Adavosertib-AZD1775-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEAdavosertibCat. No.: HY-10993CAS No.: 955365-80-7Synonyms: AZD1775; MK-1775分式: CHNO分量: 500.6作靶點: Wee1作通路: Cell Cycle/DNA Damage儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 18.75 mg/mL (3

2、7.46 mM; Need ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 1.9976 mL 9.9880 mL 19.9760 mL5 mM 0.3995 mL 1.9976 mL 3.9952 mL10 mM 0.1998 mL 0.9988 mL 1.9976 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。體內(nèi)實驗請根據(jù)您的實驗動物和給藥式選擇適當(dāng)?shù)娜芙獍?，配制前請先配制澄清的儲備液，再依次添加助溶?為保證實驗結(jié)果的可靠性，體內(nèi)實驗的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使；澄

3、清的儲備液可以根據(jù)儲存條件，適當(dāng)保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.08 mg/mL (4.16 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.08 mg/mL (4.16 mM); Clear solution3. 請依序添加每種溶劑： 10% DMSO 90% corn oil1/3 Master of Smal

4、l Molecules 您邊的抑制劑師www.MedChemESolubility: 2.08 mg/mL (4.16 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Adavosertib (AZD-1775; MK-1775)種有效的 Wee1 抑制劑，IC50 值為 5.2 nM。IC50 & Target IC50: 5.2 nM (Wee1)體外研究 Adavosertib (MK-1775) enhances the cytotoxic effects of 5-FU in p53-deficient human colon cancer cel

5、ls.Adavosertib (MK-1775) inhibits CDC2 Y15 phosphorylation in cells, abrogates DNA damaged checkpointsinduced by 5-FU treatment, and causes premature entry of mitosis determined by induction of Histone H3phosphorylation 1. Adavosertib (MK-1775) abrogates the radiation-induced G2 block in p53-defecti

6、ve cellsbut not in p53 wild-type lines 2. The combination of NSC 613327 with Adavosertib (MK-1775) producesrobust anti-tumor activity and remarkably enhances tumor regression response (4.01 fold) compared to NSC613327 treatment in p53-deficient tumors 3.體內(nèi)研究 In vivo, Adavosertib (MK-1775) potentiate

7、s the anti-tumor efficacy of 5-FU at tolerable doses 1. Adavosertib(MK-1775) (60 mg/kg twice daily, p.o.) enhances H1299 xenograft tumor response to fractionatedradiotherapy 2. Adavosertib (MK-1775) (30 mg/kg. p.o.) regresses tumor growth in PANC198, PANC215and PANC185 as compared to GEM treated mic

8、e 3.PROTOCOLCell Assay 2 Total protein is extracted from the cell pellet using a lysis solution containing 50 mM HEPES (pH 7.9), 0.4mol/L NaCl, and 1 mM EDTA and fortified with 10 L/mL phosphatase inhibitor cocktail 1, 10 L/mLphosphatase inhibitor cocktail 2, 10 L/mL protease inhibitor, and 1% NP-40

9、. Protein concentration of thelysates is determined by the Bio-Rad protein assay. Equal amounts of protein are separated by 12% SDS-PAGE and transferred to an Immobilon membrane. Nonspecific binding sites on the membrane are blockedin 5% nonfat dry milk in Tris (20 mM)-buffered saline (150 mM, pH 7.

10、4) with 0.1% Tween (TBS-T). Proteinsignals are detected by incubating the membrane in primary antibody in 5% nonfat dry milk overnight at 4C,followed by a 45-min incubation in the appropriate peroxidase-conjugated secondary antibody. Themembrane is then developed by enhanced chemiluminescence with E

11、CL plus Western Blotting DetectionReagents on a Typhoon 9400 scanner.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Tumor xenografts are produced in the leg by im inoculation of 1106 Calu-6 cells in 10 L. Irradiation andAdministration 2 Adavoser

12、tib (MK-1775) treatment are started when tumors reach 8 mm diameter and continue for 5 days.Gamma-rays are delivered locally to the tumor-bearing legs of unanesthetized mice using a small-animalirradiator consisting of two parallel-opposed 137Cs sources, at a dose rate of 5 Gy/min. Tumors areirradia

13、ted twice daily separated by 6 h. Adavosertib (MK-1775) is given by gavage in 0.1 mL volumes 1 hbefore and 2 h after the first daily radiation dose.MCE has not independently confirmed the accuracy of these methods. They are for reference only.2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE戶使本產(chǎn)品發(fā)表的

14、科研獻(xiàn) Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093. J Hematol Oncol. 2018 Aug 1;11(1):99. Cancer Res. 2017 Sep 1;77(17):4663-4672. Sci Rep. 2019 Apr 23;9(1):6458. PLoS One. 2019 Jan 10;14(1):e0209224.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Hirai H, et al. MK-1775, a

15、 small molecule Wee1 inhibitor, enhances anti-tumor efficacy of various DNA-damaging agents, including 5-FU. Cancer Biol Ther. 2010 Apr;9(7):514-22.2. Bridges KA, et al. MK-1775, a novel Wee1 kinase inhibitor, radiosensitizes p53-defective human tumor cells. Clin Cancer Res. 2011 Sep1;17(17):5638-48. Epub 2011 Jul 28.3. Rajeshkumar NV, et al. MK-1775, a potent Wee1 inhibitor, synergizes with NSC 613327 to achieve tumor regressions, selectively inp53-deficient pancreatic cancer xenografts.Clin Cancer Res. 2011 Ma