Adavosertib (MK-1775)

Cat. No. M2143

Synonym:

AZD1775

Size	Price	Availability
Free Sample (0.5-1 mg)	USD 0	In stock
10mM*1mL in DMSO	USD 45 USD45	In stock
5mg	USD 40 USD40	In stock
10mg	USD 65 USD65	In stock
25mg	USD 75 USD75	In stock
50mg	USD 95 USD95	In stock
500mg	USD 285 USD285	In stock

Free Delivery on orders over USD 500 Bulk Inquiry?

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. MK-1775 (Adavosertib) inhibits phosphorylation of CDC2 at Tyr15 (CDC2Y15), a direct substrate of Wee1 kinase in cells.

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 90 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.

Related Wee1 Products
WEE1-IN-5 WEE1-IN-5 is a potent WEE1 inhibitor with an IC50 value of 0.8 nM. WEE1-IN-5 inhibits phospho-CDC2. WEE1-IN-5 abrogates the G2 check point, increasing sensitivity to DNA damaging agents in cancer cells.
WEE1-IN-4 WEE1-IN-4 is a potent checkpoint Wee1 kinase inhibitor with an IC50 of 0.011 μM.
Pomalidomide-C3-adavosertib Pomalidomide-C3-adavosertib is a rapid and selective Wee1 degrader (IC50=3.58 nM). Pomalidomide-C3-adavosertib shows anti-cancer cell proliferation activity, and induces apoptosis.
PD0166285 dihydrochloride PD0166285 dihydrochloride, a substrate of P-gp, is a WEE1 inhibitor and a weak Myt1 inhibitor with IC50 values of 24 and 72 nM, respectively. PD0166285 dihydrochloride exhibits an IC50 of 3.433 μM for Chk1.
RP-6306 RP-6306 is the first-in-class, highly potent and selective PKMYT1 inhibitor that preferentially kills tumor cells overexpressing CCNE1 and was shown to inhibit the growth of a broad range of CCNE1-amplified tumors in xenograft/PDX preclinical models, both as a single agent and in combination therapy settings.

Catalog

By Signaling Pathways

By Product Type

Signaling Pathways