Adavosertib (MK-1775)

目录号:S1525

Adavosertib (MK-1775) Chemical Structure

Molecular Weight(MW): 500.6

MK-1775是一种有效的,高选择性Wee1抑制剂,无细胞试验中IC50为5.2 nM;阻碍G2期DNA损伤检验点。Phase 2。

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RMB 1960.96 现货
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客户使用Selleck该产品发表文献21篇:

产品安全说明书

Wee1抑制剂选择性比较

生物活性

产品描述 MK-1775是一种有效的,高选择性Wee1抑制剂,无细胞试验中IC50为5.2 nM;阻碍G2期DNA损伤检验点。Phase 2。
特性 首个报道的 Wee1抑制剂。
靶点
Wee1 [1]
(Cell-free assay)
5.2 nM
体外研究

MK-1775以ATP竞争的方式抑制Wee1激酶。与作用于Wee1相比,MK-1775对Yes的效能低2-到3-倍,IC50为14 nM,对7种其他激酶的效能低10倍,1 μM浓度下抑制率>80%,比对人Myt 1选择性高100倍以上,并抑制周期蛋白依赖性激酶1 (CDC2) 在可选择位点(Thr14) 的磷酸化作用。通过阻断负荷突变型p53的WiDr细胞中Wee1活性,废止DNA损伤检控点,MK-1775治疗抑制Tyr15 (CDC2Y15)位点的CDC2基础磷酸化作用,EC50为49 nM,并剂量依赖性抑制gemcitabine-,carboplatin- 或cisplatin-诱导的CDC2磷酸化和细胞周期阻滞,EC50分别为82 nM和81 nM,180 nM 和163 nM,以及159 nM 和 160 nM。30-100 nM 的MK-1775单独治疗在WiDr 和 H1299细胞中没有显著的抗增殖作用,而300 nM的MK-1775足以抑制>80%的Wee1,表现出温和但显著的抗增殖作用,在WiDr和H1299细胞中抑制率分别为34.1%和28.4%。[1]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
ASPC-1 Ml;CS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWjJR|UxRTF|LkKgxtEhOS5zIN88US=> Mn\4NlU1PTh7NUS=
BxPC-3 M1rmemdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXvJR|UxRTBwODFCtUAxNjB|IN88US=> NGfkfYszPTR3OEm1OC=>
CFPAC-1 NEXLdZZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGPsR4pKSzVyPUOuN{DDuSByLkKg{txO NXHzO3BTOjV2NUi5OVQ>
HPAC MkDkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIrRPZZKSzVyPUCuOUDDuSByLkCxJO69VQ>? MXeyOVQ2QDl3NB?=
MIAPaCa-2 MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MX7JR|UxRTBwNTFCtUAxNjB3IN88US=> MV2yOVQ2QDl3NB?=
PANC-1 NWC3Z4tNT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MULJR|UxRTFyLk[gxtEhOS5zIN88US=> NUjKW3FKOjV2NUi5OVQ>
SK-N-BE (2) NXK5UmNET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYfJR|UxRTJwNPMAjeKy6oDLMD6zJO69VQ>? NXnoOZF2OjV|MEi5NVY>
SK-N-BE (2), PAN→MK M4DKdWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MY\JR|UxRTJ4LkdihKnDueLCiUmuOkDPxE1? NGfCdoIzPTNyOEmxOi=>
SK-N-BE (2), MK→PAN MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlTUTWM2OD1{LkVihKnDueLCiUCuN{DPxE1? M1HaOFI2OzB6OUG2
SK-N-AS NYDzdmY6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWrJR|UxRTBwNUFihKnDueLCiUCuNFIh|ryP MkDsNlU{ODh7MU[=
SK-N-DZ NXXidGk1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEDhXnhKSzVyPUCuN|bjiIoEsfMAjVAvODFizszN NX35NFI4OjV|MEi5NVY>
