Adavosertib (MK-1775)

For research use only. Not for use in humans.

Catalog No.S1525

111 publications

Adavosertib (MK-1775) Chemical Structure

Molecular Weight(MW): 500.6

MK-1775 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.

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Selleck's Adavosertib (MK-1775) has been cited by 111 publications

Purity & Quality Control

Choose Selective Wee1 Inhibitors

Biological Activity

Description MK-1775 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.
Features The first reported Wee1 inhibitor.
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 gemcitabine-, carboplatin- or cisplatin-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]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
ASPC-1 NUnzVoNlT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGLHXZlKSzVyPUGzMlIhyrFiMT6xJO69VQ>? Mm\NNlU1PTh7NUS=
BxPC-3 MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFLKe4tKSzVyPUCuPEDDuSByLkCzJO69VQ>? NYX2fFBrOjV2NUi5OVQ>
CFPAC-1 Mn3IS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NY\CRXZ{UUN3ME2zMlMhyrFiMD6yJO69VQ>? NXvKdZJLOjV2NUi5OVQ>
HPAC MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHHvdItKSzVyPUCuOUDDuSByLkCxJO69VQ>? Ml7SNlU1PTh7NUS=
MIAPaCa-2 MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVPJR|UxRTBwNTFCtUAxNjB3IN88US=> NEjkXWczPTR3OEm1OC=>
PANC-1 NULocWxbT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnrVTWM2OD1zMD62JOKyKDFwMTFOwG0> MXGyOVQ2QDl3NB?=
SK-N-BE (2) MV3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M17pUWlEPTB;Mj605qCKyrIkgJmwMlMh|ryP NIjpb4czPTNyOEmxOi=>
SK-N-BE (2), PAN→MK NYKyNmZzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2HxOGlEPTB;Mk[uOwKBkcLz4pEJPU43KM7:TR?= M{DRelI2OzB6OUG2
SK-N-BE (2), MK→PAN M{jie2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NG\tb2RKSzVyPUKuOQKBkcLz4pEJNE4{KM7:TR?= NVrZc4d4OjV|MEi5NVY>
SK-N-AS NGHNOHRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWHJR|UxRTBwNUFihKnDueLCiUCuNFIh|ryP MoD4NlU{ODh7MU[=
SK-N-DZ MoP1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NI\tcZdKSzVyPUCuN|bjiIoEsfMAjVAvODFizszN MkDmNlU{ODh7MU[=
SK-N-AS NX;xfnJjSXCxcITvd4l{KEG|c3H5 M4fMS|UxOCCwTR?= NGHKd481QCCq MV3pcoR2[2W|IHPlcIwh[XCxcITvd4l{ MknxNlU{ODh7MU[=
