MK-8776 (SCH 900776) 化学構造
分子量: 376.25

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製品説明

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    Chk製品生物活性の比較
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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 Ml7kS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NH72dFczODBxMkCwNEBvVQ>? M3zFZ|I1KGh? M{\3boRm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= NHLRcYkzPDN3OUWyOi=>
HCT115 NVn4d3RzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWmyNFAwOjByMDDuUS=> NEjQO2MzPCCq Mnn0[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n M3X2N|I1OzV7NUK2
SW620 M1nSXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnL3NlAxNzJyMECgcm0> Mn\PNlQhcA>? MWPk[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? MkSyNlQ{PTl3Mk[=
IGROV-1 MmDvS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4DBb|IxOC9{MECwJI5O M4jTfVI1KGh? NH3EOYNl\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= MlO5NlQ{PTl3Mk[=
HCT116 NGTHUZVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWnye45wOjByL{KwNFAhdk1? NHPHWmozPCCq MoXa[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n MV2yOFM2QTV{Nh?=
MCF10A M1TDcWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MojjNlAxNzJyMECgcm0> NICxNIIzPCCq Mn3a[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n MYKyOFM2QTV{Nh?=
MiaPaCa-2 Moe3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHvVXIYzODBxMkCwNEBvVQ>? M3fGc|I1KGh? NXTqdZp4\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l MoPkNlQ{PTl3Mk[=
MDA-MB-231 M2K0OGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NH7BUlEzODBxMkCwNEBvVQ>? MmWzNlQhcA>? MX\k[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? MWCyOFM2QTV{Nh?=
HCC2998 M3O5Xmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3;VbVIxOC9{MECwJI5O MVuyOEBp M4TTdoRm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= M4XRZlI1OzV7NUK2
U87 MmfMS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXXSUFh1OjByL{KwNFAhdk1? MVSyOEBp NYTEfVJQ\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l M37xTFI1OzV7NUK2
MDA-MB-435 M2DO[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NV\qRZZpOjByL{KwNFAhdk1? MX[yOEBp MkLY[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n Ml\CNlQ{PTl3Mk[=
SNB19 NVu3WY03T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NV;xdXZ2OjByL{KwNFAhdk1? Mly5NlQhcA>? NXvjfWxO\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l NIfOV2czPDN3OUWyOi=>
U20S NWHSbplET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{DJOVIxOC9{MECwJI5O Mo\aNlQhcA>? NViwSHdF\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l MUiyOFM2QTV{Nh?=
A498 Mn;nS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWeyNFAwOjByMDDuUS=> NXj0bmFiOjRiaB?= NYnONnd6\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l Mmi5NlQ{PTl3Mk[=
TK10 NVu3b3RTT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4TWSVIxOC9{MECwJI5O MVmyOEBp MlPI[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n NXixVlYyOjR|NUm1NlY>
AsPC-1 NGfH[WZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFTR[|AzODBxMkCwNEBvVQ>? MnKzNlQhcA>? NFPUbY5l\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= Mk\jNlQ{PTl3Mk[=
H23 NFLzO3lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoT6OVAxKG6P MnS2NlQhcA>? M3TnWWROW09? NX;hVJJs\W6qYX7j[ZMhfGinIHPo[Y1we2Wwc3n0bZpifGmxbjD0c{BRVVh? MX:yOFEyOzV2OR?=
H1437 NWTFVFJmT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3:5cFUxOCCwTR?= MkDrNlQhcA>? M1;3WGROW09? MVjlcohidmOnczD0bIUh[2inbX;z[Y5{cXSrenH0bY9vKHSxIGDNXC=> MnH1NlQyOTN3NEm=
H1993 M3nld2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWO1NFAhdk1? MoHsNlQhcA>? MUHEUXNQ NXj6e4NM\W6qYX7j[ZMhfGinIHPo[Y1we2Wwc3n0bZpifGmxbjD0c{BRVVh? NUHYd2JwOjRzMUO1OFk>
H1299 NEDKXGVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYnER5ZGPTByIH7N M2\5NlI1KGh? Ml7ySG1UVw>? NYD1bnhx\W6qYX7j[ZMhfGinIHPo[Y1we2Wwc3n0bZpifGmxbjD0c{BRVVh? Mm[xNlQyOTN3NEm=
AsPC-1 MmPkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3nv[lExNTFyMECgcm0> MYiyOE01QGh? MkjV[Y5p[W6lZYOgeIhmKGOqZX3vd4Vve2m2aYrheIlwdiC2bzDn[Y1kcXSjYnnu[S=> NUHMcZNtOjN6MES0NlI>
MiaPaCa-2 MoK4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnLmNVAuOTByMDDuUS=> MY[yOE01QGh? NHz5Z|JmdmijbnPld{B1cGViY3jlcY9{\W6|aYTpfoF1cW:wIITvJIdmdWOrdHHibY5m NVq3V3hnOjN6MES0NlI>
BxPC-3 Mlv6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWTadJFyOTBvMUCwNEBvVQ>? NXT0Snh7OjRvNEjo NF7wXYtmdmijbnPld{B1cGViY3jlcY9{\W6|aYTpfoF1cW:wIITvJIdmdWOrdHHibY5m NXnOZ5JUOjN6MES0NlI>
SKOV3 NIq5[VRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWWwMlMhyrWP MkX3PEBl MVvz[Y5{cXSrenXzJJRp\SClZXzsJIxqdmW|IITvJIdmdWOrdHHibY5myqB? MX2yN|U1QDJ4OR?=
OVCAR-8 MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3XlfVAvOyEEtV2= NHO4bJY5KGR? MoD0d4Vve2m2aYrld{B1cGViY3XscEBtcW6nczD0c{Bo\W2laYThZolv\cLi NYPs[G41OjN3NEiyOlk>
MV-4-11 MoXPRZBweHSxc3nzJGF{e2G7 MUmxNFAuPzByIH7N M2HwSVQ5KGh? NYrXT|c2cW6mdXPld{BieG:ydH;zbZMh\G:|ZTDk[ZBmdmSnboTsfS=> M3;EVlI{PTN4N{Kx
U937 NELONZRCeG:ydH;zbZMhSXO|YYm= NEe0S2syODBvN{CwJI5O MUi0PEBp NWrD[3RpcW6mdXPld{BieG:ydH;zbZMh\G:|ZTDk[ZBmdmSnboTsfS=> MW[yN|U{Pjd{MR?=
MOLM-13  NEfCblRCeG:ydH;zbZMhSXO|YYm= MUOxNFAuPzByIH7N MWG0PEBp MnPEbY5lfWOnczDhdI9xfG:|aYOg[I9{\SCmZYDlcoRmdnSueR?= MlTENlM2OzZ5MkG=
A2058  MU\D[YxtKF[rYXLpcIl1gSCDc4PhfS=> MUCzO{42NTNyMDDuUS=> NGK0OJI4OiCq MnH5SG1UVw>? NE\xSYpz\WS3Y3XzJJRp\SCPSz2xO|c2KEWFNUFCpIJ6KDVvZn;s[EB1dyCjbjDheoVz[WenIH;mJFQ2KG6P NVjUfmI6OjNzNEi2PFQ>
H2009 NHjtXmxE\WyuIG\pZYJqdGm2eTDBd5NigQ>? NVGzVXFYPTByIH7N NXLwUY54PzJiaB?= NYfieFNLTE2VTx?= NHK2[VBz\XO3bITzJIlvKEdzL2OtdIhie2ViYXPjeY12dGG2aX;uJINwdWKrbnXkJJdqfGhiTVutNVc4PQ>? MVmyN|E1QDZ6NB?=
Su.86.86 MnLiR4VtdCCYaXHibYxqfHliQYPzZZk> NFvmdmo2ODBibl2= Mn25O|IhcA>? NUnwZlJSTE2VTx?= MnLydoV{fWy2czDpckBIOS:VLYDoZZNmKGGlY4XteYxifGmxbjDjc41jcW6nZDD3bZRpKE2NLUG3O|U> M2nUWVI{OTR6Nki0
HRE M3vYfGNmdGxiVnnhZoltcXS7IFHzd4F6 M{PqXlUxOCCwTR?= M1vHWlczKGh? M{HhdGROW09? MmjqdoV{fWy2czDpckBIOS:VLYDoZZNmKGGlY4XteYxifGmxbjDjc41jcW6nZDD3bZRpKE2NLUG3O|U> MojnNlMyPDh4OES=
HMEC MUDD[YxtKF[rYXLpcIl1gSCDc4PhfS=> M4LGPVUxOCCwTR?= M{\0PFczKGh? M2\sWmROW09? MVry[ZN2dHS|IHnuJGcyN1NvcHjhd4Uh[WOldX31cIF1cW:wIHPvcYJqdmWmIIfpeIghVUtvMUe3OS=> NFn4eJMzOzF2OE[4OC=>
U2OS  MVPGeY5kfGmxbjDBd5NigQ>? NWr2TG5UOiEEtV2= NICzOWoxNTJ2IHi= NWfzfIhncW6mdXPld{BxcG:|cHjvdplt[XSrb36gc4YhS2itMTDheEB{\XKrbnWgN|Q2KGG2IHLveIgh[2:wY3XueJJifGmxboOgZZMh\WG{bImgZZMhOiCqIHHmeIVzKGGmbXnubZN1emG2aX;u MVuyNlk{PzF2Nx?=
U2OS  NVTrN2dnT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFnW[pAxNTFyINM1US=> NFrIc2wzPC92ODDo NVyy[2lucW6qaXLpeJMh[2WubDDndo94fGhiZH;z[UBl\XCnbnTlcpRtgQ>? NYPNO5hEOjJ7M{exOFc>
U937 M2nIe2Z2dmO2aX;uJGF{e2G7 MXixNFAuPTByIH7N M1v3dlQhcMLi NHvscWdl\WO{ZXHz[ZMhfGinIHP5eIFz[WKrbnWtbY5lfWOnZDDDbIsyKGG3dH;wbI9{eGixconsZZRqd25iYYSgV4VzOjl4wrDhcoQheHKndnXueJMhS2SlMkXBJIRwf26{ZXf1cIF1cW:w NGC2cWUzOjh4OUi2PS=>
U937 M2rs[GZ2dmO2aX;uJGF{e2G7 M2LpTFExOCCwTR?= MVe0JIjDqA>? Mlr1doV3\XK|ZYOgeIhmKGO7dHHyZYJqdmVvaX7keYNm\CCrbnjpZol1cW:wIH;mxsA{UC22aIntbYRqdmViaX7jc5Jxd3KjdHnvckBqdnSxIFTORS=> MUOyNlg3QTh4OR?=
U937 MXPGeY5kfGmxbjDBd5NigQ>? MXuxNFAuPTByIH7N MmSwOEBpyqB? M4\tbolv\HWlZYOgbY5kemWjc3XkJJBpd3OyaH;yfYxifGmxbjDv[kBJOkG[ M4DO[lIzQDZ7OE[5
HL-60 MYnBdI9xfG:|aYOgRZN{[Xl? NVm1OIF3OzBxMUCwM|MxOCCwTR?= M4HuXlI1KGh? MnrPSG1UVw>? MorI[Y5p[W6lZYOgZ5l1[XKjYnnu[U1qdmS3Y3XkJIFxd3C2b4Ppdy=> MVeyNlg3QTh4OR?=
ML-1 NFjZPFNCeG:ydH;zbZMhSXO|YYm= NX\PTYJIOjVxNUCvNVAxKG6P NHHJWVQzPCCq M4jxUmROW09? MlW2[Y5p[W6lZYOgZ5l1[XKjYnnu[U1qdmS3Y3XkJIFxd3C2b4Ppdy=> M2PqZ|IzQDZ7OE[5
HCT116 MVrGeY5kfGmxbjDBd5NigQ>? MoXSNUDDvU1? NFnufVgzPCCq M3Xld4Fjem:pYYTld{Bw\iClZXzsJIN6[2ynIHHydoV{fMLi NEDFb44zOjVzMEW2NC=>
U2OS NVvDT|JjTnWwY4Tpc44hSXO|YYm= NFvJZ2kyKML3TR?= NFLiW4YzPCCq NGDQZWpi[nKxZ3H0[ZMhd2ZiY3XscEBkgWOuZTDhdpJme3UEoB?= NYTNOoFwOjJ3MUC1OlA>

... 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 3年-20℃
2年-80℃in solvent
別名 N/A
溶解度 (25°C) * In vitro DMSO 3 mg/mL (7.97 mM)
Water <1 mg/mL
Ethanol <1 mg/mL
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

文献中の引用 (1)

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。

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* 必須

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID