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Description: Potent and selective Wee1 inhibitor
Alternative Names: AZD 1775,MK 1775
Chemical Name: 1,2-Dihydro-1-[6-(1-hydroxy-1-methylethyl)-2-pyridinyl]-6-[[4-(4-methyl-1-piperazinyl)phenyl]amino]-2-(2-propen-1-yl)-3H-pyrazolo[3,4-d]pyrimidin-3-one
Purity: ≥98% (HPLC)
Literature (2)

Biological Activity for Adavosertib

Adavosertib is a potent and selective Wee1 inhibitor (IC50 = 5.2 nM). Blocks CDC2Y15 phosphorylation and Gemcitabine (Cat. No. 3259)-induced DNA damage checkpoint, leading to premature mitotic entry and apoptosis in p53-deficient tumor cell lines. Adavosertib synergizes with gemcitabine to achieve tumor regression in p53-deficient pancreatic cancer xenografts, with Olaparib (Cat. No. 7579) to inhibit SCLC xenograft tumor growth, and inhibits SCLC tumor growth in vivo. Adavosertib also potentiates the cytotoxic effects of Pemetrexed (Cat. No. 6185), Doxorubicin (Cat. No. 2252), Camptothecin (Cat. No. 1100) and Mitomycin C (Cat. No. 3258) in vitro.

Compound Libraries for Adavosertib

Adavosertib is also offered as part of the Tocriscreen Kinase Inhibitor Library. Find out more about compound libraries available from Tocris.

Technical Data for Adavosertib

M. Wt 500.6
Formula C27H32N8O2
Storage Store at -20°C
Purity ≥98% (HPLC)
CAS Number 955365-80-7
PubChem ID 24856436
Smiles O=C1C2=CN=C(N=C2N(C=3N=C(C=CC3)C(O)(C)C)N1CC=C)NC4=CC=C(C=C4)N5CCN(C)CC5

The technical data provided above is for guidance only. For batch specific data refer to the Certificate of Analysis.

Tocris products are intended for laboratory research use only, unless stated otherwise.

Solubility Data for Adavosertib

Solvent Max Conc. mg/mL Max Conc. mM
DMSO 50.06 100

Preparing Stock Solutions for Adavosertib

The following data is based on the product molecular weight 500.6. Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Select a batch to recalculate based on the batch molecular weight:
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 2 mL 9.99 mL 19.98 mL
5 mM 0.4 mL 2 mL 4 mL
10 mM 0.2 mL 1 mL 2 mL
50 mM 0.04 mL 0.2 mL 0.4 mL

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References for Adavosertib

References are publications that support the biological activity of the product.

Hirai et al (2009) Small-molecule inhibition of Wee1 kinase by MK-1775 selectively sensitizes p53-deficient tumor cells to DNA-damaging agents. Mol.Cancer Ther. 8 2992 PMID: 19887545

Hirai et al (2010) MK-1775, a small molecule Wee1 inhibitor, enhances anti-tumor efficacy of various DNA-damaging agents, including 5-fluorouracil. Cancer Biol.Ther. 9 514 PMID: 20107315

Rajeshkumar et al (2011) MK-1775, a potent Wee1 inhibitor, synergizes with gemcitabine to achieve tumor regressions, selectively in p53-deficient pancreatic cancer xenografts. Clin.Cancer Res. 17 2799 PMID: 21389100

Lallo et al (2018) The combination of the PARP inhibitor olaparib and the WEE1 inhibitor AZD1775 as a new therapeutic option for small cell lung cancer. Clin.Cancer Res. 24 5153 PMID: 29941481

If you know of a relevant reference for Adavosertib, please let us know.

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Citations for Adavosertib

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Literature in this Area

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Cell Cycle and DNA Damage Research Product Guide

Cell Cycle and DNA Damage Research Product Guide

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Cell Cycle & DNA Damage Repair Poster

In normal cells, each stage of the cell cycle is tightly regulated, however in cancer cells many genes and proteins that are involved in the regulation of the cell cycle are mutated or over expressed. This poster summarizes the stages of the cell cycle and DNA repair. It also highlights strategies for enhancing replicative stress in cancer cells to force mitotic catastrophe and cell death.