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MK-1775

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Chemical Structure| 955365-80-7 同义名 : -
CAS号 : 955365-80-7
货号 : A399066
分子式 : C27H32N8O2
纯度 : 98%
分子量 : 500.595
MDL号 : MFCD17215200
存储条件：

粉末 Keep in dark place,Sealed in dry,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 120 mg/mL(239.71 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

IP 2% DMSO+2% Tween80+40% PEG300+water 10 mg/mL clear

PO 0.5% CMC-Na 40 mg/mL suspension

生物活性
靶点

  • Wee1

    Wee1, IC50:5.2 nM
描述 Wee1 is a cellular protein kinase which inhibits Cdc2 activity, thereby preventing cells from proceeding through mitosis by maintaining G2 arrest. MK-1775 (AZD1775) is a first-in-class, pyrazolo-pyrimidine derivative and potent small-molecule inhibitor of Wee1 kinase with IC50 of 5.2 nM and blocks G2 DNA damage checkpoint[3]. In vitro, MK-1775 treatment at 500 nM for 48h caused S arrest or both S and G2/M arrest in human pancreatic cancer cell lines AsPC-1, BxPC-3, CFPAC-1, HPAC, MIAPaCa-2 and PANC-1[4]. In vivo, MK-1775 (20 mg/kg) twice daily combined with and panobinostat (10 mg/kg) once daily treatment in mice bearing BxPC-3 xenograft tumors, resulted in significant delay of tumor growth during the treatment period compared to single drug treatment, with 58.7% tumor growth inhibition on day 20[5]. The combination of gemcitabine (100 mg/kg, i.p., twice weekly on days 1 and 4, for 4 weeks) with MK-1775 (30 mg/kg. p.o., once daily for 4 weeks) produced robust antitumor activity and remarkably enhanced tumor regression response (4.01-fold) compared to gemcitabine treatment in p53-deficient tumors[6].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
A549 200 nM Apoptosis Assay 1 h radiosensitizes NSCLC cells in a p53-dependent manner 21799033
ASPC-1 Growth Inhibition Assay IC50=13.2 ± 1.1 μM 25458954
BxPC-3 Growth Inhibition Assay IC50=0.8 ± 0.03 μM 25458954
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT03385655 Prostate Cancer Phase 2 Recruiting December 31, 2020 Canada, Alberta ... 展开 >> Cross Cancer Institute Recruiting Edmonton, Alberta, Canada, T6G 1Z2 Contact: Michael Kolinsky    780 432-8762       Canada, British Columbia BCCA - Vancouver Cancer Centre Recruiting Vancouver, British Columbia, Canada, V5Z 4E6 Contact: Kim Chi    604 877-6000 ext 2746       Canada, Nova Scotia QEII Health Sciences Centre Recruiting Halifax, Nova Scotia, Canada, B3H 1V7 Contact: Robyn J. Macfarlane    902 473-6106       Canada, Ontario Juravinski Cancer Centre at Hamilton Health Sciences Recruiting Hamilton, Ontario, Canada, L8V 5C2 Contact: Som Mukherjee    905 387-9495 ext 64605       London Regional Cancer Program Recruiting London, Ontario, Canada, N6A 5W9 Contact: Eric W. Winquist    519 685-8261       Ottawa Hospital Research Institute Recruiting Ottawa, Ontario, Canada, K1H 8L6 Contact: Michael Ong    613 737-7700 ext 75051       University Health Network Recruiting Toronto, Ontario, Canada, M5G 2M9 Contact: Adrian Sacher    416 946-4501 ext 3550       Canada, Quebec CHUM-Centre Hospitalier de l'Universite de Montreal Recruiting Montreal, Quebec, Canada, H2X 3E4 Contact: Fred Saad    514 890-8000 ext 27466       The Jewish General Hospital Recruiting Montreal, Quebec, Canada, H3T 1E2 Contact: Cristiano Ferrario    514 398-8307       Canada, Saskatchewan Allan Blair Cancer Centre Recruiting Regina, Saskatchewan, Canada, S4T 7T1 Contact: Muhammad Salim    306 766-2691       Saskatoon Cancer Centre Recruiting Saskatoon, Saskatchewan, Canada, S7N 4H4 Contact: Nayyer Iqbal    306 655-2710 收起 <<
NCT02546661 Muscle Invasive Bladder Cancer Phase 1 Recruiting March 27, 2020 -
NCT02813135 Children, Adolescents and Youn... 展开 >>g Adults With Refractory or Recurrent Malignancies 收起 << Phase 1 Phase 2 Recruiting January 2022 France ... 展开 >> Gustave Roussy Recruiting Villejuif, Val De Marne, France, 94805 Contact: Birgit Geoerger, MD    1 42 11 4661 ext +33    birgit.geoerger@gustaveroussy.fr    Contact: Xavier Paoletti, MD    1 42 11 6564 ext +33    xavier.paoletti@gustaveroussy.fr    Principal Investigator: Birgit Geoerger, MD          Germany University Children's Hospitalermany Not yet recruiting Heidelberg, Germany Contact: Olaf Witt, MD    6221 56 4555 ext +49    O.Witt@Dkfz-Heidelberg.de    Italy Fondazione IRCCS Istituto Nazionale dei Tumori Not yet recruiting Milan, Italy Contact: Michela Casanova, MD    02 23 90 25 94 ext +39    Michela.Casanova@istitutotumori.mi.it    Netherlands Erasmus MC, Sophia Children's Hospital Not yet recruiting Rotterdam, Netherlands Contact: Michel Zwaan, MD    10 703 6691 ext +31    c.m.zwaan@erasmusmc.nl    Spain Unidad de Oncología Pediátrica Hospital Niño Jesús Not yet recruiting Madrid, Spain, 28009 Contact: Francisco Bautista, MD    915 035 900 ext +43    franciscojose.bautista@salud.madrid.org    United Kingdom Pediatric and Adolescent Oncology The Royal Marsden Hospital Not yet recruiting Sutton, United Kingdom Contact: Lynley Marshall, MD    208 661 3678 ext +44    Lynley.Marshall@icr.ac.uk 收起 <<
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.00mL

