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 MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXfsNmJwUUN3ME2xN{4zKMLzIEGuNUDPxE1? M1fnSVI2PDV6OUW0
BxPC-3 MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYDJR|UxRTBwODFCtUAxNjB|IN88US=> NV36T5REOjV2NUi5OVQ>
CFPAC-1 NYTuW4poT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnXDTWM2OD1|LkOgxtEhOC5{IN88US=> M3PtOlI2PDV6OUW0
HPAC M3\6Umdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXPkeJBEUUN3ME2wMlUhyrFiMD6wNUDPxE1? NFvwblUzPTR3OEm1OC=>
MIAPaCa-2 NWTXZnl1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUK2dohHUUN3ME2wMlUhyrFiMD6wOUDPxE1? NEDLRpczPTR3OEm1OC=>
PANC-1 NFrOeYNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mn2zTWM2OD1zMD62JOKyKDFwMTFOwG0> MXWyOVQ2QDl3NB?=
SK-N-BE (2) NGrOb29Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmPhTWM2OD1{LkVihKnDueLCiUCuN{DPxE1? M3eyOFI2OzB6OUG2
SK-N-BE (2), PAN→MK M1G5T2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkHRTWM2OD1{Nj625qCKyrIkgJm5MlYh|ryP M2HIZlI2OzB6OUG2
SK-N-BE (2), MK→PAN MX3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVHBd3BRUUN3ME2yMlTjiIoEsfMAjVAvOyEQvF2= MX6yOVMxQDlzNh?=
SK-N-AS MX3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4jwe2lEPTB;MD61NQKBkcLz4pEJNE4xOiEQvF2= M3zYPVI2OzB6OUG2
SK-N-DZ M{\m[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{HTbWlEPTB;MD6zOwKBkcLz4pEJNE4xOSEQvF2= NYHoeoJ2OjV|MEi5NVY>
SK-N-AS MnT2RZBweHSxc3nzJGF{e2G7 NHnQWoQ2ODBibl2= MUS0PEBp M4rCbolv\HWlZYOgZ4VtdCCjcH;weI9{cXN? NFTMblYzPTNyOEmxOi=>
SK-N-DZ MXLBdI9xfG:|aYOgRZN{[Xl? M3j2elUxOCCwTR?= NFzyW3Y1QCCq Mn3UbY5lfWOnczDj[YxtKGGyb4D0c5Nqew>? NF:2NXUzPTNyOEmxOi=>
THP-1 MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NY\YNVVvOTJ3L{K1NE82ODBibl2= NVyyXo5xPDhiaB?= MXzpcoNz\WG|ZYOgZ4VtdCCmZXH0bEBqdiCjIHPvcoNmdnS{YYTpc44u\GWyZX7k[Y51KG2jbn7ldi=> NUHlfZNNOjVyOES2NVQ>
MV4-11 MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHW0fGoyOjVxMkWwM|UxOCCwTR?= NVSwW5Z4PDhiaB?= MXfpcoNz\WG|ZYOgZ4VtdCCmZXH0bEBqdiCjIHPvcoNmdnS{YYTpc44u\GWyZX7k[Y51KG2jbn7ldi=> MUeyOVA5PDZzNB?=
U937 NXzrNIViT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVmyT4FFOTJ3L{K1NE82ODBibl2= NUnDepd6PDhiaB?= NYHlUZB7cW6lcnXhd4V{KGOnbHyg[IVifGhiaX6gZUBkd26lZX70doF1cW:wLXTldIVv\GWwdDDtZY5v\XJ? M2Lid|I2ODh2NkG0
HL-60 NYHLV|Z6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3rncFEzPS9{NUCvOVAxKG6P NVzV[3JXPDhiaB?= MkjrbY5kemWjc3XzJINmdGxiZHXheIghcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI> MmDxNlUxQDR4MUS=
OCI-AML3 NHPMT4lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWT6cY5TOTJ3L{K1NE82ODBibl2= NY\hVI95PDhiaB?= M1LuNolv[3KnYYPld{Bk\WyuIHTlZZRpKGmwIHGgZ49v[2WwdILheIlwdi2mZYDlcoRmdnRibXHucoVz NVX5cYt1OjVyOES2NVQ>
MOLM-13 MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGTEfFIyOjVxMkWwM|UxOCCwTR?= MmPHOFghcA>? NH3QWIRqdmO{ZXHz[ZMh[2WubDDk[YF1cCCrbjDhJINwdmOnboTyZZRqd25vZHXw[Y5l\W62IH3hco5meg>? M4LPelI2ODh2NkG0
CMK Mon0R4VtdCCYaXHibYxqfHliQYPzZZk> NEHo[o4yOC1zMECwNEBvVQ>? MYO3NkBp MorpdoVlfWOnczDj[YxtKH[rYXzpZol1gSCrbjDhJINwdmOnboTyZZRqd25vZHXw[Y5l\W62IH3hco5meg>? M{jucVI1QTZ{M{Ox
CMY NGHqOlVE\WyuIG\pZYJqdGm2eTDBd5NigQ>? NGPBS2syOC1zMECwNEBvVQ>? NHLxZZU4OiCq NV3je|Y6emWmdXPld{Bk\WyuII\pZYxq[mm2eTDpckBiKGOxbnPlcpRz[XSrb36t[IVx\W6mZX70JI1idm6nch?= MXGyOFk3OjN|MR?=
Dayo NFPv[XNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmXtTWM2OD1zNUCgcm0> NUfBdo9ROjR4NkG5NVA>
UW228 MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYTJR|UxRTJ|MjDuUS=> MV[yOFY3OTlzMB?=
IST-MES1 MUfD[YxtKF[rYXLpcIl1gSCDc4PhfS=> MmfENVUxNzJ3MDDuUS=> MmnnO|IhcA>? M3G5bYVvcGGwY3XzJJRp\SClaYPwcIF1cW5iY4n0c5RwgGmlIHXm[oVkfCCrbjDhJINwdmOnboTyZZRqd25vZHXw[Y5l\W62IH3hco5meg>? MXSyOFM3PTd6Mh?=
IST-MES2 Mn:1R4VtdCCYaXHibYxqfHliQYPzZZk> NV7XS2Y6OTVyL{K1NEBvVQ>? NETVZ3A4OiCq MXLlcohidmOnczD0bIUh[2m|cHzheIlvKGO7dH;0c5hq[yCnZn\lZ5QhcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI> NHPBUGwzPDN4NUe4Ni=>
REN MYfD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NFS3UWoyPTBxMkWwJI5O MknWO|IhcA>? NVrwZ4Fv\W6qYX7j[ZMhfGinIHPpd5Bt[XSrbjDjfZRwfG:6aXOg[YZn\WO2IHnuJIEh[2:wY3XueJJifGmxbj3k[ZBmdmSnboSgcYFvdmW{ MXyyOFM3PTd6Mh?=
NCI-H2452 NWi4eHE6S2WubDDWbYFjcWyrdImgRZN{[Xl? M3zhTVE2OC9{NUCgcm0> MkHwO|IhcA>? NWnCOnF{\W6qYX7j[ZMhfGinIHPpd5Bt[XSrbjDjfZRwfG:6aXOg[YZn\WO2IHnuJIEh[2:wY3XueJJifGmxbj3k[ZBmdmSnboSgcYFvdmW{ NEHrW2UzPDN4NUe4Ni=>
MSTO-211H NYi2d2w1S2WubDDWbYFjcWyrdImgRZN{[Xl? NXftSmdGOTVyL{K1NEBvVQ>? NIDsPHE4OiCq M{\1NIVvcGGwY3XzJJRp\SClaYPwcIF1cW5iY4n0c5RwgGmlIHXm[oVkfCCrbjDhJINwdmOnboTyZZRqd25vZHXw[Y5l\W62IH3hco5meg>? MY[yOFM3PTd6Mh?=
NCI-H2052 MnuzR4VtdCCYaXHibYxqfHliQYPzZZk> NHLvbJcyPTBxMkWwJI5O MWq3NkBp MYjlcohidmOnczD0bIUh[2m|cHzheIlvKGO7dH;0c5hq[yCnZn\lZ5QhcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI> NWroOIhSOjR|NkW3PFI>
WEE1 NFvE[ItIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGO0SpVKSzVyPUWuNkBvVQ>? NHLwdmgzOzZ7OU[1OS=>
CDC2 NVXMOnBZT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXzjeXBDUUN3MP-8olExODBibl2= MVSyN|Y6QTZ3NR?=
CDK7 NVXUNZdiT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M17TdGlEPTExvK6xNFAxKG6P MlPlNlM3QTl4NUW=
MYT1 MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NF;GcmpKSzVyPUWzNEBvVQ>? MnG3NlM3QTl4NUW=
T98G  M17CNmFxd3C2b4Ppd{BCe3OjeR?= MlPxNVAxNzJ3MDDuUS=> M2\vUlYhcA>? NX;EZlB{\W6qYX7j[ZMhemGmaXH0bY9vNWmwZIXj[YQh[2WubDDrbYxtcW6p MWqyNVk6Ojd7Mx?=
A549 Ml3GRZBweHSxc3nzJGF{e2G7 NHzoeokzODBibl2= NH\VeYQyKGh? M4jFNZJi\Gmxc3Xud4l1cXqnczDOV2NNSyClZXzsd{BqdiCjIIC1N{1l\XCnbnTlcpQhdWGwbnXy NG[3NmMzOTd7OUCzNy=>
H460 NGPuRpFCeG:ydH;zbZMhSXO|YYm= MknBNlAxKG6P MknNNUBp MYPyZYRqd3OnboPpeIl7\XNiTmPDUGMh[2WubIOgbY4h[SCyNUOt[IVx\W6mZX70JI1idm6nch?= MlnGNlE4QTlyM{O=
H1299 NIPtOIhCeG:ydH;zbZMhSXO|YYm= Mm\rNlAxKG6P NEnlNIgyKGh? MX;yZYRqd3OnboPpeIl7\XNiTmPDUGMh[2WubIOgbY4h[SCyNUOt[IVx\W6mZX70JI1idm6nch?= NUnGbFdtOjF5OUmwN|M>
Calu-6  NUfLe3NLSXCxcITvd4l{KEG|c3H5 MoS2NlAxKG6P M4L1bFEhcA>? NX[0eWxoemGmaX;z[Y5{cXSrenXzJG5US0yFIHPlcIx{KGmwIHGgdFU{NWSncHXu[IVvfCCvYX7u[ZI> Mn;6NlE4QTlyM{O=
WiDr NX24PZJZU2mwYYPlJGF{e2G7cx?= MlK3NVAuOTByMECgcm0> NXiye3N2QCCq MnLubY5pcWKrdIOgdIhwe3Cqb4L5cIF1cW:wIH;mJGNFSzJiYYSgWJlzOTVid3n0bEBidiCHQ{WwxsB3[Wy3ZTDv[kA5PSCwbX;sM2wheHKndILlZZRm\CC5aYToJIdmdWOrdHHibY5m NGjvWYYyQTh6N{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 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 (8)

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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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