SK-N-AS MXLBdI9xfG:|aYOgRZN{[Xl? Ml:1OVAxKG6P M1vQflQ5KGh? NV3SUWI4cW6mdXPld{Bk\WyuIHHwc5B1d3Orcx?= M{jqRlI2OzB6OUG2
SK-N-DZ MlPWRZBweHSxc3nzJGF{e2G7 NEfZR4Y2ODBibl2= NILJWY01QCCq MVzpcoR2[2W|IHPlcIwh[XCxcITvd4l{ NVLmeHBTOjV|MEi5NVY>
THP-1 NW\Ub4NDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFnYXm0yOjVxMkWwM|UxOCCwTR?= M{fXUVQ5KGh? MkXHbY5kemWjc3XzJINmdGxiZHXheIghcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI> M{DjblI2ODh2NkG0
MV4-11 M4TEO2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIDFfFQyOjVxMkWwM|UxOCCwTR?= M33jZ|Q5KGh? MXLpcoNz\WG|ZYOgZ4VtdCCmZXH0bEBqdiCjIHPvcoNmdnS{YYTpc44u\GWyZX7k[Y51KG2jbn7ldi=> MWmyOVA5PDZzNB?=
U937 MmXES5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGDENmwyOjVxMkWwM|UxOCCwTR?= NYDMVok{PDhiaB?= M1L0folv[3KnYYPld{Bk\WyuIHTlZZRpKGmwIHGgZ49v[2WwdILheIlwdi2mZYDlcoRmdnRibXHucoVz NGm3XW8zPTB6NE[xOC=>
HL-60 NIW4c|dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXyxNlUwOjVyL{WwNEBvVQ>? M4joZlQ5KGh? Mk\5bY5kemWjc3XzJINmdGxiZHXheIghcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI> NWXXOHZnOjVyOES2NVQ>
OCI-AML3 NUTiU5dUT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnGwNVI2NzJ3MD:1NFAhdk1? M2XXflQ5KGh? NIG1UXdqdmO{ZXHz[ZMh[2WubDDk[YF1cCCrbjDhJINwdmOnboTyZZRqd25vZHXw[Y5l\W62IH3hco5meg>? NVjnelFUOjVyOES2NVQ>
MOLM-13 M3[2Z2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHXkZWIyOjVxMkWwM|UxOCCwTR?= NGD6SFY1QCCq M1:2VIlv[3KnYYPld{Bk\WyuIHTlZZRpKGmwIHGgZ49v[2WwdILheIlwdi2mZYDlcoRmdnRibXHucoVz NVTDW5BOOjVyOES2NVQ>
CMK MVjD[YxtKF[rYXLpcIl1gSCDc4PhfS=> M4LtNVExNTFyMECwJI5O MW[3NkBp MlXKdoVlfWOnczDj[YxtKH[rYXzpZol1gSCrbjDhJINwdmOnboTyZZRqd25vZHXw[Y5l\W62IH3hco5meg>? M2nkblI1QTZ{M{Ox
CMY MXfD[YxtKF[rYXLpcIl1gSCDc4PhfS=> M4nzSVExNTFyMECwJI5O MYi3NkBp MXjy[YR2[2W|IHPlcIwhfmmjbHnibZR6KGmwIHGgZ49v[2WwdILheIlwdi2mZYDlcoRmdnRibXHucoVz M3;jelI1QTZ{M{Ox
Dayo MoXXS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3K0XGlEPTB;MUWwJI5O M13CSFI1PjZzOUGw
UW228 MmPYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mmq2TWM2OD1{M{Kgcm0> M3LyWVI1PjZzOUGw
IST-MES1 NWfEb3pZS2WubDDWbYFjcWyrdImgRZN{[Xl? M{T2W|E2OC9{NUCgcm0> NUXacmtGPzJiaB?= M2rVXoVvcGGwY3XzJJRp\SClaYPwcIF1cW5iY4n0c5RwgGmlIHXm[oVkfCCrbjDhJINwdmOnboTyZZRqd25vZHXw[Y5l\W62IH3hco5meg>? NWH5RWtpOjR|NkW3PFI>
IST-MES2 NXn3d4RJS2WubDDWbYFjcWyrdImgRZN{[Xl? NVfvbVdLOTVyL{K1NEBvVQ>? M4HEd|czKGh? MVvlcohidmOnczD0bIUh[2m|cHzheIlvKGO7dH;0c5hq[yCnZn\lZ5QhcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI> M2rNUFI1OzZ3N{iy
REN MlPTR4VtdCCYaXHibYxqfHliQYPzZZk> MX2xOVAwOjVyIH7N NUfOTm44PzJiaB?= NULlPGVF\W6qYX7j[ZMhfGinIHPpd5Bt[XSrbjDjfZRwfG:6aXOg[YZn\WO2IHnuJIEh[2:wY3XueJJifGmxbj3k[ZBmdmSnboSgcYFvdmW{ NIjheZczPDN4NUe4Ni=>
NCI-H2452 MlPsR4VtdCCYaXHibYxqfHliQYPzZZk> NV3uN3JnOTVyL{K1NEBvVQ>? NIe1RXI4OiCq NIDX[WRmdmijbnPld{B1cGViY3nzdIxifGmwIHP5eI91d3irYzDl[oZm[3RiaX6gZUBkd26lZX70doF1cW:wLXTldIVv\GWwdDDtZY5v\XJ? NF3TZoEzPDN4NUe4Ni=>
MSTO-211H M4HtU2NmdGxiVnnhZoltcXS7IFHzd4F6 Mn\uNVUxNzJ3MDDuUS=> NGLZblg4OiCq M3u0fIVvcGGwY3XzJJRp\SClaYPwcIF1cW5iY4n0c5RwgGmlIHXm[oVkfCCrbjDhJINwdmOnboTyZZRqd25vZHXw[Y5l\W62IH3hco5meg>? MVSyOFM3PTd6Mh?=
NCI-H2052 M{\KdmNmdGxiVnnhZoltcXS7IFHzd4F6 MmPNNVUxNzJ3MDDuUS=> M{XxflczKGh? NELXWXZmdmijbnPld{B1cGViY3nzdIxifGmwIHP5eI91d3irYzDl[oZm[3RiaX6gZUBkd26lZX70doF1cW:wLXTldIVv\GWwdDDtZY5v\XJ? MXqyOFM3PTd6Mh?=
WEE1 MXTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYTF[XBLUUN3ME21MlIhdk1? MmS4NlM3QTl4NUW=
CDC2 M2[1dmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFLJRotKSzVy78{eNVAxOCCwTR?= MUSyN|Y6QTZ3NR?=
CDK7 NWTU[YhDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3nvVWlEPTExvK6xNFAxKG6P NVq5VnQ2OjN4OUm2OVU>
MYT1 NWTkeJpET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH;Lb4tKSzVyPUWzNEBvVQ>? MYqyN|Y6QTZ3NR?=
T98G  NFLYZ21CeG:ydH;zbZMhSXO|YYm= M4\xVlExOC9{NUCgcm0> Mn75OkBp M2Hxc4VvcGGwY3XzJJJi\GmjdHnvck1qdmS3Y3XkJINmdGxia3nscIlv\w>? NWj6VYRHOjF7OUK3PVM>
A549 Mn34RZBweHSxc3nzJGF{e2G7 M4\wWVIxOCCwTR?= M3rxPVEhcA>? NE[xVpdz[WSrb4PlcpNqfGm8ZYOgUnNEVENiY3XscJMhcW5iYTDwOVMu\GWyZX7k[Y51KG2jbn7ldi=> NU\YSWVMOjF5OUmwN|M>
H460 NIXB[25CeG:ydH;zbZMhSXO|YYm= MXSyNFAhdk1? Mm\5NUBp NIfxOJhz[WSrb4PlcpNqfGm8ZYOgUnNEVENiY3XscJMhcW5iYTDwOVMu\GWyZX7k[Y51KG2jbn7ldi=> NXrnVlZ7OjF5OUmwN|M>
H1299 NULXbo1wSXCxcITvd4l{KEG|c3H5 MUOyNFAhdk1? NXvjVXR[OSCq NUTSVFQ5emGmaX;z[Y5{cXSrenXzJG5US0yFIHPlcIx{KGmwIHGgdFU{NWSncHXu[IVvfCCvYX7u[ZI> NEn3SnkzOTd7OUCzNy=>
Calu-6  NYmyOFRlSXCxcITvd4l{KEG|c3H5 MX6yNFAhdk1? NWPnW4FUOSCq MXXyZYRqd3OnboPpeIl7\XNiTmPDUGMh[2WubIOgbY4h[SCyNUOt[IVx\W6mZX70JI1idm6nch?= NHT6ZZIzOTd7OUCzNy=>
WiDr M3nzUGtqdmG|ZTDBd5NigXN? MnWwNVAuOTByMECgcm0> MXO4JIg> Mo\YbY5pcWKrdIOgdIhwe3Cqb4L5cIF1cW:wIH;mJGNFSzJiYYSgWJlzOTVid3n0bEBidiCHQ{WwxsB3[Wy3ZTDv[kA5PSCwbX;sM2wheHKndILlZZRm\CC5aYToJIdmdWOrdHHibY5m M1vNXlE6QDh5NUS1

