MK-8776 (SCH 900776) 化学構造
分子量: 376.25

高品質保証

カスタマーフィードバック(1)

Quality Control & MSDS

製品説明

  • Compare Chk Inhibitors
    Chk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-8776 (SCH 900776)は、選択的なChk1</b> 阻害剤で、IC50 が 3 nMです。
ターゲット Chk1
IC50 3 nM [1]
In vitro試験 SCH 900776 is a less potent inhibitor of Chk2 and CDK2 with IC50 of 1.5 μM and 0.16 μM, respectively. SCH 900776 shows no significant inhibition of cytochrome P450 human liver microsomal isoforms 1A2, 2C9, 2C19, 2D6, and 3A4. SCH 900776 induces a dose-dependent loss of DNA replication capability 24 hours after hydroxyurea exposure. SCH 900776 enhances the γ-H2AX response of hydroxyurea, 5-fluoruracil, and cytarabine. In combination with an antimetabolite, SCH 900776 induces accumulation of γ-H2AX within 2 hours, indicative of replication fork collapse and double stranded DNA breaks. Additionally, SCH 900776 suppresses accumulation of the Chk1 pS296 autophosphorylation in a dose-dependent manner. Exposure of proliferating WS1 cells to SCH 900776 is associated with rapid, dose-dependent accumulation of Chk1 pS345, indicating that cycling populations of normal cells induce Chk1 pS345 following exposure to SCH 900776 as part of a futile cycle, perhaps driven by AT-family kinases and DNA-PK.[1]
Cell Data
Cell LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
U251 Ml7vS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2LtNFIxOC9{MECwJI5O NXe0NHZIOjRiaB?= M3vPPYRm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= NUPuNGxCOjR|NUm1NlY>
HCT115 NWO4V|d4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFzwW5kzODBxMkCwNEBvVQ>? NGrOe5IzPCCq NFfsSZVl\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= NUTic5k3OjR|NUm1NlY>
SW620 MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MY[yNFAwOjByMDDuUS=> NX;Oenp{OjRiaB?= NIL6NmVl\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= NWXG[pZpOjR|NUm1NlY>
IGROV-1 M3frVmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXyyNFAwOjByMDDuUS=> NIfLbVQzPCCq NIrVbZll\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= MmS0NlQ{PTl3Mk[=
HCT116 M124WWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlzrNlAxNzJyMECgcm0> NV\tOFkxOjRiaB?= NX\Hc4Jb\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l M1HlcFI1OzV7NUK2
MCF10A NVrOXYVYT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MofFNlAxNzJyMECgcm0> MYmyOEBp MUXk[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? M3vBXVI1OzV7NUK2
MiaPaCa-2 NF\FZ|dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkjINlAxNzJyMECgcm0> NIPMfG4zPCCq Mnv6[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n NE\lWpAzPDN3OUWyOi=>
MDA-MB-231 NW\Ub3FTT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUeyNFAwOjByMDDuUS=> NYDMZVV2OjRiaB?= NF\aeJBl\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= NXq5[XhWOjR|NUm1NlY>
HCC2998 M4fF[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Ml:zNlAxNzJyMECgcm0> M{\0XFI1KGh? MmH1[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n NYjpfYZCOjR|NUm1NlY>
U87 MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NV\XOoxIOjByL{KwNFAhdk1? M4C3UFI1KGh? M3jSSoRm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= NGC5UYIzPDN3OUWyOi=>
MDA-MB-435 MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1;BOVIxOC9{MECwJI5O NYDJXWFWOjRiaB?= MX3k[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? NEn1Z|kzPDN3OUWyOi=>
SNB19 NHq2T3ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHvLXHAzODBxMkCwNEBvVQ>? MVmyOEBp NVLpXmFw\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l MUSyOFM2QTV{Nh?=
U20S NHrveHlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVfMeo9NOjByL{KwNFAhdk1? MmHPNlQhcA>? M1HYdoRm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= M{L2U|I1OzV7NUK2
A498 NEPaVWhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmPrNlAxNzJyMECgcm0> NGj3bYszPCCq Mnzw[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n M1Ht[|I1OzV7NUK2
TK10 M4K2TGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkT6NlAxNzJyMECgcm0> M{nFbFI1KGh? NFHKUHZl\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= MXeyOFM2QTV{Nh?=
AsPC-1 M{XJTGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4XjSlIxOC9{MECwJI5O MXSyOEBp NWC5Oo1j\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l Ml;2NlQ{PTl3Mk[=
H23 MVnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIO1NWw2ODBibl2= NIfreZEzPCCq M2H3fmROW09? NIe1R3hmdmijbnPld{B1cGViY3jlcY9{\W6|aYTpfoF1cW:wIITvJHBOYA>? NFHjbFczPDFzM{W0PS=>
H1437 NXT1U29XT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWC1NFAhdk1? MmiyNlQhcA>? NXnx[mw6TE2VTx?= NYnNbXJX\W6qYX7j[ZMhfGinIHPo[Y1we2Wwc3n0bZpifGmxbjD0c{BRVVh? NYfDe|dkOjRzMUO1OFk>
H1993 NHjNPHFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlfMOVAxKG6P MU[yOEBp NYXT[lRwTE2VTx?= NFjudoZmdmijbnPld{B1cGViY3jlcY9{\W6|aYTpfoF1cW:wIITvJHBOYA>? NVHCZmxHOjRzMUO1OFk>
H1299 NInZZYdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1;FUlUxOCCwTR?= NVfMR2hbOjRiaB?= M1vUcGROW09? NVzrSnNn\W6qYX7j[ZMhfGinIHPo[Y1we2Wwc3n0bZpifGmxbjD0c{BRVVh? NVrac5dOOjRzMUO1OFk>
AsPC-1 MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYDBTFFmOTBvMUCwNEBvVQ>? MUmyOE01QGh? M17ZR4VvcGGwY3XzJJRp\SClaHXtc5NmdnOrdHn6ZZRqd25idH:g[4Vu[2m2YXLpcoU> NEPUbmwzOzhyNESyNi=>
MiaPaCa-2 NX;pSIw6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYLkZYN4OTBvMUCwNEBvVQ>? MWmyOE01QGh? MWflcohidmOnczD0bIUh[2inbX;z[Y5{cXSrenH0bY9vKHSxIHflcYNqfGGkaX7l NYjxNIR5OjN6MES0NlI>
BxPC-3 NFGz[GRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUSxNE0yODByIH7N MmHxNlQuPDiq NV3PdG9W\W6qYX7j[ZMhfGinIHPo[Y1we2Wwc3n0bZpifGmxbjD0c{Bo\W2laYThZolv\Q>? MnjHNlM5ODR2MkK=
SKOV3 M13sZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVewMlMhyrWP NIDkRng5KGR? NIP0ZVd{\W6|aYTpfoV{KHSqZTDj[YxtKGyrbnXzJJRwKGenbXPpeIFjcW6nwrC= MnXYNlM2PDh{Nkm=
OVCAR-8 NWDSZVMzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3P3VFAvOyEEtV2= NIfpT|E5KGR? M3\jfJNmdnOrdHn6[ZMhfGinIHPlcIwhdGmwZYOgeI8h\2WvY3n0ZYJqdmYEoB?= MoS5NlM2PDh{Nkm=
MV-4-11 NXfHVoUySXCxcITvd4l{KEG|c3H5 MorMNVAxNTdyMDDuUS=> NYTaNIVlPDhiaB?= M3\hO4lv\HWlZYOgZZBweHSxc3nzJIRwe2ViZHXw[Y5l\W62bIm= Mn[yNlM2OzZ5MkG=
U937 MVLBdI9xfG:|aYOgRZN{[Xl? MlK5NVAxNTdyMDDuUS=> MV:0PEBp NITxVoxqdmS3Y3XzJIFxd3C2b4Ppd{Bld3OnIHTldIVv\GWwdHz5 MmXBNlM2OzZ5MkG=
MOLM-13  M4jaU2Fxd3C2b4Ppd{BCe3OjeR?= M2DET|ExOC15MECgcm0> NHLVV4s1QCCq M3\iW4lv\HWlZYOgZZBweHSxc3nzJIRwe2ViZHXw[Y5l\W62bIm= M1;3R|I{PTN4N{Kx
A2058  NX3GVlJyS2WubDDWbYFjcWyrdImgRZN{[Xl? MnzTN|cvPS1|MECgcm0> MlS3O|IhcA>? NHjQ[ldFVVOR MlHqdoVlfWOnczD0bIUhVUtvMUe3OUBGSzVywrDifUA2NW[xbHSgeI8h[W5iYY\ldoFo\SCxZjC0OUBvVQ>? MWCyN|E1QDZ6NB?=
H2009 NWHQ[mtXS2WubDDWbYFjcWyrdImgRZN{[Xl? MUC1NFAhdk1? M1LQVVczKGh? MUnEUXNQ MULy[ZN2dHS|IHnuJGcyN1NvcHjhd4Uh[WOldX31cIF1cW:wIHPvcYJqdmWmIIfpeIghVUtvMUe3OS=> M3;OZlI{OTR6Nki0
Su.86.86 MmfnR4VtdCCYaXHibYxqfHliQYPzZZk> MkO0OVAxKG6P M1XmU|czKGh? NU\HdnpTTE2VTx?= MYry[ZN2dHS|IHnuJGcyN1NvcHjhd4Uh[WOldX31cIF1cW:wIHPvcYJqdmWmIIfpeIghVUtvMUe3OS=> MlvVNlMyPDh4OES=
HRE MXvD[YxtKF[rYXLpcIl1gSCDc4PhfS=> MVO1NFAhdk1? MlPSO|IhcA>? NHLVcXpFVVOR Mk\3doV{fWy2czDpckBIOS:VLYDoZZNmKGGlY4XteYxifGmxbjDjc41jcW6nZDD3bZRpKE2NLUG3O|U> NHj0cpMzOzF2OE[4OC=>
HMEC MV3D[YxtKF[rYXLpcIl1gSCDc4PhfS=> MkLLOVAxKG6P MVW3NkBp MnfpSG1UVw>? MnvXdoV{fWy2czDpckBIOS:VLYDoZZNmKGGlY4XteYxifGmxbjDjc41jcW6nZDD3bZRpKE2NLUG3O|U> NILtUWMzOzF2OE[4OC=>
U2OS  MoniSpVv[3Srb36gRZN{[Xl? NGfWfnkzKML3TR?= M3;wWVAuOjRiaB?= MYfpcoR2[2W|IIDoc5NxcG:{eXzheIlwdiCxZjDDbIsyKGG2IIPldolv\SB|NEWgZZQh[m:2aDDjc45k\W62cnH0bY9veyCjczDlZZJtgSCjczCyJIgh[W[2ZYKgZYRucW6rc4TyZZRqd25? MljiNlI6OzdzNEe=
U2OS  NYriTVR{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYi2SmVJOC1zMDFCuW0> NXzj[2kzOjRxNEigbC=> MXPpcohq[mm2czDj[YxtKGe{b4f0bEBld3OnIHTldIVv\GWwdHz5 Mne4NlI6OzdzNEe=
U937 NUXPT4szTnWwY4Tpc44hSXO|YYm= MUmxNFAuPTByIH7N NEnXb4g1KGkEoB?= NYH6OVM4\GWlcnXhd4V{KHSqZTDjfZRiemGkaX7lMYlv\HWlZXSgR4hsOSCjdYTvdIhwe3Cqb4L5cIF1cW:wIHH0JHNmejJ7NtMgZY5lKHC{ZY\lcpR{KEOmY{K1RUBld3ewcnXneYxifGmxbh?= M4PnOFIzQDZ7OE[5
U937 NF25cVlHfW6ldHnvckBCe3OjeR?= MV:xNFAhdk1? M120PFQhcMLi M1vPV5JmfmW{c3XzJJRp\SCleYThdoFjcW6nLXnu[JVk\WRiaX7obYJqfGmxbjDv[uKhO0hvdHj5cYllcW6nIHnuZ49zeG:{YYTpc44hcW62bzDEUmE> MnLlNlI5Pjl6Nkm=
U937 NH33XY1HfW6ldHnvckBCe3OjeR?= NV62NpZ1OTByLUWwNEBvVQ>? NUnzU4dXPCCqwrC= Mk\LbY5lfWOnczDpcoNz\WG|ZXSgdIhwe3Cqb4L5cIF1cW:wIH;mJGgzSVh? MlXmNlI5Pjl6Nkm=
HL-60 NEfuNo1CeG:ydH;zbZMhSXO|YYm= M3L0PVMxNzFyMD:zNFAhdk1? MU[yOEBp NF\jXm5FVVOR M4DlfIVvcGGwY3XzJIN6fGG{YXLpcoUucW6mdXPl[EBieG:ydH;zbZM> NFnIblAzOjh4OUi2PS=>
ML-1 NETaSVFCeG:ydH;zbZMhSXO|YYm= M3riSlI2NzVyL{GwNEBvVQ>? NHjp[YMzPCCq MnzpSG1UVw>? M3LIXYVvcGGwY3XzJIN6fGG{YXLpcoUucW6mdXPl[EBieG:ydH;zbZM> NXrISZNkOjJ6Nkm4Olk>
HCT116 NELYOFFHfW6ldHnvckBCe3OjeR?= MX:xJOK2VQ>? M33qT|I1KGh? M4jXO4Fjem:pYYTld{Bw\iClZXzsJIN6[2ynIHHydoV{fMLi NWG5UG02OjJ3MUC1OlA>
U2OS M1T3dmZ2dmO2aX;uJGF{e2G7 M1\oRVEhyrWP NHTUXGszPCCq MonEZYJzd2ejdHXzJI9nKGOnbHygZ5lkdGViYYLy[ZN1yqB? MYGyNlUyODV4MB?=

... Click to View More Cell Line Experimental Data

In vivo試験 Administered 30 minutes after gemcitabine, 4 mg/kg SCH 900776 is sufficient to induce the γ-H2AX biomarker while 8 mg/kg leads to enhanced tumor pharmacodynamic and regression responses relative to gemcitabine or SCH 900776 alone. Dose escalation of SCH 900776 (16 mg/kg and 32 mg/kg) induces incremental improvements in tumor response. Importantly, doses of SCH 900776 associate with robust biomarker activation and improved tumor response are not associated with enhanced toxicity of gemcitabine on hematological parameters in BALB/c mice. [1]
臨床試験 A Phase I study of SCH 900776 with and without Gemcitabine in patients with solid tumors or lymphoma has been completed.
特集

プロトコル (参考用のみ)

キナーゼアッセイ: [1]

Chk1 SPA assay An in vitro assay utilizing recombinant His-Chk1 expressed in the baculovirus expression system as an enzyme source and biotinylated peptide based upon CDC25C as substrate. His-Chk1 is diluted to 32 nM in kinase buffer containing 50 mM Tris pH 8.0, 10 mM MgCl2, and 1 mM DTT. CDC25C (CDC25 Ser216 C-term biotinylated peptide) peptide is diluted to 1.93 μM in kinase buffer. For each kinase reaction, 20 μL of 32 nM Chk1 enzyme solution and 20 μL of 1.926 μM CDC25C are mixed and combined with 10 μL of SCH 900776 diluted in 10% DMSO, making final reaction concentrations of 6.2 nM Chk1, 385 nM CDC25C and 1% DMSO after addition of start solution. The reaction is started by addition of 50 μL of start solution consisting of 2 μM ATP and 0.2 μCi of 33P-ATP, making a final reaction concentration of 1 μM ATP, with 0.2 μCi of 33P-ATP per reaction. Kinase reactions run for 2 hours at room temperature and are stopped by the addition of 100 μL of stop solution consisting of 2 M NaCl, 1% H3PO4, and 5 mg/mL Streptavidin-coated SPA beads. SPA beads are captured using a 96-well GF/B filter plate and a Filtermate universal harvester. Beads are washed twice with 2 M NaCl and twice with 2 M NaCl with 1% phosphoric acid. Signal is then assayed using a TopCount 96-well liquid scintillation counter. Dose-response curves are generated from duplicate 8 point serial dilutions of SCH 900776. IC50 values are derived by nonlinear regression analysis.

動物実験: [1]

動物モデル Female nude mice injected subcutaneously with A2780 or MiaPaCa2 cells
製剤 Formulated in 20% hydroxypropyl β-cyclodextrin
投薬量 ~50 mg/kg
投与方法 Administered intraperitoneally

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-8776 (SCH 900776) SDF
分子量 376.25
化学式

C15H18BrN7

CAS No. 891494-63-6
保管 2年-20℃
6月-80℃in solvent
別名 N/A
溶解度 (25°C) * In vitro DMSO 3 mg/mL (7.97 mM)
<1 mg/mL (<1 mM)
エタノール <1 mg/mL (<1 mM)
In vivo 4% DMSO+30% propylene glycol 5 mg/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 6-bromo-3-(1-methyl-1H-pyrazol-4-yl)-5-((R)-piperidin-3-yl)pyrazolo[1,5-a]pyrimidin-7-amine

Frequently Asked Questions

  • Question 1
    I would like to know whether your product S2735 is the optically pure R enantiomer or whether it is a racemic mix.

    Answer: Our S2735 MK-8776 (SCH 900776) is R enantiomer.

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 Chk 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.

  • AZD7762

    AZD7762は、それぞれ小説(CHK1とCHK2のための5と<10nMのIC50値によるチェックポイント・キナーゼ阻害剤)です。

  • LY2603618

    LY2603618は、選択的なChk1</b> 潜在的抗腫瘍活性による阻害剤です。

  • CHIR-124

    CHIR-124は、0.3nMのIC50による新しくて強力なChk1阻害剤です。

  • PF-477736

    PF-477736 はChK 阻害剤、 ChK1、ChK2、VEGFR2、Yes と Fms に作用すると、IC50 がそれぞれ 0.49 nM、47 nM、 8 nM、 14 nM と 10 nMです。

  • 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。

最近チェックしたアイテム

Tags: MK-8776 (SCH 900776)を買う | MK-8776 (SCH 900776)供給者 | MK-8776 (SCH 900776)を購入する | MK-8776 (SCH 900776)費用 | MK-8776 (SCH 900776)生産者 | オーダーMK-8776 (SCH 900776) | MK-8776 (SCH 900776)代理店
×
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID