MK-1775 化学構造
分子量: 500.6

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製品説明

  • Compare Wee1 Inhibitors
    Wee1製品生物活性の比較
  • 研究分野
  • Combination Therapy
    併用療法

製品の説明

生物活性

製品説明 MK-1775は、有力で選択的なWee1</b> 阻害剤で、IC50 が 5.2 nMです。
ターゲット

Wee1

IC50

5.2 nM [1]

In vitro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]
Cell Data
Cell LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
ASPC-1 NHLCPIlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3nW[mlEPTB;MUOuNkDDuSBzLkGg{txO Mon4NlU1PTh7NUS=
BxPC-3 NXLiWIFLT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWXj[2h7UUN3ME2wMlghyrFiMD6wN{DPxE1? NXTLVXVTOjV2NUi5OVQ>
CFPAC-1 MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mm\XTWM2OD1|LkOgxtEhOC5{IN88US=> MkXKNlU1PTh7NUS=
HPAC M{Pkd2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXLJR|UxRTBwNTFCtUAxNjBzIN88US=> M3f0blI2PDV6OUW0
MIAPaCa-2 NV3pdFI3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWW2[2g5UUN3ME2wMlUhyrFiMD6wOUDPxE1? MlzmNlU1PTh7NUS=
PANC-1 MmnVS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MojjTWM2OD1zMD62JOKyKDFwMTFOwG0> NGDOd2szPTR3OEm1OC=>
SK-N-BE (2) NVThTZN[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1vDXGlEPTB;Mj605qCKyrIkgJmwMlMh|ryP M{XCZlI2OzB6OUG2
SK-N-BE (2), PAN→MK NWW2SJVnT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXz2dZpLUUN3ME2yOk436oDLwsJihKk6NjZizszN MlzoNlU{ODh7MU[=
SK-N-BE (2), MK→PAN MnjRS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFi3eoRKSzVyPUKuOQKBkcLz4pEJNE4{KM7:TR?= NV\2dGdLOjV|MEi5NVY>
SK-N-AS MljmS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUXJR|UxRTBwNUFihKnDueLCiUCuNFIh|ryP NVnyUJQ4OjV|MEi5NVY>
SK-N-DZ MUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYnKPXFzUUN3ME2wMlM36oDLwsJihKkxNjBzIN88US=> M3nPNFI2OzB6OUG2
SK-N-AS MXjBdI9xfG:|aYOgRZN{[Xl? M2CyUVUxOCCwTR?= NF7RNWE1QCCq Mn:xbY5lfWOnczDj[YxtKGGyb4D0c5Nqew>? NFG2dXIzPTNyOEmxOi=>
SK-N-DZ NV\Ve5drSXCxcITvd4l{KEG|c3H5 M{O3O|UxOCCwTR?= MVm0PEBp NXXzNHRCcW6mdXPld{Bk\WyuIHHwc5B1d3Orcx?= M130[lI2OzB6OUG2
THP-1 MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MonnNVI2NzJ3MD:1NFAhdk1? Mn7BOFghcA>? NXvpPIdpcW6lcnXhd4V{KGOnbHyg[IVifGhiaX6gZUBkd26lZX70doF1cW:wLXTldIVv\GWwdDDtZY5v\XJ? NYT0VpBMOjVyOES2NVQ>
MV4-11 MXTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2rhd|EzPS9{NUCvOVAxKG6P M{DSR|Q5KGh? M{PFWIlv[3KnYYPld{Bk\WyuIHTlZZRpKGmwIHGgZ49v[2WwdILheIlwdi2mZYDlcoRmdnRibXHucoVz M{n6cFI2ODh2NkG0
U937 Ml;KS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NF3xRZoyOjVxMkWwM|UxOCCwTR?= MYq0PEBp M1HSW4lv[3KnYYPld{Bk\WyuIHTlZZRpKGmwIHGgZ49v[2WwdILheIlwdi2mZYDlcoRmdnRibXHucoVz NGeyepYzPTB6NE[xOC=>
HL-60 NFnjW5NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4TQe|EzPS9{NUCvOVAxKG6P Mln4OFghcA>? NH3oOHJqdmO{ZXHz[ZMh[2WubDDk[YF1cCCrbjDhJINwdmOnboTyZZRqd25vZHXw[Y5l\W62IH3hco5meg>? NXmyVlRJOjVyOES2NVQ>
OCI-AML3 NUi2UodET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4jwSVEzPS9{NUCvOVAxKG6P NEntXXg1QCCq Ml20bY5kemWjc3XzJINmdGxiZHXheIghcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI> NH20[nUzPTB6NE[xOC=>
MOLM-13 NEjHRnZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGWwdWUyOjVxMkWwM|UxOCCwTR?= NIexb4g1QCCq MljhbY5kemWjc3XzJINmdGxiZHXheIghcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI> MWiyOVA5PDZzNB?=
CMK M4GxUGNmdGxiVnnhZoltcXS7IFHzd4F6 M3[5XFExNTFyMECwJI5O MUC3NkBp MX\y[YR2[2W|IHPlcIwhfmmjbHnibZR6KGmwIHGgZ49v[2WwdILheIlwdi2mZYDlcoRmdnRibXHucoVz MnXhNlQ6PjJ|M{G=
CMY M3PSfmNmdGxiVnnhZoltcXS7IFHzd4F6 MmLiNVAuOTByMECgcm0> MlLGO|IhcA>? MWfy[YR2[2W|IHPlcIwhfmmjbHnibZR6KGmwIHGgZ49v[2WwdILheIlwdi2mZYDlcoRmdnRibXHucoVz NH;NeG0zPDl4MkOzNS=>
Dayo MlLxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHvuNFNKSzVyPUG1NEBvVQ>? NFTXU|YzPDZ4MUmxNC=>
UW228 MkD4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MofiTWM2OD1{M{Kgcm0> MXiyOFY3OTlzMB?=
IST-MES1 M1PCNWNmdGxiVnnhZoltcXS7IFHzd4F6 NXLvSZQyOTVyL{K1NEBvVQ>? M4HIRlczKGh? MWjlcohidmOnczD0bIUh[2m|cHzheIlvKGO7dH;0c5hq[yCnZn\lZ5QhcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI> NUL3fXZoOjR|NkW3PFI>
IST-MES2 M2LFbmNmdGxiVnnhZoltcXS7IFHzd4F6 M2ftTFE2OC9{NUCgcm0> NVHSXGR4PzJiaB?= NFz3XIlmdmijbnPld{B1cGViY3nzdIxifGmwIHP5eI91d3irYzDl[oZm[3RiaX6gZUBkd26lZX70doF1cW:wLXTldIVv\GWwdDDtZY5v\XJ? MWmyOFM3PTd6Mh?=
REN M{LVUWNmdGxiVnnhZoltcXS7IFHzd4F6 NILETJAyPTBxMkWwJI5O NXXVV2lLPzJiaB?= M16zV4VvcGGwY3XzJJRp\SClaYPwcIF1cW5iY4n0c5RwgGmlIHXm[oVkfCCrbjDhJINwdmOnboTyZZRqd25vZHXw[Y5l\W62IH3hco5meg>? MUiyOFM3PTd6Mh?=
NCI-H2452 MWfD[YxtKF[rYXLpcIl1gSCDc4PhfS=> MX[xOVAwOjVyIH7N MYC3NkBp MWTlcohidmOnczD0bIUh[2m|cHzheIlvKGO7dH;0c5hq[yCnZn\lZ5QhcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI> Mmm2NlQ{PjV5OEK=
MSTO-211H NIO0UVRE\WyuIG\pZYJqdGm2eTDBd5NigQ>? MlXTNVUxNzJ3MDDuUS=> NFnye|Y4OiCq M1\4[oVvcGGwY3XzJJRp\SClaYPwcIF1cW5iY4n0c5RwgGmlIHXm[oVkfCCrbjDhJINwdmOnboTyZZRqd25vZHXw[Y5l\W62IH3hco5meg>? MljpNlQ{PjV5OEK=
NCI-H2052 MkHyR4VtdCCYaXHibYxqfHliQYPzZZk> NGjkelMyPTBxMkWwJI5O MUG3NkBp M1rkT4VvcGGwY3XzJJRp\SClaYPwcIF1cW5iY4n0c5RwgGmlIHXm[oVkfCCrbjDhJINwdmOnboTyZZRqd25vZHXw[Y5l\W62IH3hco5meg>? Ml\ONlQ{PjV5OEK=
WEE1 NEjZc|lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFu3bJFKSzVyPUWuNkBvVQ>? MWGyN|Y6QTZ3NR?=
CDC2 MmnTS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFr0PWlKSzVy78{eNVAxOCCwTR?= Ml7YNlM3QTl4NUW=
CDK7 MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVHJR|Ux97zgMUCwNEBvVQ>? NETkUoEzOzZ7OU[1OS=>
MYT1 NITHWJNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUHiUnlpUUN3ME21N|Ahdk1? M{jSZVI{Pjl7NkW1
T98G  MWjBdI9xfG:|aYOgRZN{[Xl? Mn\sNVAxNzJ3MDDuUS=> NHHNOpk3KGh? NYHlfVdU\W6qYX7j[ZMhemGmaXH0bY9vNWmwZIXj[YQh[2WubDDrbYxtcW6p MnPYNlE6QTJ5OUO=
A549 MXnBdI9xfG:|aYOgRZN{[Xl? NFHpZoQzODBibl2= NV\LcIFPOSCq MmLzdoFlcW:|ZX7zbZRqgmW|IF7TR2xEKGOnbHzzJIlvKGFicEWzMYRmeGWwZHXueEBu[W6wZYK= M{XIcFIyPzl7MEOz
H460 NHjJWGxCeG:ydH;zbZMhSXO|YYm= NWXCWW5uOjByIH7N MoHpNUBp M3LsWZJi\Gmxc3Xud4l1cXqnczDOV2NNSyClZXzsd{BqdiCjIIC1N{1l\XCnbnTlcpQhdWGwbnXy MoPaNlE4QTlyM{O=
H1299 MmjvRZBweHSxc3nzJGF{e2G7 NWn3fXJvOjByIH7N MWOxJIg> NVS1dpdXemGmaX;z[Y5{cXSrenXzJG5US0yFIHPlcIx{KGmwIHGgdFU{NWSncHXu[IVvfCCvYX7u[ZI> NIjXNIQzOTd7OUCzNy=>
Calu-6  MoC5RZBweHSxc3nzJGF{e2G7 NUPMbY5YOjByIH7N MYGxJIg> MoTvdoFlcW:|ZX7zbZRqgmW|IF7TR2xEKGOnbHzzJIlvKGFicEWzMYRmeGWwZHXueEBu[W6wZYK= M4LCZ|IyPzl7MEOz
WiDr NEPRXnJMcW6jc3WgRZN{[Xm| NHe3[2QyOC1zMECwNEBvVQ>? NGDqe4s5KGh? MXLpcohq[mm2czDwbI9{eGixconsZZRqd25ib3[gR2REOiCjdDDUfZIyPSC5aYToJIFvKEWFNUFCpJZidHWnIH;mJFg2KG6vb3yvUEBxemW2cnXheIVlKHerdHig[4Vu[2m2YXLpcoU> NIKwfHkyQTh6N{W0OS=>

... Click to View More Cell Line Experimental Data

In vivo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]
臨床試験 A Phase I dose escalation study evaluating MK-1775 in both monotherapy and in combination with Gemcitabine, Cisplatin, or Carboplatin in adult subjects with advanced solid tumors is currently ongoing.
特集 The first reported Wee1 inhibitor.

プロトコル (参考用のみ)

キナーゼアッセイ:

[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.

細胞アッセイ:

[1]

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.

動物実験:

[1]

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

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDogMonkeyBaboon
Weight (kg)0.020.151.80.40.0810312
Body Surface Area (m2)0.0070.0250.150.050.020.50.240.6
Km factor361285201220
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

参考

化学情報

Download MK-1775 SDF
分子量 500.6
化学式

C27H32N8O2

CAS No. 955365-80-7
保管 3年-20℃
2年-80℃in solvent
別名 N/A
溶解度 (25°C) * In vitro DMSO 80 mg/mL (159.8 mM)
Ethanol <1 mg/mL
Water 0.0001 mg/mL (0.0 mM)
In vivo 2% DMSO+30% PEG 300+5% Tween+ddH2O 5mg/mL
* <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.
化学名 2-allyl-1-(6-(2-hydroxypropan-2-yl)pyridin-2-yl)-6-(4-(4-methylpiperazin-1-yl)phenylamino)-1,2-dihydropyrazolo[3,4-d]pyrimidin-3-one

文献中の引用 (9)

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.

技術サポート&よくある質問(FAQ)

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* 必須

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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