Adavosertib (AZD-1775; MK-1775) is a potent Wee1 inhibitor with an IC50 of 5.2 nM.
For research use only. We do not sell to patients.
Adavosertib Chemical Structure
CAS No. : 955365-80-7
This product is a controlled substance and not for sale in your territory.
Based on 40 publication(s) in Google Scholar
Adavosertib purchased from MedChemExpress. Usage Cited in:
J Hematol Oncol. 2018 Aug 1;11(1):99.
[Abstract]
Representative immunoblots showing the expression of key proteins of the WEE1 pathway after treatment with AZD-1775 (IC50 for each cell line) for 24 h of the indicated cells lines. β-actin is used for loading normalization.
Adavosertib purchased from MedChemExpress. Usage Cited in:
Cancer Res. 2017 Sep 1;77(17):4663-4672.
[Abstract]
Isogenic A549 or H2030 cells expressing full-length LKB1 or kinase-dead LKB1(KDLKB1) are treated with 1 μM AZD1775 or vehicle (DMSO) for 24 hours. Protein lysates are immunoblotted with the indicated antibodies. Actin was used as a loading control.
Adavosertib purchased from MedChemExpress. Usage Cited in:
Scienze biomediche. University of Bologna. 2016 Apr.
In the blots B-/T-ALL cell lines are incubated for 24 hours with MK-1775 (IC50 value). The homogeneity of the protein loaded (40 μg) is determined using an internal control (β-actin).
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Description
Adavosertib (AZD-1775; MK-1775) is a potent Wee1 inhibitor with an IC50 of 5.2 nM.
IC50 & Target
IC50: 5.2 nM (Wee1)
In Vitro
Adavosertib (MK-1775) enhances the cytotoxic effects of 5-FU in p53-deficient human colon cancer cells. Adavosertib (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]. Adavosertib (MK-1775) abrogates the radiation-induced G2 block in p53-defective cells but not in p53 wild-type lines[2]. The combination of NSC 613327 with Adavosertib (MK-1775) produces robust anti-tumor activity and remarkably enhances tumor regression response (4.01 fold) compared to NSC 613327 treatment in p53-deficient tumors[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Adavosertib Related Antibodies
In Vivo
In vivo, Adavosertib (MK-1775) potentiates 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 fractionated radiotherapy[2]. Adavosertib (MK-1775) (30 mg/kg. p.o.) regresses tumor growth in PANC198, PANC215 and PANC185 as compared to GEM treated mice[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Room temperature in continental US; may vary elsewhere.
Storage
Powder
-20°C
3 years
4°C
2 years
In solvent
-80°C
1 year
-20°C
6 months
Solvent & Solubility
In Vitro:
DMSO : 125 mg/mL (249.70 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Preparing Stock Solutions
ConcentrationSolventMass
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
View the Complete Stock Solution Preparation Table
*Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles. Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.
For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day. The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Protocol 1
Add each solvent one by one: 5% DMSO 40% PEG300 5% Tween-80 50% Saline
This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (20.8 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 3
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (20.8 mg/mL) to 900 μLCorn oil, and mix evenly.
For the following dissolution methods, please prepare the working solution directly.
It is recommended to prepare fresh solutions and use them promptly within a short period of time. The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution.
If precipitation or phase separation occurs during preparation,
heat and/or sonication can be used to aid dissolution.
Protocol 1
Add each solvent one by one: 0.5% Methylcellulose/saline water
Solubility: 5 mg/mL (9.99 mM); Suspension solution; Need ultrasonic
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
Dosage
mg/kg
Animal weight (per animal)
g
Dosing volume (per animal)
μL
Number of animals
Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO+
%
+
%
Tween-80
+
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO,
. All of co-solvents are available by MedChemExpress (MCE).
, Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration:
mg/mL
Method for preparing stock solution:
mg
drug dissolved in
μL
DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take
μL DMSO stock solution, add
μL .
μL , mix evenly, next add
μL Tween 80, mix evenly, then add
μL Saline.
Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution
If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
[1]. Hirai H, et al. MK-1775, a 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.
[Content Brief]
[2]. Bridges KA, et al. MK-1775, a novel Wee1 kinase inhibitor, radiosensitizes p53-defective human tumor cells. Clin Cancer Res. 2011 Sep 1;17(17):5638-48. Epub 2011 Jul 28.
[Content Brief]
[3]. Rajeshkumar NV, et al. MK-1775, a potent Wee1 inhibitor, synergizes with NSC 613327 to achieve tumor regressions, selectively in p53-deficient pancreatic cancer xenografts.Clin Cancer Res. 2011 May 1;17(9):2799-806. Epub 2011 Mar 9.
[Content Brief]
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.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration
[2]
Tumor xenografts are produced in the leg by im inoculation of 1×106 Calu-6 cells in 10 µL. Irradiation and Adavosertib (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. Adavosertib (MK-1775) is given by gavage in 0.1 mL volumes 1 h before and 2 h after the first daily radiation dose.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
References
[1]. Hirai H, et al. MK-1775, a 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.
[Content Brief]
[2]. Bridges KA, et al. MK-1775, a novel Wee1 kinase inhibitor, radiosensitizes p53-defective human tumor cells. Clin Cancer Res. 2011 Sep 1;17(17):5638-48. Epub 2011 Jul 28.
[Content Brief]
[3]. Rajeshkumar NV, et al. MK-1775, a potent Wee1 inhibitor, synergizes with NSC 613327 to achieve tumor regressions, selectively in p53-deficient pancreatic cancer xenografts.Clin Cancer Res. 2011 May 1;17(9):2799-806. Epub 2011 Mar 9.
[Content Brief]
[1]. Hirai H, et al. MK-1775, a 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 Sep 1;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 in p53-deficient pancreatic cancer xenografts.Clin Cancer Res. 2011 May 1;17(9):2799-806. Epub 2011 Mar 9.
Complete Stock Solution Preparation Table
*Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles. Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.
Optional Solvent
ConcentrationSolventMass
1 mg
5 mg
10 mg
25 mg
DMSO
1 mM
1.9976 mL
9.9880 mL
19.9760 mL
49.9401 mL
5 mM
0.3995 mL
1.9976 mL
3.9952 mL
9.9880 mL
10 mM
0.1998 mL
0.9988 mL
1.9976 mL
4.9940 mL
15 mM
0.1332 mL
0.6659 mL
1.3317 mL
3.3293 mL
20 mM
0.0999 mL
0.4994 mL
0.9988 mL
2.4970 mL
25 mM
0.0799 mL
0.3995 mL
0.7990 mL
1.9976 mL
30 mM
0.0666 mL
0.3329 mL
0.6659 mL
1.6647 mL
40 mM
0.0499 mL
0.2497 mL
0.4994 mL
1.2485 mL
50 mM
0.0400 mL
0.1998 mL
0.3995 mL
0.9988 mL
60 mM
0.0333 mL
0.1665 mL
0.3329 mL
0.8323 mL
80 mM
0.0250 mL
0.1249 mL
0.2497 mL
0.6243 mL
100 mM
0.0200 mL
0.0999 mL
0.1998 mL
0.4994 mL
Adavosertib Related Classifications
Help & FAQs
Do most proteins show cross-species activity?
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.
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