生物活性

• 靶点	Wee1 IC50:5.2nM

• 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
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  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

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• 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 ... more >> 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 Collapse <<
  NCT02546661	Muscle Invasive Bladder Cancer	Phase 1	Recruiting	March 27, 2020	-
  NCT02813135	Children, Adolescents and Youn... more >>g Adults With Refractory or Recurrent Malignancies Collapse <<	Phase 1 Phase 2	Recruiting	January 2022	France ... more >> 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 Collapse <<

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