of AGS and MKN1 cells. LY2606368 (20 nM) inhibits HR repair capacity DR-GFP cells. |
| 动物实验 | LY2606368 is formulated in vehicle consisting of 20% Captisol.Female CD-1 nu-/nu- mice (26-28 g) are used for this study. Tumor growth is initiated by subcutaneous injection of 1×106 Calu-6 cells in a 1:1 mixture of serum-free growth medium and Matrigel in the rear flank of each subject animal. When tumor volumes reach approximately 150 mm3 in size, the animals are randomized by tumor size and body weight, and placed into their respective treatment groups. Vehicle consisting of 20% Captisol pH4 or LY2606368 is administered by subcutaneous injection in a volume of 200 μL. Four, eight, 12, 24, and 48 hours after drug administration, blood for plasma drug exposure is extracted via cardiac puncture and assayed on a Sciex API 4000 LC/MS-MS system. The xenograft tissue is promptly removed and prepared. Lysates are analyzed by immunoblot analysis for protein phosphorylation levels. Group means, SEs and P values are calculated using Kronos. |
| 体外活性 | 方法：人JeKo1、MV4-11、Ramos、RPMI-8226、Z-138细胞用Prexasertib（0-50 μM）处理72小时，通过CellTiter 96 Aqueous One Solution试剂基于的测定法检测细胞生长抑制情况。
结果：Prexasertib抑制JeKo1（IC50=0.004 μM）、MV4-11（IC50=0.004 μM）、Ramos（IC50=0.004 μM）、RPMI-8226（IC50=0.048 μM）、Z-138（IC50=0.033 μM）细胞生长。[1] |
| 体内活性 | 方法：为研究Prexasertib的抗肿瘤活性，将Prexasertib（1-10 mg/kg）皮下注射给小鼠，每天两次，连续3天，休息4天；进行三周。
结果：Prexasertib可抑制肿瘤异种移植瘤的生长。[2] |
| 存储条件 | The compound is unstable in solution. Please use soon,
Powder: -20°C for 3 years
Shipping with blue ice/Shipping at ambient temperature. |
| 溶解度 | DMSO : 22 mg/mL (60.21 mM), Sonication is recommended. The compound is unstable in solution. Please use soon.
10% DMSO+40% PEG300+5% Tween 80+45% Saline : 1 mg/mL (2.74 mM), Sonication is recommended.
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| 关键字 | SIK | S516 | S296 | RSK1 | replication | Prexasertib | MELK | LY-2606368 | LY 2606368 | Inhibitor | inhibit | HT-29 | HeLa | H2AX | double-stranded | DNA | Chk2 | Chk1 | Checkpoint Kinase (Chk) | CDK2 | CDC25A | BRSK2 | autophosphorylation | ATP-competitive | ARK5 | Apoptosis |
| 相关产品 | Formamide | Urea | Sodium Molybdate | Dimethyl phthalate | Aceglutamide | Alginic acid | Cysteamine hydrochloride | Metronidazole | Sildenafil citrate | Citric Acid Triammonium | Stavudine | Tamoxifen |
| 相关库 | 抑制剂库 | 经典已知活性库 | 抗癌活性化合物库 | 已知活性化合物库 | 激酶抑制剂库 | 抗衰老化合物库 | 抗病毒库 | 药物功能重定位化合物库 | 抗癌临床化合物库 | 儿童药物库 | 共价抑制剂库 | 抗癌药物库 |