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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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 NV\YbIRtT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVWyNFAwOjByMDDuUS=> MnnTNlQhcA>? M{LaToRm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= M1fwZ|I1OzV7NUK2
HCT115 MlrrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4\NfFIxOC9{MECwJI5O NGLR[4czPCCq MVvk[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? NWPlWnlEOjR|NUm1NlY>
SW620 NXr0cJJ4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXTpTW5iOjByL{KwNFAhdk1? NEnON24zPCCq MVfk[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? NYX6flFyOjR|NUm1NlY>
IGROV-1 NIHseVBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NH3ZU2EzODBxMkCwNEBvVQ>? MkPLNlQhcA>? Moi0[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n MmjENlQ{PTl3Mk[=
HCT116 NEjyfpdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2X3clIxOC9{MECwJI5O MWqyOEBp M2OzWIRm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= MofXNlQ{PTl3Mk[=
MCF10A M{LkSmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlvoNlAxNzJyMECgcm0> NX;XXotMOjRiaB?= MmL1[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n MVeyOFM2QTV{Nh?=
MiaPaCa-2 NGTwNo1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnLLNlAxNzJyMECgcm0> NWm3NYdzOjRiaB?= NEL1Tmxl\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= NGnIPIIzPDN3OUWyOi=>
MDA-MB-231 MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGe5TWYzODBxMkCwNEBvVQ>? M2Ppe|I1KGh? NW\nWG5Y\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l MmfTNlQ{PTl3Mk[=
HCC2998 NHfMU3JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlrjNlAxNzJyMECgcm0> M4PNV|I1KGh? MWTk[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? MXGyOFM2QTV{Nh?=
U87 MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHnvWWEzODBxMkCwNEBvVQ>? MlOyNlQhcA>? NXTuT40x\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l NHnTV|AzPDN3OUWyOi=>
MDA-MB-435 M2rFfmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmjRNlAxNzJyMECgcm0> NHjRVowzPCCq NYX6[3k1\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l M3PGe|I1OzV7NUK2
SNB19 NVfOXHVOT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUGyNFAwOjByMDDuUS=> MnrBNlQhcA>? NUTVSXJx\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l MYWyOFM2QTV{Nh?=
U20S NXSzSZJ3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3L1WFIxOC9{MECwJI5O MUSyOEBp NIP1Z5hl\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= NFLtO20zPDN3OUWyOi=>