SK-N-DZ NIHK[YtCeG:ydH;zbZMhSXO|YYm= NHvNdXY2ODBibl2= M32xXVQ5KGh? M37LWYlv\HWlZYOgZ4VtdCCjcH;weI9{cXN? MVKyOVMxQDlzNh?=
THP-1 NHXy[GdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkDYNVI2NzJ3MD:1NFAhdk1? NYjpbHp5PDhiaB?= NFLTUZpqdmO{ZXHz[ZMh[2WubDDk[YF1cCCrbjDhJINwdmOnboTyZZRqd25vZHXw[Y5l\W62IH3hco5meg>? M3TPSFI2ODh2NkG0
MV4-11 NV7sZYJ4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NX\Q[HpoOTJ3L{K1NE82ODBibl2= NXHD[nVxPDhiaB?= M1:0SIlv[3KnYYPld{Bk\WyuIHTlZZRpKGmwIHGgZ49v[2WwdILheIlwdi2mZYDlcoRmdnRibXHucoVz MknKNlUxQDR4MUS=
U937 MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3fxflEzPS9{NUCvOVAxKG6P NXLjTm82PDhiaB?= MYHpcoNz\WG|ZYOgZ4VtdCCmZXH0bEBqdiCjIHPvcoNmdnS{YYTpc44u\GWyZX7k[Y51KG2jbn7ldi=> NXm3UGIyOjVyOES2NVQ>
HL-60 NWXwO2J7T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXKxNlUwOjVyL{WwNEBvVQ>? MnT2OFghcA>? MkLQbY5kemWjc3XzJINmdGxiZHXheIghcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI> MnXWNlUxQDR4MUS=
OCI-AML3 MnHtS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUGxV|hHOTJ3L{K1NE82ODBibl2= M1;JO|Q5KGh? MoTrbY5kemWjc3XzJINmdGxiZHXheIghcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI> NV2wOld{OjVyOES2NVQ>
MOLM-13 NHHTRnBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NW\EOZFUOTJ3L{K1NE82ODBibl2= Mmm2OFghcA>? M373NYlv[3KnYYPld{Bk\WyuIHTlZZRpKGmwIHGgZ49v[2WwdILheIlwdi2mZYDlcoRmdnRibXHucoVz NXLmNWdUOjVyOES2NVQ>
CMK NYe2SGpKS2WubDDWbYFjcWyrdImgRZN{[Xl? NEG1WHQyOC1zMECwNEBvVQ>? Mk\5O|IhcA>? M2LS[pJm\HWlZYOgZ4VtdCC4aXHsbYJqfHliaX6gZUBkd26lZX70doF1cW:wLXTldIVv\GWwdDDtZY5v\XJ? NW\EVGVGOjR7NkKzN|E>
CMY MYjD[YxtKF[rYXLpcIl1gSCDc4PhfS=> M4jpZlExNTFyMECwJI5O MUC3NkBp M2\NOpJm\HWlZYOgZ4VtdCC4aXHsbYJqfHliaX6gZUBkd26lZX70doF1cW:wLXTldIVv\GWwdDDtZY5v\XJ? M4G5N|I1QTZ{M{Ox
Dayo MnrYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoLETWM2OD1zNUCgcm0> NXvIeFVVOjR4NkG5NVA>
UW228 MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIfk[INKSzVyPUKzNkBvVQ>? M3\K[FI1PjZzOUGw
IST-MES1 NWnjXY5vS2WubDDWbYFjcWyrdImgRZN{[Xl? M3S3N|E2OC9{NUCgcm0> NVj6fIw{PzJiaB?= NX3KOoZQ\W6qYX7j[ZMhfGinIHPpd5Bt[XSrbjDjfZRwfG:6aXOg[YZn\WO2IHnuJIEh[2:wY3XueJJifGmxbj3k[ZBmdmSnboSgcYFvdmW{ MUmyOFM3PTd6Mh?=
IST-MES2 NFviOZdE\WyuIG\pZYJqdGm2eTDBd5NigQ>? NFPKUGsyPTBxMkWwJI5O M3fqPFczKGh? M2TXSYVvcGGwY3XzJJRp\SClaYPwcIF1cW5iY4n0c5RwgGmlIHXm[oVkfCCrbjDhJINwdmOnboTyZZRqd25vZHXw[Y5l\W62IH3hco5meg>? M1POWFI1OzZ3N{iy
REN MXfD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NYjtfoE5OTVyL{K1NEBvVQ>? M2LCTFczKGh? MYjlcohidmOnczD0bIUh[2m|cHzheIlvKGO7dH;0c5hq[yCnZn\lZ5QhcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI> NITqb5IzPDN4NUe4Ni=>
NCI-H2452 M4\VR2NmdGxiVnnhZoltcXS7IFHzd4F6 NUnvVXZ{OTVyL{K1NEBvVQ>? NYSwT2lnPzJiaB?= M3LoeoVvcGGwY3XzJJRp\SClaYPwcIF1cW5iY4n0c5RwgGmlIHXm[oVkfCCrbjDhJINwdmOnboTyZZRqd25vZHXw[Y5l\W62IH3hco5meg>? NXK1bVViOjR|NkW3PFI>
MSTO-211H MXrD[YxtKF[rYXLpcIl1gSCDc4PhfS=> MkDnNVUxNzJ3MDDuUS=> MYS3NkBp NXPUV2Vk\W6qYX7j[ZMhfGinIHPpd5Bt[XSrbjDjfZRwfG:6aXOg[YZn\WO2IHnuJIEh[2:wY3XueJJifGmxbj3k[ZBmdmSnboSgcYFvdmW{ NX3ud2l2OjR|NkW3PFI>
NCI-H2052 M4nOTGNmdGxiVnnhZoltcXS7IFHzd4F6 MnXFNVUxNzJ3MDDuUS=> MYe3NkBp MVLlcohidmOnczD0bIUh[2m|cHzheIlvKGO7dH;0c5hq[yCnZn\lZ5QhcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI> NVXiN|I{OjR|NkW3PFI>
WEE1 NVTRVZdTT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUn6Z5VIUUN3ME21MlIhdk1? M37hbFI{Pjl7NkW1
CDC2 NYSxSlRZT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWTheol5UUN3MP-8olExODBibl2= NFjjOmszOzZ7OU[1OS=>
CDK7 Ml22S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M13vfWlEPTExvK6xNFAxKG6P NF;iVnEzOzZ7OU[1OS=>
MYT1 MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVTFPGhMUUN3ME21N|Ahdk1? NILSd4gzOzZ7OU[1OS=>
T98G  MU\BdI9xfG:|aYOgRZN{[Xl? MXexNFAwOjVyIH7N NXHyeoxKPiCq NUfQWnd[\W6qYX7j[ZMhemGmaXH0bY9vNWmwZIXj[YQh[2WubDDrbYxtcW6p M3rRcVIyQTl{N{mz
A549 NHfn[nZCeG:ydH;zbZMhSXO|YYm= M37u[lIxOCCwTR?= MlPYNUBp NGXNeYJz[WSrb4PlcpNqfGm8ZYOgUnNEVENiY3XscJMhcW5iYTDwOVMu\GWyZX7k[Y51KG2jbn7ldi=> M1TmOlIyPzl7MEOz
H460 NYW3eYtPSXCxcITvd4l{KEG|c3H5 NEjOeIczODBibl2= Mn7HNUBp M2HhTJJi\Gmxc3Xud4l1cXqnczDOV2NNSyClZXzsd{BqdiCjIIC1N{1l\XCnbnTlcpQhdWGwbnXy MmLqNlE4QTlyM{O=
H1299 MnPHRZBweHSxc3nzJGF{e2G7 MkXHNlAxKG6P M2T3UVEhcA>? NVvafog2emGmaX;z[Y5{cXSrenXzJG5US0yFIHPlcIx{KGmwIHGgdFU{NWSncHXu[IVvfCCvYX7u[ZI> MUCyNVc6QTB|Mx?=
Calu-6  NGLVN|NCeG:ydH;zbZMhSXO|YYm= NUTRN4V6OjByIH7N NGH5cFIyKGh? MX\yZYRqd3OnboPpeIl7\XNiTmPDUGMh[2WubIOgbY4h[SCyNUOt[IVx\W6mZX70JI1idm6nch?= MknNNlE4QTlyM{O=
WiDr MlTaT4lv[XOnIFHzd4F6ew>? MnzwNVAuOTByMECgcm0> NF:wSIY5KGh? NE\Vc5FqdmirYnn0d{BxcG:|cHjvdplt[XSrb36gc4YhS0SFMjDheEBVgXJzNTD3bZRpKGGwIFXDOVDDqH[jbIXlJI9nKDh3IH7tc4wwVCCycnX0doVifGWmIIfpeIgh\2WvY3n0ZYJqdmV? MXSxPVg5PzV2NR?=

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
p-Cdk1(Y15) / Cdk1; 

PubMed: 25609063     


The impact of a 24 hour pre-treatment of MK-1775 on p-Cdk1 was assessed by western blotting. Because of low basal phosphorylation, GBM22 was irradiated (RT) with 10 Gy.

p-KAP1(S824) / p-Chk2(T68) / p-Chk1(S345); 

PubMed: 25609063     


Western blot evaluation of GBM6 and GBM22 short-term explant cultures 24 hours after treatment with either MK-1775 or TMZ or the combination. 

PARP / CF-PARP / pH3(S10) / p-CDC25c(S216) / p-CDK2(Y15); 

PubMed: 25458954     


Pancreatic cancer cells were treated with vehicle control or 500 nM MK-1775 for 48 h. Whole cell lysates were subjected to Western blotting and probed with anti-PARP, -p-H3, -γH2AX, -p-CHK1, -CHK1, -p-CDC25C, -p-CDK1, - CDK1, -p-CDK2, -CDK2, or -β-actin antibody.

WEE1; 

PubMed: 27616351     


MIA PaCa2, PANC-1, Hs 766T, Capan-1 and PL11 cells were treated with MK-1775 (400 nM/L) and/or MMC (150 nM/L) for 24 hours. Whole cell lysates were prepared using RIPA and western blot was performed to assess the protein expression of WEE1 (90 kDa), pCDK1(y15) (34 kDa), CDK1 (34 kDa) and GAPDH (36 kDa) as loading control. 

25609063 25458954 27616351
Immunofluorescence
tubulin / p-HH3(S10); 

PubMed: 30755439     


FaDu and UNC7 cells were treated with adavosertib (500 nM), alisertib (250 nM), or adavosertib + alisertib for 24 hours and followed by immunofluorescent staining with anti-tubulin (Green) and anti-pHH3 (S10; Red). Nucleus was stained with DAPI. (A) Representative images of mitotic cells were captured by confocal microscopy. Scale bar: 10 µm.

γH2AX; 

PubMed: 25609063     


A) γH2AX foci formation in GBM6 and GBM22 were assessed 24 h after a single treatment of 300 nM MK-1775. 

Cleaved caspase-3 / pH3; 

PubMed: 27616351     


MIA PaCa2 cells were treated and dual stained with pH3 to observe mitotic entry; and cleaved caspase 3 (CL-CSP3) to observe caspase 3 activity.

30755439 25609063 27616351
Growth inhibition assay
Cell viability; 

PubMed: 25458954     


Pancreatic cancer cell lines were cultured in 96-well plates at 37℃ for 48 h in complete medium with variable concentrations of MK-1775 and viable cell numbers were determined using MTT reagent and a microplate reader. The data are presented as means ± standard errors from at least 3 independent experiments.

IC50; 

PubMed: 25084614     


AML cell lines were cultured for 72 h in complete medium with variable concentrations of MK-1775 (MK) and viable cell numbers were determined using MTT assays. IC50 values were calculated as drug concentration necessary to inhibit 50% growth compared to untreated control cells.

25458954 25084614
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]

Protocol

Kinase Assay:

[1]

- Collapse

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 Research:

[1]

- Collapse
  • Cell lines: WiDr, NCI-H1299, TOV21G, and HeLa
  • Concentrations: Dissolved in DMSO, final concentrations ~10 μM
  • Incubation Time: 24 hours
  • Method:

    Cells are treated with or without gemcitabine 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.


    (Only for Reference)
Animal Research:

[1]

- Collapse
  • Animal Models: Immunodeficient nude rats (F344/NJcl-rnu) bearing WiDr, HeLa-luc, or TOV21G-shp53 tumors
  • Formulation: Prepared in a vehicle of 0.5% methylcellulose solution
  • Dosages: ~20 mg/kg/day
  • Administration: Orally
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 80 mg/mL (159.8 mM)
Ethanol 10 mg/mL (19.97 mM)
Water 0.0001 mg/mL (0.0 mM)
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
2% DMSO+30% PEG 300+5% Tween 80+ddH2O
For best results, use promptly after mixing.
5mg/mL

* 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.

Chemical Information

Molecular Weight 500.6
Formula

C27H32N8O2

CAS No. 955365-80-7
Storage powder
in solvent
Synonyms N/A
Smiles CN1CCN(CC1)C2=CC=C(NC3=NC4=C(C=N3)C(=O)N(CC=C)N4C5=NC(=CC=C5)C(C)(C)O)C=C2

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

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Frequently Asked Questions

  • Question 1:

    How to prepare MK1775 methylcellulose solution? and how to prepare methylcellulose itself? Once make the MK1775 methylcellulose solution, how should i keep it?

  • Answer:

    MK1775 in 0.5% methylcellulose is a suspension or emulsion, and it is ok to treat mice orally. It is recommended to dissolve methylcellulose in saline. It will take some time to dissolve methylcellulose, and you can vortex it for a while. The MK1775 methylcellulose solution can be stored at 4°C for a week.

Wee1 Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID