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Submit ReviewAdavosertib
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)
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 |
| InChI Key | BKWJAKQVGHWELA-UHFFFAOYSA-N |
| 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 | |
|---|---|---|---|
| Solubility | |||
| 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.
| 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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Product Datasheets for Adavosertib
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
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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
This product guide provides a review of the cell cycle and DNA damage research area and lists over 150 products, including research tools for:
- Cell Cycle and Mitosis
- DNA Damage Repair
- Targeted Protein Degradation
- Ubiquitin Proteasome Pathway
- Chemotherapy Targets
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.