A498 NGXm[ZhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MV2yNFAwOjByMDDuUS=> NYjPUFVXOjRiaB?= MXvk[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? NHfpWHgzPDN3OUWyOi=>
TK10 NWjhbGR1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH;rNpkzODBxMkCwNEBvVQ>? MXqyOEBp Mojh[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n MmrZNlQ{PTl3Mk[=
AsPC-1 NV7XVGdHT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1W3fVIxOC9{MECwJI5O MXSyOEBp NF3CUY9l\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= NIe3fHMzPDN3OUWyOi=>
H23 Mof0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NE\DPIw2ODBibl2= Mm[2NlQhcA>? MV7EUXNQ M3jSUoVvcGGwY3XzJJRp\SClaHXtc5NmdnOrdHn6ZZRqd25idH:gVG1Z MUWyOFEyOzV2OR?=
H1437 M4W4XGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MX[1NFAhdk1? NVPROVFGOjRiaB?= MnfKSG1UVw>? M{OzSoVvcGGwY3XzJJRp\SClaHXtc5NmdnOrdHn6ZZRqd25idH:gVG1Z NH3kXHAzPDFzM{W0PS=>
H1993 MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYi1NFAhdk1? MnHsNlQhcA>? NYnP[JBxTE2VTx?= MVzlcohidmOnczD0bIUh[2inbX;z[Y5{cXSrenH0bY9vKHSxIGDNXC=> MVuyOFEyOzV2OR?=
H1299 NUPmUY1MT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYe1NFAhdk1? M1\uVlI1KGh? MkWzSG1UVw>? NFy1[VZmdmijbnPld{B1cGViY3jlcY9{\W6|aYTpfoF1cW:wIITvJHBOYA>? NX3EV3hGOjRzMUO1OFk>
AsPC-1 NUPv[4VuT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWfYSJduOTBvMUCwNEBvVQ>? MmO2NlQuPDiq MoXV[Y5p[W6lZYOgeIhmKGOqZX3vd4Vve2m2aYrheIlwdiC2bzDn[Y1kcXSjYnnu[S=> M3:xflI{QDB2NEKy
MiaPaCa-2 NULPe2dXT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYexNE0yODByIH7N MXyyOE01QGh? MYHlcohidmOnczD0bIUh[2inbX;z[Y5{cXSrenH0bY9vKHSxIHflcYNqfGGkaX7l NFXITVkzOzhyNESyNi=>
BxPC-3 NFf0VIRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M37FeVExNTFyMECgcm0> NIL4bGszPC12OHi= M3y5WIVvcGGwY3XzJJRp\SClaHXtc5NmdnOrdHn6ZZRqd25idH:g[4Vu[2m2YXLpcoU> M4\jclI{QDB2NEKy
SKOV3 MkTDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYCwMlMhyrWP M3Xid|gh\A>? MYfz[Y5{cXSrenXzJJRp\SClZXzsJIxqdmW|IITvJIdmdWOrdHHibY5myqB? NEWzfWgzOzV2OEK2PS=>
OVCAR-8 NUjRZm9oT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFLMbZIxNjNiwsXN MojzPEBl NVzweJVue2Wwc3n0bZpmeyC2aHWgZ4VtdCCuaX7ld{B1dyCpZX3jbZRi[mmwZdMg MUCyN|U1QDJ4OR?=
MV-4-11 NIrWW25CeG:ydH;zbZMhSXO|YYm= Mn7aNVAxNTdyMDDuUS=> NFjqXJM1QCCq NYOwbFQzcW6mdXPld{BieG:ydH;zbZMh\G:|ZTDk[ZBmdmSnboTsfS=> NHj4eHczOzV|NkeyNS=>
U937 M{fON2Fxd3C2b4Ppd{BCe3OjeR?= M{XXRlExOC15MECgcm0> NVPvcVhQPDhiaB?= NFv0NoRqdmS3Y3XzJIFxd3C2b4Ppd{Bld3OnIHTldIVv\GWwdHz5 M2D0RVI{PTN4N{Kx
MOLM-13  NEPQbo1CeG:ydH;zbZMhSXO|YYm= M1HGfFExOC15MECgcm0> NVzR[G5jPDhiaB?= MXXpcoR2[2W|IHHwc5B1d3OrczDkc5NmKGSncHXu[IVvfGy7 M1jHVFI{PTN4N{Kx
A2058  NVLBV5JmS2WubDDWbYFjcWyrdImgRZN{[Xl? Mni0N|cvPS1|MECgcm0> M2DHcFczKGh? M1fUOmROW09? MV3y[YR2[2W|IITo[UBOUy1zN{e1JGVEPTEEoHL5JFUu\m:uZDD0c{BidiCjdnXyZYdmKG:oIES1JI5O M2jZOFI{OTR6Nki0
H2009 MXnD[YxtKF[rYXLpcIl1gSCDc4PhfS=> M1Xq[VUxOCCwTR?= MUe3NkBp NHjQfGNFVVOR MlP1doV{fWy2czDpckBIOS:VLYDoZZNmKGGlY4XteYxifGmxbjDjc41jcW6nZDD3bZRpKE2NLUG3O|U> MkTlNlMyPDh4OES=
Su.86.86 NXrqcmh2S2WubDDWbYFjcWyrdImgRZN{[Xl? MXm1NFAhdk1? NW\Zb4xIPzJiaB?= M4TxWmROW09? Mor3doV{fWy2czDpckBIOS:VLYDoZZNmKGGlY4XteYxifGmxbjDjc41jcW6nZDD3bZRpKE2NLUG3O|U> NFXRbmwzOzF2OE[4OC=>
HRE NVHsOmZrS2WubDDWbYFjcWyrdImgRZN{[Xl? M3\TTFUxOCCwTR?= Mo\iO|IhcA>? MVPEUXNQ M2X1bZJme3WudIOgbY4hTzFxUz3wbIF{\SCjY3P1cZVt[XSrb36gZ49u[mmwZXSge4l1cCCPSz2xO|c2 M1PWN|I{OTR6Nki0
HMEC MVXD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NFy4ZoI2ODBibl2= M{PlS|czKGh? NE\nbXBFVVOR NGjWVmpz\XO3bITzJIlvKEdzL2OtdIhie2ViYXPjeY12dGG2aX;uJINwdWKrbnXkJJdqfGhiTVutNVc4PQ>? Mn7aNlMyPDh4OES=
U2OS  MoPYSpVv[3Srb36gRZN{[Xl? MkHZNkDDvU1? MljjNE0zPCCq NYHzOlVNcW6mdXPld{BxcG:|cHjvdplt[XSrb36gc4YhS2itMTDheEB{\XKrbnWgN|Q2KGG2IHLveIgh[2:wY3XueJJifGmxboOgZZMh\WG{bImgZZMhOiCqIHHmeIVzKGGmbXnubZN1emG2aX;u Mlm4NlI6OzdzNEe=
U2OS  NFnENY1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVnmN3oyOC1zMDFCuW0> NGPlVHQzPC92ODDo NI\uRlRqdmirYnn0d{Bk\WyuIHfyc5d1cCCmb4PlJIRmeGWwZHXueIx6 MVqyNlk{PzF2Nx?=
U937 NY\Wc4RbTnWwY4Tpc44hSXO|YYm= MmOwNVAxNTVyMDDuUS=> MXK0JIjDqA>? MkDC[IVkemWjc3XzJJRp\SCleYThdoFjcW6nLXnu[JVk\WRiQ3jrNUBifXSxcHjvd5Bpd3K7bHH0bY9vKGG2IGPldlI6PsLiYX7kJJBz\X[nboTzJGNl[zJ3QTDkc5dvemWpdXzheIlwdg>? NXnzTGI6OjJ6Nkm4Olk>
U937 NEPxV5NHfW6ldHnvckBCe3OjeR?= NGjRPVkyODBibl2= MYq0JIjDqA>? NFfROItz\X[ncoPld{B1cGViY4n0ZZJi[mmwZT3pcoR2[2WmIHnubIljcXSrb36gc4bDqDOKLYTofY1q\GmwZTDpcoNwenCxcnH0bY9vKGmwdH:gSG5C NUDseIJ[OjJ6Nkm4Olk>
U937 NIH6UFlHfW6ldHnvckBCe3OjeR?= MV6xNFAuPTByIH7N NXzzb2E3PCCqwrC= NGHzPHRqdmS3Y3XzJIlv[3KnYYPl[EBxcG:|cHjvdplt[XSrb36gc4YhUDKDWB?= M2D2SFIzQDZ7OE[5
HL-60 NGPWV5FCeG:ydH;zbZMhSXO|YYm= NVnqW5NmOzBxMUCwM|MxOCCwTR?= NULUcmh3OjRiaB?= NYnCVWJJTE2VTx?= M33iZYVvcGGwY3XzJIN6fGG{YXLpcoUucW6mdXPl[EBieG:ydH;zbZM> MUGyNlg3QTh4OR?=
ML-1 MlmxRZBweHSxc3nzJGF{e2G7 M3jaV|I2NzVyL{GwNEBvVQ>? M3LyO|I1KGh? NEDCWGxFVVOR NHXaUHlmdmijbnPld{BkgXSjcnHibY5mNWmwZIXj[YQh[XCxcITvd4l{ MYeyNlg3QTh4OR?=
HCT116 MoLuSpVv[3Srb36gRZN{[Xl? M3zzSVEhyrWP NVLZfI9qOjRiaB?= MlzzZYJzd2ejdHXzJI9nKGOnbHygZ5lkdGViYYLy[ZN1yqB? Mm\oNlI2OTB3NkC=
U2OS MWfGeY5kfGmxbjDBd5NigQ>? NEfLTZQyKML3TR?= M3y5dVI1KGh? M2TVN4Fjem:pYYTld{Bw\iClZXzsJIN6[2ynIHHydoV{fMLi M13SWlIzPTFyNU[w

... 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