Introduction：Basic information about CAS 955365-80-7|Adavosertib (MK-1775), including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
| Common Name | Adavosertib (MK-1775) |
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| CAS Number | 955365-80-7 | Molecular Weight | 500.595 |
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| Density | 1.3±0.1 g/cm3 | Boiling Point | 723.8±70.0 °C at 760 mmHg |
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| Molecular Formula | C27H32N8O2 | Melting Point | / |
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| MSDS | / | Flash Point | 391.5±35.7 °C |
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Names
| Name | 1-[6-(2-hydroxypropan-2-yl)pyridin-2-yl]-6-[4-(4-methylpiperazin-1-yl)anilino]-2-prop-2-enylpyrazolo[3,4-d]pyrimidin-3-one |
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| Synonym | More Synonyms |
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Adavosertib (MK-1775) BiologicalActivity
| Description | Adavosertib (AZD-1775; MK-1775) is a potent Wee1 inhibitor with an IC50 of 5.2 nM. |
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| Related Catalog | Signaling Pathways >>Cell Cycle/DNA Damage >>Wee1Research Areas >>Cancer |
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| Target | IC50: 5.2 nM (Wee1) |
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| In Vitro | Adavosertib (MK-1775) enhances the cytotoxic effects of 5-FU in p53-deficient human colon cancer cells. Adavosertib (MK-1775) inhibits CDC2 Y15 phosphorylation in cells, abrogates DNA damaged checkpoints induced by 5-FU treatment, and causes premature entry of mitosis determined by induction of Histone H3 phosphorylation[1]. Adavosertib (MK-1775) abrogates the radiation-induced G2 block in p53-defective cells but not in p53 wild-type lines[2]. The combination of gemcitabine with Adavosertib (MK-1775) produces robust anti-tumor activity and remarkably enhances tumor regression response (4.01 fold) compared to gemcitabine treatment in p53-deficient tumors[3]. |
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| In Vivo | In vivo, Adavosertib (MK-1775) potentiates the anti-tumor efficacy of 5-FU or its prodrug, capecitabine, at tolerable doses[1]. Adavosertib (MK-1775) (60 mg/kg twice daily, p.o.) enhances H1299 xenograft tumor response to fractionated radiotherapy[2]. Adavosertib (MK-1775) (30 mg/kg. p.o.) regresses tumor growth in PANC198, PANC215 and PANC185 as compared to GEM treated mice[3]. |
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| Cell Assay | Total protein is extracted from the cell pellet using a lysis solution containing 50 mM HEPES (pH 7.9), 0.4 mol/L NaCl, and 1 mM EDTA and fortified with 10 µL/mL phosphatase inhibitor cocktail 1, 10 µL/mL phosphatase inhibitor cocktail 2, 10 µL/mL protease inhibitor, and 1% NP-40. Protein concentration of the lysates is determined by the Bio-Rad protein assay. Equal amounts of protein are separated by 12% SDS-PAGE and transferred to an Immobilon membrane. Nonspecific binding sites on the membrane are blocked in 5% nonfat dry milk in Tris (20 mM)-buffered saline (150 mM, pH 7.4) with 0.1% Tween (TBS-T). Protein signals are detected by incubating the membrane in primary antibody in 5% nonfat dry milk overnight at 4°C, followed by a 45-min incubation in the appropriate peroxidase-conjugated secondary antibody. The membrane is then developed by enhanced chemiluminescence with ECL plus Western Blotting Detection Reagents on a Typhoon 9400 scanner. |
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| Animal Admin | Tumor xenografts are produced in the leg by im inoculation of 1×106 Calu-6 cells in 10 µL. Irradiation and Adavosertib (MK-1775) treatment are started when tumors reach 8 mm diameter and continue for 5 days. Gamma-rays are delivered locally to the tumor-bearing legs of unanesthetized mice using a small-animal irradiator consisting of two parallel-opposed 137Cs sources, at a dose rate of 5 Gy/min. Tumors are irradiated twice daily separated by 6 h. Adavosertib (MK-1775) is given by gavage in 0.1 mL volumes 1 h before and 2 h after the first daily radiation dose. |
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| References | [1]. Hirai H, et al. MK-1775, a small molecule Wee1 inhibitor, enhances anti-tumor efficacy of various DNA-damaging agents, including 5-fluorouracil Cancer Biol Ther. 2010 Apr;9(7):514-22. [2]. Bridges KA, et al. MK-1775, a novel Wee1 kinase inhibitor, radiosensitizes p53-defective human tumor cells. Clin Cancer Res. 2011 Sep 1;17(17):5638-48. Epub 2011 Jul 28. [3]. Rajeshkumar NV, et al. MK-1775, a potent Wee1 inhibitor, synergizes with gemcitabine to achieve tumor regressions, selectively in p53-deficient pancreatic cancer xenografts.Clin Cancer Res. 2011 May 1;17(9):2799-806. Epub 2011 Mar 9. |
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Chemical & Physical Properties
| Density | 1.3±0.1 g/cm3 |
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| Boiling Point | 723.8±70.0 °C at 760 mmHg |
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| Molecular Formula | C27H32N8O2 |
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| Molecular Weight | 500.595 |
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| Flash Point | 391.5±35.7 °C |
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| Exact Mass | 500.264832 |
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| PSA | 104.34000 |
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| LogP | 0.50 |
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| Vapour Pressure | 0.0±2.5 mmHg at 25°C |
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| Index of Refraction | 1.655 |
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| InChIKey | BKWJAKQVGHWELA-UHFFFAOYSA-N |
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| SMILES | C=CCn1c(=O)c2cnc(Nc3ccc(N4CCN(C)CC4)cc3)nc2n1-c1cccc(C(C)(C)O)n1 |
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Safety Information
Synonyms
| 2-allyl-1,8-dimethoxy-9,10-anthraquinone |
| 3H-Pyrazolo[3,4-d]pyrimidin-3-one, 1,2-dihydro-1-[6-(1-hydroxy-1-methylethyl)-2-pyridinyl]-6-[[4-(4-methyl-1-piperazinyl)phenyl]amino]-2-(2-propen-1-yl)- |
| 2-allyl-1-[6-(1-hydroxy-1-methylethyl)pyridin-2-yl]-6-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-one |
| 2-Allyl-1-[6-(2-hydroxy-2-propanyl)-2-pyridinyl]-6-{[4-(4-methyl-1-piperazinyl)phenyl]amino}-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-one |
| 9,10-Anthracenedione,1,8-dimethoxy-2-(2-propenyl) |
| 2-allyl-1,8-dimethoxyanthracene-9,10-dione |
| MK-1775 |
| MK1775 |
| AZD1775 |
