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，Ki 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。
| CAS No. | 1234015-54-3 |
| 生物活性 | Prexasertib dihydrochloride (LY2606368 dihydrochloride) is a selective, ATP-competitive second-generation checkpoint kinase 1 (CHK1) inhibitor with a Ki 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. |
| 分子式 | C18H19N7O2.HCl |
| 分子量 | 438.31 |
| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存条件 | 4°C, sealed storage, away from moisture |
| 溶解性数据 | DMSO : 8 mg/mL (18.25 mM; Need ultrasonic) H2O : < 0.1 mg/mL (insoluble) |
| 体内研究 | 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). |
| 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. |
| 文献 | •Nat Commun. 2019 Aug 2;10(1):3485. •Thorax. 2021 Jul 5;thoraxjnl-2021-217377. •Br J Cancer. 2021 Mar 26. •Cell Biol Toxicol. 2021 Sep 14. •Cancers (Basel). 2021 Aug 20;13(16):4200. •Cancers. 2020 Aug 26;12(9):2426. •Cancers. 2020 Jun 29;12(7):1726. •Mol Cancer Res. 2019 Oct;17(10):2102-2114. •Sci Rep. 2021 Feb 4;11(1):3176. •bioRxiv. January 04, 2022. •Patent. US20210353605A1. •bioRxiv. September 10, 2021. •Research Square Preprint. 2021 May. •Methods Mol Biol. 2018;1711:351-398. |
| 纯度及产品资料 | 98% |
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