Free shipping on all orders over $ 500

Adavosertib (MK-1775)

Cat. No. M2143
Adavosertib (MK-1775) Structure
Synonym:

AZD1775

Size Price Availability Quantity
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
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
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
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

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 Km factor for a mouse and then divide by the Km 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 (Lunresertib) 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
Abmole Inhibitor Catalog




Keywords: Adavosertib (MK-1775), AZD1775 supplier, Wee1, inhibitors, activators


Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2024 AbMole BioScience. All Rights Reserved.