MK-1775 化学構造
分子量: 500.6

高品質保証

カスタマーフィードバック(5)

Quality Control & MSDS

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 NVnTb3dqT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2PIXGlEPTB;MUOuNkDDuSBzLkGg{txO M{fWRlI2PDV6OUW0
BxPC-3 MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWjST3BpUUN3ME2wMlghyrFiMD6wN{DPxE1? M{PJXFI2PDV6OUW0
CFPAC-1 NYPXblJjT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M33NSGlEPTB;Mz6zJOKyKDBwMjFOwG0> MnrzNlU1PTh7NUS=
HPAC MmPrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NU\uN3ZCUUN3ME2wMlUhyrFiMD6wNUDPxE1? NY\ZcIJ5OjV2NUi5OVQ>
MIAPaCa-2 MlHLS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnPUTWM2OD1yLkWgxtEhOC5yNTFOwG0> MkjXNlU1PTh7NUS=
PANC-1 MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVK4VVQ1UUN3ME2xNE43KMLzIEGuNUDPxE1? NVu0XXVxOjV2NUi5OVQ>
SK-N-BE (2) MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2roNmlEPTB;Mj605qCKyrIkgJmwMlMh|ryP NHroOXEzPTNyOEmxOi=>
SK-N-BE (2), PAN→MK MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVXPS|dQUUN3ME2yOk436oDLwsJihKk6NjZizszN NUTH[GpCOjV|MEi5NVY>
SK-N-BE (2), MK→PAN Mn7zS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHHqVHdKSzVyPUKuOQKBkcLz4pEJNE4{KM7:TR?= NYjtW444OjV|MEi5NVY>
SK-N-AS MYDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGfYWZZKSzVyPUCuOVDjiIoEsfMAjVAvODJizszN M2HmeVI2OzB6OUG2
SK-N-DZ NGPPO5JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4XQUGlEPTB;MD6zOwKBkcLz4pEJNE4xOSEQvF2= M2\PUVI2OzB6OUG2
SK-N-AS NYDZ[WVuSXCxcITvd4l{KEG|c3H5 NF;MWYE2ODBibl2= NIC5fIQ1QCCq MUXpcoR2[2W|IHPlcIwh[XCxcITvd4l{ MUWyOVMxQDlzNh?=
SK-N-DZ MU\BdI9xfG:|aYOgRZN{[Xl? NVvNcmJEPTByIH7N NF60RZg1QCCq MYrpcoR2[2W|IHPlcIwh[XCxcITvd4l{ NFmzcJQzPTNyOEmxOi=>
THP-1 M3fiZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NH\BR20yOjVxMkWwM|UxOCCwTR?= NYO3bnR4PDhiaB?= NVTEfodocW6lcnXhd4V{KGOnbHyg[IVifGhiaX6gZUBkd26lZX70doF1cW:wLXTldIVv\GWwdDDtZY5v\XJ? NFfHSnMzPTB6NE[xOC=>
MV4-11 MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkjsNVI2NzJ3MD:1NFAhdk1? M33hOFQ5KGh? M1zUOIlv[3KnYYPld{Bk\WyuIHTlZZRpKGmwIHGgZ49v[2WwdILheIlwdi2mZYDlcoRmdnRibXHucoVz MWeyOVA5PDZzNB?=
U937 NVy2T4IyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1r6WFEzPS9{NUCvOVAxKG6P MYm0PEBp NVHFN5d[cW6lcnXhd4V{KGOnbHyg[IVifGhiaX6gZUBkd26lZX70doF1cW:wLXTldIVv\GWwdDDtZY5v\XJ? M1HiW|I2ODh2NkG0
HL-60 MXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{DISVEzPS9{NUCvOVAxKG6P MUS0PEBp NUOyRmVwcW6lcnXhd4V{KGOnbHyg[IVifGhiaX6gZUBkd26lZX70doF1cW:wLXTldIVv\GWwdDDtZY5v\XJ? MluwNlUxQDR4MUS=
OCI-AML3 MnnaS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mnm0NVI2NzJ3MD:1NFAhdk1? MonVOFghcA>? MkThbY5kemWjc3XzJINmdGxiZHXheIghcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI> MVyyOVA5PDZzNB?=
MOLM-13 MlfLS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFnsNJcyOjVxMkWwM|UxOCCwTR?= M1i5SVQ5KGh? MXjpcoNz\WG|ZYOgZ4VtdCCmZXH0bEBqdiCjIHPvcoNmdnS{YYTpc44u\GWyZX7k[Y51KG2jbn7ldi=> MnnuNlUxQDR4MUS=
CMK M{PnUmNmdGxiVnnhZoltcXS7IFHzd4F6 MnvJNVAuOTByMECgcm0> M4jRc|czKGh? NH\LTFVz\WS3Y3XzJINmdGxidnnhcIljcXS7IHnuJIEh[2:wY3XueJJifGmxbj3k[ZBmdmSnboSgcYFvdmW{ NV;Sb2lHOjR7NkKzN|E>
CMY NYPQbJVMS2WubDDWbYFjcWyrdImgRZN{[Xl? M2nQXlExNTFyMECwJI5O NULKfZFXPzJiaB?= NYPXTI0{emWmdXPld{Bk\WyuII\pZYxq[mm2eTDpckBiKGOxbnPlcpRz[XSrb36t[IVx\W6mZX70JI1idm6nch?= MoW4NlQ6PjJ|M{G=
Dayo MmewS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NG\sPWtKSzVyPUG1NEBvVQ>? MWWyOFY3OTlzMB?=
UW228 MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlGxTWM2OD1{M{Kgcm0> NXq1TIdwOjR4NkG5NVA>
IST-MES1 MUXD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NYfpWVF3OTVyL{K1NEBvVQ>? MUi3NkBp Ml\2[Y5p[W6lZYOgeIhmKGOrc4DsZZRqdiCleYTveI95cWNiZX\m[YN1KGmwIHGgZ49v[2WwdILheIlwdi2mZYDlcoRmdnRibXHucoVz MYGyOFM3PTd6Mh?=
IST-MES2 Ml65R4VtdCCYaXHibYxqfHliQYPzZZk> NELq[GsyPTBxMkWwJI5O M3vTR|czKGh? MUPlcohidmOnczD0bIUh[2m|cHzheIlvKGO7dH;0c5hq[yCnZn\lZ5QhcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI> MojCNlQ{PjV5OEK=
REN NYToW4ExS2WubDDWbYFjcWyrdImgRZN{[Xl? M3XoRlE2OC9{NUCgcm0> M4WySVczKGh? M3fFToVvcGGwY3XzJJRp\SClaYPwcIF1cW5iY4n0c5RwgGmlIHXm[oVkfCCrbjDhJINwdmOnboTyZZRqd25vZHXw[Y5l\W62IH3hco5meg>? M4TDZVI1OzZ3N{iy
NCI-H2452 MUDD[YxtKF[rYXLpcIl1gSCDc4PhfS=> M3Pte|E2OC9{NUCgcm0> MmHUO|IhcA>? NGfGTYhmdmijbnPld{B1cGViY3nzdIxifGmwIHP5eI91d3irYzDl[oZm[3RiaX6gZUBkd26lZX70doF1cW:wLXTldIVv\GWwdDDtZY5v\XJ? MVuyOFM3PTd6Mh?=
MSTO-211H NVPMXplMS2WubDDWbYFjcWyrdImgRZN{[Xl? M3fR[VE2OC9{NUCgcm0> NWPuXWVRPzJiaB?= MkK3[Y5p[W6lZYOgeIhmKGOrc4DsZZRqdiCleYTveI95cWNiZX\m[YN1KGmwIHGgZ49v[2WwdILheIlwdi2mZYDlcoRmdnRibXHucoVz NGLSemUzPDN4NUe4Ni=>
NCI-H2052 MoDCR4VtdCCYaXHibYxqfHliQYPzZZk> MVmxOVAwOjVyIH7N MkfZO|IhcA>? Mn3P[Y5p[W6lZYOgeIhmKGOrc4DsZZRqdiCleYTveI95cWNiZX\m[YN1KGmwIHGgZ49v[2WwdILheIlwdi2mZYDlcoRmdnRibXHucoVz NVj2b4hLOjR|NkW3PFI>
WEE1 NH\mOG1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXrJR|UxRTVwMjDuUS=> MknwNlM3QTl4NUW=
CDC2 MmPCS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mly2TWM2OO,:nkGwNFAhdk1? Ml;ONlM3QTl4NUW=
CDK7 NU\5SHM5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH2zO5RKSzVy78{eNVAxOCCwTR?= M4WzflI{Pjl7NkW1
MYT1 NHnDbI5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{TwSmlEPTB;NUOwJI5O M{C3T|I{Pjl7NkW1
T98G  NEDkZVJCeG:ydH;zbZMhSXO|YYm= MV:xNFAwOjVyIH7N MU[2JIg> MmLw[Y5p[W6lZYOgdoFlcWG2aX;uMYlv\HWlZXSgZ4VtdCCtaXzsbY5o M4TZOFIyQTl{N{mz
A549 NWC0ZoNZSXCxcITvd4l{KEG|c3H5 Mn\JNlAxKG6P MX:xJIg> M3\4NJJi\Gmxc3Xud4l1cXqnczDOV2NNSyClZXzsd{BqdiCjIIC1N{1l\XCnbnTlcpQhdWGwbnXy MmDKNlE4QTlyM{O=
H460 MUDBdI9xfG:|aYOgRZN{[Xl? MnHoNlAxKG6P NH:0SVcyKGh? MWHyZYRqd3OnboPpeIl7\XNiTmPDUGMh[2WubIOgbY4h[SCyNUOt[IVx\W6mZX70JI1idm6nch?= MmTpNlE4QTlyM{O=
H1299 MXnBdI9xfG:|aYOgRZN{[Xl? MVSyNFAhdk1? NY[3SIx1OSCq NWrZW3VnemGmaX;z[Y5{cXSrenXzJG5US0yFIHPlcIx{KGmwIHGgdFU{NWSncHXu[IVvfCCvYX7u[ZI> MljoNlE4QTlyM{O=
Calu-6  NEjSbYpCeG:ydH;zbZMhSXO|YYm= MYWyNFAhdk1? M2jwZVEhcA>? MlvIdoFlcW:|ZX7zbZRqgmW|IF7TR2xEKGOnbHzzJIlvKGFicEWzMYRmeGWwZHXueEBu[W6wZYK= MXmyNVc6QTB|Mx?=
WiDr MofmT4lv[XOnIFHzd4F6ew>? MXyxNE0yODByMDDuUS=> MkGyPEBp MnvQbY5pcWKrdIOgdIhwe3Cqb4L5cIF1cW:wIH;mJGNFSzJiYYSgWJlzOTVid3n0bEBidiCHQ{WwxsB3[Wy3ZTDv[kA5PSCwbX;sM2wheHKndILlZZRm\CC5aYToJIdmdWOrdHHibY5m NVHXUFdjOTl6OEe1OFU>

... 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 2年-20℃
6月-80℃in solvent
別名 N/A
溶解度 (25°C) * In vitro DMSO 80 mg/mL (159.8 mM)
0.0001 mg/mL (0.0 mM)
エタノール <1 mg/mL (<1 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)

技術サポート&よくある質問(FAQ)

ストックの作り方、阻害剤の保管する方法、細胞実験や動物実験に注意すべきな点を全部含めており、製品を取扱う時よくあった質問に対して取扱説明書でお答えいたします。

電話番号: +1-832-582-8158 Ext:3月曜日〜金曜日 9:00 AM–5:00 PM (米国中部標準時)

他の質問がある場合は、お気軽くお問合せください。

* 必須

Related Wee1 阻害剤

  • Ro-3306

    RO-3306 is an ATP-competitive, and selective CDK1 inhibitor with Ki of 20 nM, >15-fold selectivity against a diverse panel of human kinases.

  • CCG-1423

    CCG-1423 is a specific RhoA pathway inhibitor, which inhibits SRF-mediated transcription.

  • ML141

    ML141 is a potent, selective and reversible non-competitive inhibitor of Rho family GTPase cdc42 with IC50 of 200 nM.

  • Salirasib

    Salirasib is a potent competitive prenylated protein methyltransferase (PPMTase) inhibitor with Ki of 2.6 μM, which inhibits Ras methylation. Phase 2.

  • Y-27632 2HCl

    Y-27632 2HClはRho関連プロテインキナーゼ1(ROCK1、p160ROCK)選択阻害剤、Kiが140nMになる。

  • Palbociclib (PD-0332991) HCl

    Palbociclib (PD-0332991) HClはCdksを抑制、Cdk4/ cyclin D1とCdk6/ cyclin D2に作用する時、IC50がそれぞれ11と16nMになる。

    Features:Non-cytotoxic, and halts cancer cell growth & could be used in glioblastoma that has relapsed after temozolomide treatment (a chemotherapeutic used to treat many cancers).

  • Alisertib (MLN8237)

    Alisertib (MLN8237)は、1.2nMのIC50による選択的なオーロラA阻害剤です。

    Features:First orally available inhibitor of Aurora A.

  • Palbociclib (PD0332991) Isethionate

    Palbociclib (PD0332991) Isethionateは、非常に特定のCDK4CDK6の阻害剤で、 IC50 がそれぞれ11 nM と 16 nMです。

    Features:The 1st specific inhibitor for CDK4/6 to show promise in multiple cancers.

  • Dinaciclib (SCH727965)

    Dinaciclib(SCH727965)は、小説と強力なサイクリン依存的なキナーゼ阻害剤で、 CDK2、 CDK5、 CDK1、 CDK9 に作用すると、 IC50 がそれぞれ 1 nM、1 nM、 3 nM 、4 nMになる。

最近チェックしたアイテム

Tags: MK-1775を買う | MK-1775供給者 | MK-1775を購入する | MK-1775費用 | MK-1775生産者 | オーダーMK-1775 | MK-1775代理店
×
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
お問い合わせ