0.40mL

0.20mL

9.99mL

2.00mL

1.00mL

19.98mL

4.00mL

2.00mL
参考文献

[1]Do K, Wilsker D, Ji J, Zlott J, Freshwater T, Kinders RJ, Collins J, Chen AP, Doroshow JH, Kummar S. Phase I Study of Single-Agent AZD1775 (MK-1775), a Wee1 Kinase Inhibitor, in Patients With Refractory Solid Tumors. J Clin Oncol. 2015 Oct 20;33(30):3409-15. doi: 10.1200/JCO.2014.60.4009. Epub 2015 May 11. PMID: 25964244; PMCID: PMC4606059.

[2]Wang G, Niu X, Zhang W, Caldwell JT, Edwards H, Chen W, Taub JW, Zhao L, Ge Y. Synergistic antitumor interactions between MK-1775 and panobinostat in preclinical models of pancreatic cancer. Cancer Lett. 2015 Jan 28;356(2 Pt B):656-68. doi: 10.1016/j.canlet.2014.10.015. Epub 2014 Oct 18. PMID: 25458954; PMCID: PMC4282784.

[3]Wang G, Niu X, Zhang W, Caldwell JT, Edwards H, Chen W, Taub JW, Zhao L, Ge Y. Synergistic antitumor interactions between MK-1775 and panobinostat in preclinical models of pancreatic cancer. Cancer Lett. 2015 Jan 28;356(2 Pt B):656-68. doi: 10.1016/j.canlet.2014.10.015. Epub 2014 Oct 18. PMID: 25458954; PMCID: PMC4282784.

[4]Rajeshkumar NV, De Oliveira E, Ottenhof N, Watters J, Brooks D, Demuth T, Shumway SD, Mizuarai S, Hirai H, Maitra A, Hidalgo M. MK-1775, a potent Wee1 inhibitor, synergizes with gemcitabine to achieve tumor regressions, selectively in p53-deficient pancreatic cancer xenografts. Clin Cancer Res. 2011 May 1;17(9):2799-806. doi: 10.1158/1078-0432.CCR-10-2580. Epub 2011 Mar 9. PMID: 21389100; PMCID: PMC3307341.