1. Cell Cycle/DNA Damage
  2. Wee1

MK-1775 (Synonyms: AZD-1775; AZD1775; AZD 1775)

Cat. No.: HY-10993 Purity: 98.96%
Data Sheet SDS Handling Instructions

MK-1775 is a potent Wee1 inhibitor with IC50 of 5.2 nM.

For research use only. We do not sell to patients.
MK-1775 Chemical Structure

MK-1775 Chemical Structure

CAS No. : 955365-80-7

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10 mM * 1 mL in DMSO $77 In-stock
5 mg $70 In-stock
10 mg $90 In-stock
50 mg $250 In-stock
100 mg $450 In-stock
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500 mg   Get quote  

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  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

MK-1775 is a potent Wee1 inhibitor with IC50 of 5.2 nM.

IC50 & Target

IC50: 5.2 nM (Wee1)

In Vitro

MK-1775 enhances the cytotoxic effects of 5-FU in p53-deficient human colon cancer cells. MK-1775 inhibits CDC2 Y15 phosphorylation in cells, abrogates DNA damaged checkpoints induced by 5-FU treatment, and causes premature entry of mitosis determined by induction of Histone H3 phosphorylation[1]. MK-1775 abrogates the radiation-induced G₂ block in p53-defective cells but not in p53 wild-type lines[2]. The combination of gemcitabine with MK-1775 produces robust anti-tumor activity and remarkably enhances tumor regression response (4.01 fold) compared to gemcitabine treatment in p53-deficient tumors[3].

In Vivo

In vivo, MK-1775 potentiates the anti-tumor efficacy of 5-FU or its prodrug, capecitabine, at tolerable doses[1]. MK-1775 (60 mg/kg twice daily, p.o.) enhances H1299 xenograft tumor response to fractionated radiotherapy[2]. MK-1775 (30 mg/kg. p.o.) regresses tumor growth in PANC198, PANC215 and PANC185 as compared to GEM treated mice[3].

Clinical Trial
NCT Number Sponsor Condition Start Date Phase
NCT02482311 AstraZeneca Ovarian Cancer, TNBC, SCLC, Other Solid Tumours July 1, 2015 Phase 1
NCT02610075 AstraZeneca Locally Advanced Solid Tumours|Metastatic Solid Tumours|Ovarian Cancer December 1, 2015 Phase 1
NCT01748825 National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC) Neoplasms|Lymphoma November 14, 2012 Phase 1
NCT02207010 St. Joseph's Hospital and Medical Center, Phoenix|The Ben & Catherine Ivy Foundation|American Society of Clinical Oncology|Barbara Ann Karmanos Cancer Institute|Translational Genomics Research Institute Glioblastoma|GBM July 2014 Early Phase 1
NCT02511795 AstraZeneca Ovarian, Breast, and Second-Line Small Cell Lung Cancer August 6, 2015 Phase 1
NCT02593019 Samsung Medical Center Small Cell Lung Cancer December 2015 Phase 2
NCT02688907 Samsung Medical Center Small Cell Lung Cancer April 2016 Phase 2
NCT02272790 AstraZeneca Ovarian, Fallopian Tube, Peritoneal Cancer, P53 Mutation January 30, 2015 Phase 2
NCT02341456 AstraZeneca Advanced Solid Tumours January 16, 2015 Phase 1
NCT02381548 National Cancer Institute (NCI) Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive|Previously Treated Myelodysplastic Syndrome|Recurrent Adult Acute Myeloid Leukemia|Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive|Secondary Acute Myeloid Leukemia|Therapy-Related Acute Myeloid Leukemia|Untreated Adult Acute Myeloid Leukemia August 18, 2015 Phase 1
NCT02513563 H. Lee Moffitt Cancer Center and Research Institute Lung Cancer September 8, 2015 Phase 2
NCT02617277 AstraZeneca Advanced Solid Tumours December 18, 2015 Phase 1
NCT02906059 New York University School of Medicine|AstraZeneca Metastatic Colorectal Cancer September 2016 Phase 1
NCT02791919 National Cancer Institute (NCI) CNS 2a|CNS 2b|CNS 2c|CNS1|Recurrent Adult Acute Myeloid Leukemia|Recurrent Childhood Acute Myeloid Leukemia May 25, 2017 Phase 1
NCT01849146 National Cancer Institute (NCI) Adult Glioblastoma|Recurrent Glioblastoma August 19, 2013 Phase 1
NCT02087176 AstraZeneca Previously Treated Non Small Cell Lung Cancer March 2014 Phase 2
NCT03012477 Dana-Farber Cancer Institute|AstraZeneca Triple-negative Metastatic Breast Cancer January 18, 2017 Phase 2
NCT02659241 M.D. Anderson Cancer Center|AstraZeneca Ovarian Cancer|Fallopian Tube Cancer|Peritoneum Cancer February 2016 Early Phase 1
NCT01922076 National Cancer Institute (NCI) Diffuse Intrinsic Pontine Glioma|Untreated Childhood Anaplastic Astrocytoma|Untreated Childhood Anaplastic Oligoastrocytoma|Untreated Childhood Glioblastoma|Untreated Childhood Gliosarcoma September 3, 2013 Phase 1
NCT02087241 AstraZeneca Previously Untreated Stage IV Non-Squamous Non Small Cell Lung Cancer March 2014 Phase 2
NCT02585973 UNC Lineberger Comprehensive Cancer Center|AstraZeneca Carcinoma, Squamous Cell of Head and Neck February 2016 Phase 1
NCT02666950 Mayo Clinic|National Cancer Institute (NCI) Chronic Myelomonocytic Leukemia|Myelodysplastic Syndrome With Isolated Del(5q)|Myelodysplastic/Myeloproliferative Neoplasm|Previously Treated Myelodysplastic Syndrome|Recurrent Adult Acute Myeloid Leukemia|Untreated Adult Acute Myeloid Leukemia December 2016 Phase 2
NCT02448329 Samsung Medical Center Advanced Gastric Adenocarcinoma January 14, 2015 Phase 2
NCT01958658 National Cancer Institute (NCI) Stage IB Cervical Cancer|Stage IIA Cervical Cancer|Stage IIB Cervical Cancer|Stage IIIA Cervical Cancer|Stage IIIB Cervical Cancer September 5, 2013 Phase 1
NCT03028766 University of Birmingham|AstraZeneca|Cancer Research UK Hypopharynx Squamous Cell Carcinoma|Oral Cavity Squamous Cell Carcinoma|Larynx Cancer May 2017 Phase 1
NCT02508246 University of Washington|National Cancer Institute (NCI) Head and Neck Squamous Cell Carcinoma July 22, 2015 Phase 1
NCT02095132 National Cancer Institute (NCI) Childhood Central Nervous System Neoplasm|Recurrent Childhood Medulloblastoma|Recurrent Childhood Supratentorial Embryonal Tumor, Not Otherwise Specified|Recurrent Malignant Solid Neoplasm|Recurrent Neuroblastoma March 27, 2014 Phase 1|Phase 2
NCT02576444 Joseph Paul Eder|Dana-Farber Cancer Institute|Vanderbilt-Ingram Cancer Center|Yale University Cancer November 2015 Phase 2
NCT02196168 National Cancer Institute (NCI) Recurrent Hypopharyngeal Squamous Cell Carcinoma|Recurrent Laryngeal Squamous Cell Carcinoma|Recurrent Laryngeal Verrucous Carcinoma|Recurrent Lip and Oral Cavity Squamous Cell Carcinoma|Recurrent Metastatic Squamous Cell Carcinoma in the Neck With Occult Primary|Recurrent Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma|Recurrent Oral Cavity Verrucous Carcinoma|Recurrent Oropharyngeal Squamous Cell Carcinoma|Squamous Cell Carcinoma Metastatic in the Neck With Occult Primary|Stage IV Hyp March 2014 Phase 2
NCT02194829 National Cancer Institute (NCI) Metastatic Pancreatic Adenocarcinoma|Stage III Pancreatic Cancer|Stage IV Pancreatic Cancer|Unresectable Pancreatic Carcinoma July 1, 2014 Phase 1|Phase 2
NCT02937818 AstraZeneca Platinum Refractory Extensive-Stage Small Cell Lung Carcinoma November 28, 2016 Phase 2
NCT02101775 National Cancer Institute (NCI) Ovarian Brenner Tumor|Ovarian Carcinosarcoma|Ovarian Clear Cell Cystadenocarcinoma|Ovarian Endometrioid Adenocarcinoma|Ovarian Mucinous Cystadenocarcinoma|Ovarian Seromucinous Carcinoma|Ovarian Serous Cystadenocarcinoma|Ovarian Serous Surface Papillary Adenocarcinoma|Recurrent Fallopian Tube Carcinoma|Recurrent Ovarian Carcinoma|Recurrent Primary Peritoneal Carcinoma|Undifferentiated Ovarian Carcinoma July 21, 2014 Phase 2
NCT02546661 AstraZeneca Muscle Invasive Bladder Cancer October 3, 2016 Phase 1
NCT02465060 National Cancer Institute (NCI) Advanced Malignant Solid Neoplasm|Lymphoma|Recurrent Malignant Solid Neoplasm|Recurrent Plasma Cell Myeloma|Refractory Malignant Neoplasm|Refractory Plasma Cell Myeloma August 12, 2015 Phase 2
NCT02813135 Gustave Roussy, Cancer Campus, Grand Paris|National Cancer Institute, France Children, Adolescents and Young Adults With Refractory or Recurrent Malignancies June 2016 Phase 1|Phase 2
NCT01827384 National Cancer Institute (NCI) Advanced Malignant Solid Neoplasm|Recurrent Malignant Solid Neoplasm December 31, 2013 Phase 2
NCT01164995 The Netherlands Cancer Institute|Merck Sharp & Dohme Corp. Epithelial Ovarian Cancer July 2010 Phase 2
NCT01357161 Merck Sharp & Dohme Corp. Ovarian Cancer July 2011 Phase 2
NCT02037230 University of Michigan Cancer Center Adenocarcinoma of the Pancreas January 2014 Phase 1|Phase 2
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References
Preparing Stock Solutions
Concentration Volume (DMSO) Mass 1 mg 5 mg 10 mg
1 mM 1.9976 mL 9.9880 mL 19.9760 mL
5 mM 0.3995 mL 1.9976 mL 3.9952 mL
10 mM 0.1998 mL 0.9988 mL 1.9976 mL
Cell Assay
[2]

Total protein is extracted from the cell pellet using a lysis solution containing 50 mM HEPES (pH 7.9), 0.4 mol/L NaCl, and 1 mM EDTA and fortified with 10 µL/mL phosphatase inhibitor cocktail 1, 10 µL/mL phosphatase inhibitor cocktail 2, 10 µL/mL protease inhibitor, and 1% NP-40. Protein concentration of the lysates 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 blocked in 5% nonfat dry milk in Tris (20 mM)-buffered saline (150 mM, pH 7.4) with 0.1% Tween (TBS-T). Protein signals are detected by incubating the membrane in primary antibody in 5% nonfat dry milk overnight at 4°C, followed by a 45-min incubation in the appropriate peroxidase-conjugated secondary antibody. The membrane is then developed by enhanced chemiluminescence with ECL plus Western Blotting Detection Reagents on a Typhoon 9400 scanner.

Animal Administration
[2]

Tumor xenografts are produced in the leg by im inoculation of 1×106 Calu-6 cells in 10 µL. Irradiation and 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-animal irradiator consisting of two parallel-opposed 137Cs sources, at a dose rate of 5 Gy/min. Tumors are irradiated twice daily separated by 6 h. MK-1775 is given by gavage in 0.1 mL volumes 1 h before and 2 h after the first daily radiation dose.

References
M.Wt

500.6

Formula

C₂₇H₃₂N₈O₂

CAS No.

955365-80-7

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

10 mM in DMSO

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

Purity: 98.96%

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MK-1775
Cat. No.:
HY-10993
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