Adavosertib（MK-1775）

Cat. No. M2143

Synonym:

AZD1775

Size	Price	Availability
Free Sample (0.5-1 mg)	USD 0	In stock
5mg	USD 48 USD48	In stock
10mg	USD 75 USD75	In stock

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Quality Control & Documentation

Purity: 99.89%
COA
MSDS
H-NMR
HPLC

Product Information

Biological Activity

Adavosertib (AZD1775, MK-1775) is a small pyrazolacil derivative, an effective ATP competitive specific inhibitor of WEE1 kinase, with IC50 of 5.2 nM. It can inhibit G2 phase DNA damage test sites.

Product Citations

Cancer Cell. 2018 Sep 10;34(3):411-426.e19.

Identification of Therapeutic Targets in Rhabdomyosarcoma through Integrated Genomic, Epigenomic, and Proteomic Analyses.
Adavosertib（MK-1775） purchased from AbMole
Nature. 2017 Sep 7;549(7670):96-100.

Orthotopic patient-derived xenografts of paediatric solid tumours
Adavosertib（MK-1775） purchased from AbMole

Customer Product Validations & Biological Datas

	Source	Cancer Cell (2018). Figure 8. AZD1775 (Abmole Bioscience, Houston, USA)
	Method	Targeting the G2/M
	Cell Lines	RMS cell lines
	Concentrations	1 uM
	Incubation Time	24 or 48 hr
	Results	Sustained levels of GSP and AZD1775 in tumors were above those required to potentiate cytotoxic effects in culture.

	Source	Cancer Cell (2018). Figure 7. AZD1775 (Abmole Bioscience, Houston, USA)
	Method	Targeting the G2/M
	Cell Lines	RMS cell lines
	Concentrations	1 uM
	Incubation Time	24 or 48 hr
	Results	AZD1775 combined with IRN or VCR led to high rates of DNA damage (Figure 7G), suggesting that both WEE1 and HSP90 may be druggable targets in RMS.

	Source	Nature (2017). Figure 6. AZD1775 (Abmole Bioscience)
	Method	oral gavage
	Cell Lines	Athymic nude immunodeficient mice
	Concentrations	60 mg/kg
	Incubation Time	1–5 days
	Results	The mice treated with AZD1775 + VCR + IRN had a better response than those treated with VCR + IRN alone.

	Source	Nature (2017). Figure 4. AZD1775 (Abmole Bioscience)
	Method	oral gavage
	Cell Lines	Athymic nude immunodeficient mice
	Concentrations	60 mg/kg
	Incubation Time	1–5 days
	Results	Asterisk indicates those models that had a significant difference in tumour progression for the AZD1775 + IRN + VCR relative to IRN + VCR.

Protocol (for reference only)

Cell Experiment
Cell lines	WiDr and H1299 cells
Preparation method	Cell Viability Assay. Cells were seeded in 96-well plates and treated with gemcitabine for 24 h, then with MK-1775 for an additional 24 h. Cell viability was determined with a WST-8 kit using SpectraMax (Molecular Devices).
Concentrations	0, 30, 100 and 300 nM
Incubation time	24 h

Animal Experiment
Animal models	nude rats bearing WiDr Subcutaneous xenograft tumors
Formulation	0.5% methylcellulose solution
Dosages	20mg/kg
Administration	p.o.

Chemical Information

Molecular Weight	500.61
Formula	C27H32N8O2
CAS Number	955365-80-7
Solubility (25°C)	DMSO 70 mg/mL
Storage	Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month

Conversion of different model animals based on BSA (PMID: 27057123)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m²)	0.007	0.025	0.15	0.05	0.02	0.5
K_m factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B K_m
	Animal A K_m

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

References

[1] Bridges KA, et al. Clin Cancer Res. MK-1775, a novel Wee1 kinase inhibitor, radiosensitizes p53-defective human tumor cells.

[2] Rajeshkumar NV, et al. Clin Cancer Res. MK-1775, a potent Wee1 inhibitor, synergizes with gemcitabine to achieve tumor regressions, selectively in p53-deficient pancreatic cancer xenografts.

[3] Hirai H, et al. Cancer Biol Ther. MK-1775, a small molecule Wee1 inhibitor, enhances anti-tumor efficacy of various DNA-damaging agents, including 5-fluorouracil.

[4] Hirai H, et al. Mol Cancer Ther. Small-molecule inhibition of Wee1 kinase by MK-1775 selectively sensitizes p53-deficient tumor cells to DNA-damaging agents.

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