... 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
体内研究 MK-1775(~20 mg/kg)单独治疗对WiDr异种移植物表现出最小的抗肿瘤作用,在大鼠体内第3天时T/C为69%。在裸鼠HeLa-luc和TOV21G-shp53异种移植模型中,MK-1775单独的抗肿瘤效能是温和的。[1]

推荐的实验操作(此推荐来自于公开的文献所以Selleck并不保证其有效性)

激酶实验:

[1]

+ 展开

体外激酶试验:

使用重组人Wee1。激酶反应使用10 μM ATP,1.0 μCi of [γ-33P]ATP,和2.5 μg poly(Lys, Tyr)作为底物,在逐渐增加浓度的MK-1775存在下,在30°C环境中进行30分钟。整合到底物的放射性被捕获到MultiScreen-PH平板,在液体闪烁计数器上计数。
细胞实验:

[1]

+ 展开
  • Cell lines: WiDr,NCI-H1299,TOV21G,和 HeLa细胞
  • Concentrations: 在DMSO中溶解,终浓度为~10 μM
  • Incubation Time: 24小时
  • Method: 细胞在gemcitabine存在或不存在下处理24小时,然后用MK-1775再处理24小时。细胞活性使用SpectraMax通过WST-8试剂盒测定。细胞内caspase-3/7活性使用Caspase-3/7 Glo试剂盒测定。
    (Only for Reference)
动物实验:

[1]

+ 展开
  • Animal Models: 负荷WiDr,HeLa-luc,或TOV21G-shp53肿瘤的免疫缺陷裸鼠(F344/NJcl-rnu)
  • Formulation: 在0.5%甲基纤维素溶液载体中制备
  • Dosages: ~20 mg/kg/day
  • Administration: 口服
    (Only for Reference)

溶解度 (25°C)

体外 DMSO 80 mg/mL (159.8 mM)
Ethanol 10 mg/mL (19.97 mM)
Water 0.0001 mg/mL (0.0 mM)
体内 从左到右依次将纯溶剂加入产品,现配现用(数据来自Selleck实验检测而非文献):
2% DMSO+30% PEG 300+5% Tween 80+ddH2O
5mg/mL

* 溶解度检测是由Selleck技术部门检测的,可能会和文献中提供的溶解度有所差异,这是由于生产工艺和批次不同产生的正常现象。请按照顺序依次加入各个纯溶剂。

化学数据

分子量 500.6
化学式

C27H32N8O2

CAS号 955365-80-7
稳定性 powder
in solvent
别名 N/A

计算器

摩尔浓度计算器

摩尔浓度计算器

本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系,公式为:

质量 (g) = 浓度 (mol/L) x 体积 (L) x 分子量 (g/mol)

摩尔浓度计算公式

  • 质量
    浓度
    体积
    分子量

*在配置溶液时,请务必参考Selleck产品标签上、MSDS / COA(可在Selleck的产品页面获得)批次特异的分子量使用本工具。

稀释计算器

稀释计算器

用本工具协助配置特定浓度的溶液,使用的计算公式为:

开始浓度 x 开始体积 = 最终浓度 x 最终体积

稀释公式

稀释公式一般简略地表示为: C1V1 = C2V2 ( 输入 输出 )

  • C1
    V1
    C2
    V2

在配置溶液时,请务必参考Selleck产品标签上、MSDS / COA(可在Selleck的产品页面获得)批次特异的分子量使用本工具。.

连续稀释计算器方程

  • 连续稀释

  • 计算结果

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):
分子量计算器

分子量计算器

通过输入化合物的化学式来计算其分子量:

总分子量:g/mol

注:化学分子式大小写敏感。C10H16N2O2 c10h16n2o2

摩尔浓度计算器

质量 浓度 体积 分子量
计算

临床试验信息

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02037230 Active not recruiting Adenocarcinoma of the Pancreas University of Michigan Rogel Cancer Center January 2014 Phase 1|Phase 2
NCT02037230 Active not recruiting Adenocarcinoma of the Pancreas University of Michigan Rogel Cancer Center January 2014 Phase 1|Phase 2
NCT01748825 Active not recruiting Neoplasms|Lymphoma National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC) December 19 2012 Phase 1
NCT01748825 Active not recruiting Neoplasms|Lymphoma National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC) December 19 2012 Phase 1
NCT01357161 Completed Ovarian Cancer Merck Sharp & Dohme Corp. July 26 2011 Phase 2
NCT01357161 Completed Ovarian Cancer Merck Sharp & Dohme Corp. July 26 2011 Phase 2

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操作手册

如果有其他问题,请给我们留言。

  • * 必填项

常见问题及建议解决方法

  • 问题 1:

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

  • 回答:

    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.

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID