Adavosertib (MK-1775)

製品コードS1525

Adavosertib (MK-1775)化学構造

分子量(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.

サイズ 価格(税別)  
JPY 39508.00
JPY 28220.00
JPY 44820.00
JPY 78020.00
JPY 127820.00

カスタマーフィードバック(7)

  • Panobinostat enhances the antitumor activity of MK-1775 in a BxPC-3 xenograft model. Tumor specimens were fixed in 10% formalin, embedded in paraffin, and cut into 4 μM-thick slides for H&E staining.

    Cancer Letters, 2015, 356(200): 656–668 . Adavosertib (MK-1775) purchased from Selleck.

    Diagnostic AML blasts from patients either at first diagnosis or at relapse are equally sensitive to MK-1775. Freshly isolated cells from patient AML#10 were purified by standard Ficoll-Hypaque density centrifugation. AML#10, HL-60, and HL-60/Ara-C cells were treated with MK-1775 for 48 h. Whole cell lysates were subjected to Western blotting and probed with anti-p-CDK1, -CDK1, -p-CDK2, -CDK2, -γH2AX, or -β-actin antibody.

    J Hematol Oncol 2014 7:53. Adavosertib (MK-1775) purchased from Selleck.

  • Front Oncol, 2018, 8:143. Adavosertib (MK-1775) purchased from Selleck.

    (C) Nude mice bearing MDA-MB-231 xenograft tumors were treated with vehicle, MK-1775, cisplatin, or a combination of cisplatin and MK-1775 for 28 days and tumor volumes were measured. Data are presented as the mean of 8 tumors for each group ± SEM.

    Sci Rep, 2017, 7:43517. Adavosertib (MK-1775) purchased from Selleck.

  • GH activates STAT5 and ERK in breast cancer cells. T47D cells were pretreated for 2 hours with vehicle (dimethylsulfoxide) or inhibitors for EGFR (AG1478, 15 uM) or JAK2 (AZD1480, 1 uM), followed by treatment with GH+E2 for 30 minutes.

    Endocrinology 2013 154(9), 3219-27. Adavosertib (MK-1775) purchased from Selleck.

    AZD1480 inhibits the JAK2/STAT3 pathway in vitro. HT29 cells were cultured in 24-well plates overnight and then treated with 1 uM AZD1480 for 2 h followed by 4 ng/ml, IL-6 for 2 h and the distribution of phosphorylated STAT3 was analyzed by immunofluorescence.

    Oncol Rep 2014 32(5), 1991-8. Adavosertib (MK-1775) purchased from Selleck.

  • Histopathological assessment of tumor response to MK-1775 alone and in combination with gemcitabine in a patient-derived osteosarcoma mouse model. A. H&E-stained paraffin sections were prepared to assess microscopic features of cell death and differentiation representative micrographs of B. Ki67 shows high immunoreactivity in the control, MK-1775, and combination treatments compared to gemcitabine treatment. C. Cleaved-caspase 3 images show high immunoreactivity in the MK-1775 and combination treatments compared to vehicle and gemcitabine treatment. D. Slides stained for γH2AX show high immunoreactivity in gemcitabine, MK-1775, and combination treatments compared to controls. E. Slides stained for Cyclin A show higher immunoreactivity in gemcitabine but not in control, MK-1775 alone or in combination treatments.

    PLoS One 2013 8(3), e57523. Adavosertib (MK-1775) purchased from Selleck.

製品安全説明書

Wee1阻害剤の選択性比較

生物活性

製品説明 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.
特性 The first reported Wee1 inhibitor.
ターゲット
Wee1 [1]
(Cell-free assay)
5.2 nM
体外試験

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]

細胞データ
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
ASPC-1 M{eydGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIezVIFKSzVyPUGzMlIhyrFiMT6xJO69VQ>? NEnETI0zPTR3OEm1OC=>
BxPC-3 NV[3UWYyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{jzVGlEPTB;MD64JOKyKDBwMEOg{txO MWGyOVQ2QDl3NB?=
CFPAC-1 M37vOmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUHJR|UxRTNwMzFCtUAxNjJizszN M164SlI2PDV6OUW0
HPAC NXn1fYd[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Ml3iTWM2OD1yLkWgxtEhOC5yMTFOwG0> MUWyOVQ2QDl3NB?=
MIAPaCa-2 MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2PSR2lEPTB;MD61JOKyKDBwMEWg{txO NF34U5QzPTR3OEm1OC=>
PANC-1 MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGDCW5dKSzVyPUGwMlYhyrFiMT6xJO69VQ>? NW\5VItZOjV2NUi5OVQ>
SK-N-BE (2) Mn7DS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVvJR|UxRTJwNPMAjeKy6oDLMD6zJO69VQ>? MYCyOVMxQDlzNh?=
SK-N-BE (2), PAN→MK NXzGXIRiT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFHnUm9KSzVyPUK2MlbjiIoEsfMAjVkvPiEQvF2= NILMZZUzPTNyOEmxOi=>
SK-N-BE (2), MK→PAN Mkm2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVTJR|UxRTJwNPMAjeKy6oDLMD6zJO69VQ>? MUKyOVMxQDlzNh?=
SK-N-AS MonMS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXPJR|UxRTBwNUFihKnDueLCiUCuNFIh|ryP MVeyOVMxQDlzNh?=
SK-N-DZ MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NY\2UXM{UUN3ME2wMlM36oDLwsJihKkxNjBzIN88US=> NUnVS45{OjV|MEi5NVY>
SK-N-AS NVfTNJl6SXCxcITvd4l{KEG|c3H5 NFTDVJg2ODBibl2= M2\ZW|Q5KGh? NXfpTodIcW6mdXPld{Bk\WyuIHHwc5B1d3Orcx?= NXT1bIlvOjV|MEi5NVY>
SK-N-DZ NH7pUWZCeG:ydH;zbZMhSXO|YYm= M1;yZVUxOCCwTR?= M1\3VFQ5KGh? MYfpcoR2[2W|IHPlcIwh[XCxcITvd4l{ NGXDPWgzPTNyOEmxOi=>
THP-1 MnGyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4mw[FEzPS9{NUCvOVAxKG6P NVnjeG5GPDhiaB?= NFPFUoxqdmO{ZXHz[ZMh[2WubDDk[YF1cCCrbjDhJINwdmOnboTyZZRqd25vZHXw[Y5l\W62IH3hco5meg>? NFjYRXgzPTB6NE[xOC=>
MV4-11 MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX22VFhWOTJ3L{K1NE82ODBibl2= MUe0PEBp NFn3bWdqdmO{ZXHz[ZMh[2WubDDk[YF1cCCrbjDhJINwdmOnboTyZZRqd25vZHXw[Y5l\W62IH3hco5meg>? NIrBSGEzPTB6NE[xOC=>
U937 MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NV\kXYVSOTJ3L{K1NE82ODBibl2= NH;0bHk1QCCq NHzyUo1qdmO{ZXHz[ZMh[2WubDDk[YF1cCCrbjDhJINwdmOnboTyZZRqd25vZHXw[Y5l\W62IH3hco5meg>? MUiyOVA5PDZzNB?=
HL-60 MmnMS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3nQNVEzPS9{NUCvOVAxKG6P MmGwOFghcA>? NXuwbIZKcW6lcnXhd4V{KGOnbHyg[IVifGhiaX6gZUBkd26lZX70doF1cW:wLXTldIVv\GWwdDDtZY5v\XJ? NXnvUo5bOjVyOES2NVQ>
OCI-AML3 NXHEe3FqT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIHPd4wyOjVxMkWwM|UxOCCwTR?= NGLPTWQ1QCCq NULO[GR7cW6lcnXhd4V{KGOnbHyg[IVifGhiaX6gZUBkd26lZX70doF1cW:wLXTldIVv\GWwdDDtZY5v\XJ? NUDlVFNiOjVyOES2NVQ>
MOLM-13 NXLW[mR1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlHtNVI2NzJ3MD:1NFAhdk1? NIPKUFc1QCCq NGLCcHlqdmO{ZXHz[ZMh[2WubDDk[YF1cCCrbjDhJINwdmOnboTyZZRqd25vZHXw[Y5l\W62IH3hco5meg>? M2fwVlI2ODh2NkG0
CMK NVjC[|RrS2WubDDWbYFjcWyrdImgRZN{[Xl? M1O0VVExNTFyMECwJI5O M33FVFczKGh? NHTXcIVz\WS3Y3XzJINmdGxidnnhcIljcXS7IHnuJIEh[2:wY3XueJJifGmxbj3k[ZBmdmSnboSgcYFvdmW{ M1r0SlI1QTZ{M{Ox
CMY NVTzSpFuS2WubDDWbYFjcWyrdImgRZN{[Xl? NHSyRoQyOC1zMECwNEBvVQ>? NV:2bm1SPzJiaB?= M3\sR5Jm\HWlZYOgZ4VtdCC4aXHsbYJqfHliaX6gZUBkd26lZX70doF1cW:wLXTldIVv\GWwdDDtZY5v\XJ? M{\lTVI1QTZ{M{Ox
Dayo NHrT[olIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHfB[mxKSzVyPUG1NEBvVQ>? NFHvRpozPDZ4MUmxNC=>
UW228 MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{XDXWlEPTB;MkOyJI5O NUPnSXlJOjR4NkG5NVA>
IST-MES1 MmrIR4VtdCCYaXHibYxqfHliQYPzZZk> M1fYRVE2OC9{NUCgcm0> NF\wbHA4OiCq MkT0[Y5p[W6lZYOgeIhmKGOrc4DsZZRqdiCleYTveI95cWNiZX\m[YN1KGmwIHGgZ49v[2WwdILheIlwdi2mZYDlcoRmdnRibXHucoVz NV7ESYJ7OjR|NkW3PFI>
IST-MES2 M{\n[WNmdGxiVnnhZoltcXS7IFHzd4F6 M3viTVE2OC9{NUCgcm0> NX62RWY6PzJiaB?= NVq1XZpF\W6qYX7j[ZMhfGinIHPpd5Bt[XSrbjDjfZRwfG:6aXOg[YZn\WO2IHnuJIEh[2:wY3XueJJifGmxbj3k[ZBmdmSnboSgcYFvdmW{ NV7WbmJ4OjR|NkW3PFI>
REN NGrNOpZE\WyuIG\pZYJqdGm2eTDBd5NigQ>? MljjNVUxNzJ3MDDuUS=> NFTQV4g4OiCq NGC1OWdmdmijbnPld{B1cGViY3nzdIxifGmwIHP5eI91d3irYzDl[oZm[3RiaX6gZUBkd26lZX70doF1cW:wLXTldIVv\GWwdDDtZY5v\XJ? MmC5NlQ{PjV5OEK=
NCI-H2452 NX;CWppTS2WubDDWbYFjcWyrdImgRZN{[Xl? NXywdVZvOTVyL{K1NEBvVQ>? NIGxUZQ4OiCq NHPqXo1mdmijbnPld{B1cGViY3nzdIxifGmwIHP5eI91d3irYzDl[oZm[3RiaX6gZUBkd26lZX70doF1cW:wLXTldIVv\GWwdDDtZY5v\XJ? MYmyOFM3PTd6Mh?=
MSTO-211H MYnD[YxtKF[rYXLpcIl1gSCDc4PhfS=> MVmxOVAwOjVyIH7N MUC3NkBp NU\ubZZ[\W6qYX7j[ZMhfGinIHPpd5Bt[XSrbjDjfZRwfG:6aXOg[YZn\WO2IHnuJIEh[2:wY3XueJJifGmxbj3k[ZBmdmSnboSgcYFvdmW{ MUSyOFM3PTd6Mh?=
NCI-H2052 MmrwR4VtdCCYaXHibYxqfHliQYPzZZk> MUOxOVAwOjVyIH7N NWDaWld2PzJiaB?= MnT6[Y5p[W6lZYOgeIhmKGOrc4DsZZRqdiCleYTveI95cWNiZX\m[YN1KGmwIHGgZ49v[2WwdILheIlwdi2mZYDlcoRmdnRibXHucoVz NUK2SI1[OjR|NkW3PFI>
WEE1 MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYHDVWtWUUN3ME21MlIhdk1? Mm\hNlM3QTl4NUW=
CDC2 MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkXGTWM2OO,:nkGwNFAhdk1? NXWxSI1TOjN4OUm2OVU>
CDK7 MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MX7JR|Ux97zgMUCwNEBvVQ>? MXGyN|Y6QTZ3NR?=
MYT1 M2DyXmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlLVTWM2OD13M{Cgcm0> M1rReFI{Pjl7NkW1
T98G  MmXORZBweHSxc3nzJGF{e2G7 NInyblAyODBxMkWwJI5O MmDWOkBp M{Ljc4VvcGGwY3XzJJJi\GmjdHnvck1qdmS3Y3XkJINmdGxia3nscIlv\w>? NVW3TVRGOjF7OUK3PVM>
A549 MXLBdI9xfG:|aYOgRZN{[Xl? NV3LfIx[OjByIH7N Mmm4NUBp NHv5ZoFz[WSrb4PlcpNqfGm8ZYOgUnNEVENiY3XscJMhcW5iYTDwOVMu\GWyZX7k[Y51KG2jbn7ldi=> NIHpUmYzOTd7OUCzNy=>
H460 NXfROWRFSXCxcITvd4l{KEG|c3H5 NV3PbYU4OjByIH7N NIXjdYQyKGh? M2PWOZJi\Gmxc3Xud4l1cXqnczDOV2NNSyClZXzsd{BqdiCjIIC1N{1l\XCnbnTlcpQhdWGwbnXy NWTaWpJvOjF5OUmwN|M>
H1299 MlPSRZBweHSxc3nzJGF{e2G7 M4XzXFIxOCCwTR?= MoXWNUBp MnrTdoFlcW:|ZX7zbZRqgmW|IF7TR2xEKGOnbHzzJIlvKGFicEWzMYRmeGWwZHXueEBu[W6wZYK= M4PY[FIyPzl7MEOz
Calu-6  MkLXRZBweHSxc3nzJGF{e2G7 MYSyNFAhdk1? NUj3[HdwOSCq MWfyZYRqd3OnboPpeIl7\XNiTmPDUGMh[2WubIOgbY4h[SCyNUOt[IVx\W6mZX70JI1idm6nch?= NVrsN2hqOjF5OUmwN|M>
WiDr MkjTT4lv[XOnIFHzd4F6ew>? NF;FVnoyOC1zMECwNEBvVQ>? MUm4JIg> MoribY5pcWKrdIOgdIhwe3Cqb4L5cIF1cW:wIH;mJGNFSzJiYYSgWJlzOTVid3n0bEBidiCHQ{WwxsB3[Wy3ZTDv[kA5PSCwbX;sM2wheHKndILlZZRm\CC5aYToJIdmdWOrdHHibY5m NXji[nloOTl6OEe1OFU>

他の多くの細胞株試験データをご覧になる場合はこちらをクリックして下さい

体内試験 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]

お薦めの試験操作(参考用のみ)

キナーゼ試験:

[1]

+ 展開

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.
細胞試験:

[1]

+ 展開
  • 細胞株: WiDr, NCI-H1299, TOV21G, and HeLa
  • 濃度: Dissolved in DMSO, final concentrations ~10 μM
  • 反応時間: 24 hours
  • 実験の流れ:

    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.


    (参考用のみ)
動物試験:

[1]

+ 展開
  • 動物モデル: Immunodeficient nude rats (F344/NJcl-rnu) bearing WiDr, HeLa-luc, or TOV21G-shp53 tumors
  • 製剤: Prepared in a vehicle of 0.5% methylcellulose solution
  • 投薬量: ~20 mg/kg/day
  • 投与方法: Orally
    (参考用のみ)

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 左から(NMPから)右の順に溶剤を製品に加えます(文献ではなく、Selleckの実験によるデータ):
2% DMSO+30% PEG 300+5% Tween 80+ddH2O
混合させたのち直ちに使用することを推奨します。
5mg/mL

* 溶解度測定はSelleck技術部門によって行われており、その他文献に示されている溶解度と差異がある可能性がありますが、同一ロットの生産工程で起きる正常な現象ですからご安心ください。

化学情報

分子量 500.6
化学式

C27H32N8O2

CAS No. 955365-80-7
保管
in solvent
別名 N/A

便利ツール

モル濃度計算器

モル濃度計算器

求めたい質量、体積または濃度を計算してください。

質量 (g) = 濃度 (mol/L) x 体積 (L) x 分子量 (g/mol)

モル濃度計算器方程式

  • 質量
    濃度
    体積
    分子量

*貯蔵液を準備するとき、常に、オンであるとわかる製品のバッチに特有の分子量を使って、を通してラベルとMSDS/COA(製品ページで利用可能な)。

希釈計算器

希釈計算器

貯蔵液を準備するために必要な希釈率を計算してください。Selleck希釈計算器は、以下の方程式に基づきます:

開始濃度 x 開始体積 = 最終濃度 x 最終体積

希釈の計算式

この方程式は、一般に略語を使われます:C1V1 = C2V2 ( 入力 出力 )

  • C1
    V1
    C2
    V2

常に貯蔵液を準備するとき、小びんラベルとMSDS/COA(オンラインで利用できる)で見つかる製品のバッチに特有の分子量を使ってください。

連続希釈計算器方程式

  • 連続希釈剤

  • 計算結果

  • 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):
分子量計算器

分子量计算器

そのモル質量と元素組成を計算するために、合成物の化学式を入力してください:

総分子量:g/mol

チップス: 化学式は大文字と小文字の区別ができます。C10H16N2O2 c10h16n2o2

モル濃度計算器

質量 濃度 体積 分子量

臨床試験

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02037230 Recruiting Adenocarcinoma of the Pancreas University of Michigan 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
NCT01357161 Completed Ovarian Cancer Merck Sharp & Dohme Corp. July 26 2011 Phase 2
NCT01164995 Unknown status Epithelial Ovarian Cancer The Netherlands Cancer Institute|Merck Sharp & Dohme Corp. July 2010 Phase 2
NCT01076400 Terminated Cervical Cancer Merck Sharp & Dohme Corp. May 31 2010 Phase 1|Phase 2
NCT01047007 Terminated Solid Tumors Merck Sharp & Dohme Corp. January 18 2010 Phase 1

技術サポート

ストックの作り方、阻害剤の保管方法、細胞実験や動物実験の際に注意すべき点など、製品を取扱う時に問い合わせが多かった質問に対しては取扱説明書でお答えしています。

Handling Instructions

他に質問がある場合は、お気軽にお問い合わせください。

  • * 必須

よくある質問(FAQ)

  • 質問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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細胞株 試験類型 濃度 培養時間 溶剤類型 活性叙述 PMID