Adavosertib (MK-1775)

Catalog No.S1525 Batch:S152510

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Technical Data

Formula

C27H32N8O2
Molecular Weight 500.6 CAS No. 955365-80-7
Solubility (25°C)* In vitro DMSO 100 mg/mL (199.76 mM)
Water Insoluble
Ethanol Insoluble
In vivo (Add solvents to the product individually and in order)
Clear solution
5%DMSO 40%PEG 300 5%Tween80 50% ddH2O
5.0mg/ml Taking the 1 mL working solution as an example, add 50 μL of 100 mg/mL clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify; add 50 μL of Tween-80 to the above system, mix evenly to clarify; Then continue to add 500 μL ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description Adavosertib (MK-1775, AZD1775) is a potent and selective Wee1 inhibitor with IC50 of 5.2 nM in a cell-free assay; hinders G2 DNA damage checkpoint. Phase 2.
Targets
Wee1 [1]
(Cell-free assay)
5.2 nM
In vitro

MK-1775 inhibits Wee1 kinase in an ATP-competitive manner. Compared to Wee1, MK-1775 displays 2- to 3-fold less potency against Yes with IC50 of 14 nM, 10-fold less potency against seven other kinases with >80% inhibition at 1 μM, and >100-fold selectivity over human Myt 1, another kinase that inhibits cyclin-dependent kinase 1 (CDC2) by phosphorylation at an alternative site (Thr14). By abrogating the DNA damage checkpoint via blockade of Wee1 activity in WiDr cells bearing mutated p53, MK-1775 treatment inhibits the basal phosphorylation of CDC2 at Tyr15 (CDC2Y15) with EC50 of 49 nM, and suppresses induced phosphorylation of CDC2 and cell cycle arrest in a dose-dependent manner, with EC50 of 82 nM and 81 nM, 180 nM and 163 nM, as well as 159 nM and 160 nM, respectively. MK-1775 treatment alone at 30-100 nM has no significant antiproliferative effect in WiDr and H1299 cells, whereas MK-1775 at 300 nM, sufficient to inhibit Wee1 by >80%, displays moderate but significant antiproliferative effects by 34.1% in WiDr cells and 28.4% in H1299 cells. [1]
In vivo

MK-1775 treatment alone at ~20 mg/kg displays minimal antitumor effects against WiDr xenografts in rats with T/C of 69% at day 3. Antitumor efficacy by MK-1775 alone in the nude rat HeLa-luc and TOV21G-shp53 xenograft models is also moderate. [1]
Features The first reported Wee1 inhibitor.

Protocol (from reference)

Kinase Assay:

[1]
  • In vitro kinase assays

    Recombinant human Wee1 is used. Kinase reaction is conducted with 10 μM ATP, 1.0 μCi of [γ-33P]ATP, and 2.5 μg of poly(Lys, Tyr) as a substrate in the presence of increasing concentrations of MK-1775 at 30°C for 30 minutes. Radioactivity incorporated into the substrate is trapped on MultiScreen-PH plates and is counted on a liquid scintillation counter.
Cell Assay:

[1]
  • Cell lines

    WiDr, NCI-H1299, TOV21G, and HeLa

  • Concentrations

    Dissolved in DMSO, final concentrations ~10 μM

  • Incubation Time

    24 hours

  • Method

    Cells are treated for 24 hours, then with MK-1775 for an additional 24 hours. Cell viability is determined with a WST-8 kit using SpectraMax. Cellular caspase-3/7 activities are determined with a Caspase-3/7 Glo kit.
Animal Study:

[1]
  • Animal Models

    Immunodeficient nude rats (F344/NJcl-rnu) bearing WiDr, HeLa-luc, or TOV21G-shp53 tumors

  • Dosages

    ~20 mg/kg/day

  • Administration

    Orally

Customer Product Validation

Data from [Data independently produced by J Hematol Oncol, 2014, 7:53]

Data from [Data independently produced by Oncol Rep, 2014, 32(5), 1991-8]

Data from [Data independently produced by Endocrinology, 2013, 154(9), 3219-27]

Data from [Data independently produced by PLoS One, 2013, 8(3), e57523]

Selleck's Adavosertib (MK-1775) has been cited by 248 publications

Defining the KRAS- and ERK-dependent transcriptome in KRAS-mutant cancers [ Science, 2024, 384(6700):eadk0775] PubMed: 38843331
Heterogeneity-driven phenotypic plasticity and treatment response in branched-organoid models of pancreatic ductal adenocarcinoma [ Nat Biomed Eng, 2024, 10.1038/s41551-024-01273-9] PubMed: 39658630
Comprehensive multi-omics analysis reveals WEE1 as a synergistic lethal target with hyperthermia through CDK1 super-activation [ Nat Commun, 2024, 15(1):2089] PubMed: 38453961
ATR limits Rad18-mediated PCNA monoubiquitination to preserve replication fork and telomerase-independent telomere stability [ EMBO J, 2024, 43(7):1301-1324] PubMed: 38467834
ATR, CHK1 and WEE1 inhibitors cause homologous recombination repair deficiency to induce synthetic lethality with PARP inhibitors [ Br J Cancer, 2024, 10.1038/s41416-024-02745-0] PubMed: 38965423
GCN2 is a determinant of the response to WEE1 kinase inhibition in small-cell lung cancer [ Cell Rep, 2024, 43(8):114606] PubMed: 39120974
G2 arrest primes hematopoietic stem cells for megakaryopoiesis [ Cell Rep, 2024, 43(7):114388] PubMed: 38935497
The Golgi checkpoint: Golgi unlinking during G2 is necessary for spindle formation and cytokinesis [ Life Sci Alliance, 2024, 7(5)e202302469] PubMed: 38479814
Afatinib or Bevacizumab in combination with Osimertinib efficiently control tumor development in orthotopic murine models of non-small lung cancer [ PLoS One, 2024, 19(6):e0304914] PubMed: 38935790
The polymeric fluoropyrimidine CF10 overcomes limitations of 5-FU in pancreatic ductal adenocarcinoma cells through increased replication stress [ Cancer Biol Ther, 2024, 25(1):2421584] PubMed: 39513592

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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