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 MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MknlNlAxNzJyMECgcm0> NIXpNpczPCCq NVn2NmlM\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l NFHOd28zPDN3OUWyOi=>
HCT115 NVPVZmZ3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH3iR2gzODBxMkCwNEBvVQ>? NXzuOnV5OjRiaB?= NITNSodl\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= M1LXSlI1OzV7NUK2
SW620 MnPkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYPtcllsOjByL{KwNFAhdk1? MXuyOEBp NGfENGll\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= NWmzNpZKOjR|NUm1NlY>
IGROV-1 MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYrJbY5pOjByL{KwNFAhdk1? NH7k[IczPCCq NWS1OJZr\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l MWmyOFM2QTV{Nh?=
HCT116 NVXEcpZ{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUCyNFAwOjByMDDuUS=> NUT0WpJ6OjRiaB?= NWLCd45x\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l MW[yOFM2QTV{Nh?=
MCF10A MkTQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mk\FNlAxNzJyMECgcm0> M1nNNFI1KGh? NHj2c29l\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= M3XpW|I1OzV7NUK2
MiaPaCa-2 MlTTS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWDpcmpCOjByL{KwNFAhdk1? M4jISFI1KGh? MVfk[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? MoHMNlQ{PTl3Mk[=
MDA-MB-231 NFvzfFZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1fDVVIxOC9{MECwJI5O MoewNlQhcA>? M1TidIRm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= NVnZOoN[OjR|NUm1NlY>
HCC2998 NVXlcJVPT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHH5UG8zODBxMkCwNEBvVQ>? NWfmUY9QOjRiaB?= NHrDZldl\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= NVqyRlRHOjR|NUm1NlY>
U87 NWD5NWhRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUXkfoNoOjByL{KwNFAhdk1? M1jXXFI1KGh? MYXk[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? MXuyOFM2QTV{Nh?=
MDA-MB-435 M3HW[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYWyNFAwOjByMDDuUS=> MoWyNlQhcA>? MVrk[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? MnHkNlQ{PTl3Mk[=
SNB19 NWrsd403T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MX6yNFAwOjByMDDuUS=> M336bFI1KGh? NWnufGoy\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l NXPYUHl[OjR|NUm1NlY>
U20S M13mVGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmWwNlAxNzJyMECgcm0> NIHQVIIzPCCq MXrk[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? NHLPeo0zPDN3OUWyOi=>
A498 M33sWGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFG3OHgzODBxMkCwNEBvVQ>? MXKyOEBp NVn3XFdb\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l MmTJNlQ{PTl3Mk[=
TK10 MlrKS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MU[yNFAwOjByMDDuUS=> MWGyOEBp M4fjVYRm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= NH64c4szPDN3OUWyOi=>
AsPC-1 MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1rne|IxOC9{MECwJI5O M{TzOFI1KGh? M1fjNYRm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= MViyOFM2QTV{Nh?=
H23 NXn4XIxvT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXHvTmlsPTByIH7N MlfwNlQhcA>? M4PVR2ROW09? MV\lcohidmOnczD0bIUh[2inbX;z[Y5{cXSrenH0bY9vKHSxIGDNXC=> NGTTOnMzPDFzM{W0PS=>
H1437 NEXsZ4dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4jSO|UxOCCwTR?= NWqwfndLOjRiaB?= MmC1SG1UVw>? MWnlcohidmOnczD0bIUh[2inbX;z[Y5{cXSrenH0bY9vKHSxIGDNXC=> MV2yOFEyOzV2OR?=
H1993 MX7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUTmZ|U3PTByIH7N M4HnWVI1KGh? M3rOOGROW09? MmjV[Y5p[W6lZYOgeIhmKGOqZX3vd4Vve2m2aYrheIlwdiC2bzDQUXg> NV;XXnhzOjRzMUO1OFk>
H1299 NEPQbmlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWLUSVZUPTByIH7N NGS4NYkzPCCq NEfqUY5FVVOR NGDCRVlmdmijbnPld{B1cGViY3jlcY9{\W6|aYTpfoF1cW:wIITvJHBOYA>? MXWyOFEyOzV2OR?=
AsPC-1 NWnwNHJGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYqxNE0yODByIH7N M1TQXVI1NTR6aB?= NXvsTVI1\W6qYX7j[ZMhfGinIHPo[Y1we2Wwc3n0bZpifGmxbjD0c{Bo\W2laYThZolv\Q>? M{[1fVI{QDB2NEKy
MiaPaCa-2 M1WyTGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NX7WbWhYOTBvMUCwNEBvVQ>? M1jmWFI1NTR6aB?= NV3BT5BM\W6qYX7j[ZMhfGinIHPo[Y1we2Wwc3n0bZpifGmxbjD0c{Bo\W2laYThZolv\Q>? NELwSWIzOzhyNESyNi=>
BxPC-3 NI\tdGlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFnK[mMyOC1zMECwJI5O MnzQNlQuPDiq Ml\w[Y5p[W6lZYOgeIhmKGOqZX3vd4Vve2m2aYrheIlwdiC2bzDn[Y1kcXSjYnnu[S=> M4GwOlI{QDB2NEKy
SKOV3 MkLwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NW\KVlV5OC5|INM1US=> MlPJPEBl MV3z[Y5{cXSrenXzJJRp\SClZXzsJIxqdmW|IITvJIdmdWOrdHHibY5myqB? MViyN|U1QDJ4OR?=
OVCAR-8 NVfWS4tzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHjYNlYxNjNiwsXN MkjmPEBl NUPueGQ4e2Wwc3n0bZpmeyC2aHWgZ4VtdCCuaX7ld{B1dyCpZX3jbZRi[mmwZdMg MWKyN|U1QDJ4OR?=
MV-4-11 MoD5RZBweHSxc3nzJGF{e2G7 M3HFb|ExOC15MECgcm0> MkPyOFghcA>? M{K2eIlv\HWlZYOgZZBweHSxc3nzJIRwe2ViZHXw[Y5l\W62bIm= M3LhN|I{PTN4N{Kx
U937 M13pU2Fxd3C2b4Ppd{BCe3OjeR?= MnLCNVAxNTdyMDDuUS=> MmO1OFghcA>? MnPobY5lfWOnczDhdI9xfG:|aYOg[I9{\SCmZYDlcoRmdnSueR?= M4[1VVI{PTN4N{Kx
MOLM-13  MYjBdI9xfG:|aYOgRZN{[Xl? NHvNclMyODBvN{CwJI5O NGnkblE1QCCq NGW2e2ZqdmS3Y3XzJIFxd3C2b4Ppd{Bld3OnIHTldIVv\GWwdHz5 M3zMTFI{PTN4N{Kx
A2058  MVHD[YxtKF[rYXLpcIl1gSCDc4PhfS=> M{G4[VM4NjVvM{CwJI5O M3vFNFczKGh? M4\sRmROW09? MmfsdoVlfWOnczD0bIUhVUtvMUe3OUBGSzVywrDifUA2NW[xbHSgeI8h[W5iYY\ldoFo\SCxZjC0OUBvVQ>? NHLUVpAzOzF2OE[4OC=>
H2009 MkP0R4VtdCCYaXHibYxqfHliQYPzZZk> M1\RS|UxOCCwTR?= MX23NkBp MULEUXNQ NWj4XmhKemW|dXz0d{BqdiCJMT;TMZBp[XOnIHHjZ5VufWyjdHnvckBkd22kaX7l[EB4cXSqIF3LMVE4PzV? MYKyN|E1QDZ6NB?=
Su.86.86 NHyxd25E\WyuIG\pZYJqdGm2eTDBd5NigQ>? NEjOWoc2ODBibl2= M2f2PFczKGh? M2S5VmROW09? M3GyWZJme3WudIOgbY4hTzFxUz3wbIF{\SCjY3P1cZVt[XSrb36gZ49u[mmwZXSge4l1cCCPSz2xO|c2 NWf4N|ZtOjNzNEi2PFQ>
HRE MX\D[YxtKF[rYXLpcIl1gSCDc4PhfS=> NHrkU4g2ODBibl2= MkfhO|IhcA>? NGLLdotFVVOR NES0c5Nz\XO3bITzJIlvKEdzL2OtdIhie2ViYXPjeY12dGG2aX;uJINwdWKrbnXkJJdqfGhiTVutNVc4PQ>? MkDPNlMyPDh4OES=
HMEC M3SxeWNmdGxiVnnhZoltcXS7IFHzd4F6 M3z2TFUxOCCwTR?= NIWwWFM4OiCq NXjmRoJuTE2VTx?= NFjofpBz\XO3bITzJIlvKEdzL2OtdIhie2ViYXPjeY12dGG2aX;uJINwdWKrbnXkJJdqfGhiTVutNVc4PQ>? MYeyN|E1QDZ6NB?=
U2OS  M2TRSWZ2dmO2aX;uJGF{e2G7 MUCyJOK2VQ>? Mnj4NE0zPCCq M1zVTIlv\HWlZYOgdIhwe3Cqb4L5cIF1cW:wIH;mJGNpczFiYYSgd4VzcW6nIEO0OUBifCCkb4ToJINwdmOnboTyZZRqd26|IHHzJIViemy7IHHzJFIhcCCjZoTldkBi\G2rbnnzeJJifGmxbh?= M4Oy[|IzQTN5MUS3
U2OS  MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NF3mZ4oxNTFyINM1US=> Mn;qNlQwPDhiaB?= NFXVfXJqdmirYnn0d{Bk\WyuIHfyc5d1cCCmb4PlJIRmeGWwZHXueIx6 NVKyfpdOOjJ7M{exOFc>
U937 NEnoOG9HfW6ldHnvckBCe3OjeR?= NXG1V4R3OTByLUWwNEBvVQ>? MnnDOEBpyqB? NFXUUlNl\WO{ZXHz[ZMhfGinIHP5eIFz[WKrbnWtbY5lfWOnZDDDbIsyKGG3dH;wbI9{eGixconsZZRqd25iYYSgV4VzOjl4wrDhcoQheHKndnXueJMhS2SlMkXBJIRwf26{ZXf1cIF1cW:w NWfQdngxOjJ6Nkm4Olk>
U937 NXrreWtGTnWwY4Tpc44hSXO|YYm= MoLiNVAxKG6P M3T2R|QhcMLi Ml7HdoV3\XK|ZYOgeIhmKGO7dHHyZYJqdmVvaX7keYNm\CCrbnjpZol1cW:wIH;mxsA{UC22aIntbYRqdmViaX7jc5Jxd3KjdHnvckBqdnSxIFTORS=> NHjCUlczOjh4OUi2PS=>
U937 MkHJSpVv[3Srb36gRZN{[Xl? NHHJXWkyODBvNUCwJI5O MXe0JIjDqA>? MoG1bY5lfWOnczDpcoNz\WG|ZXSgdIhwe3Cqb4L5cIF1cW:wIH;mJGgzSVh? NYTrTJY2OjJ6Nkm4Olk>
HL-60 NGCx[4hCeG:ydH;zbZMhSXO|YYm= MVezNE8yODBxM{CwJI5O MoLrNlQhcA>? M2HjVmROW09? NEXWcmZmdmijbnPld{BkgXSjcnHibY5mNWmwZIXj[YQh[XCxcITvd4l{ NFy2RmczOjh4OUi2PS=>
ML-1 NXuybpB1SXCxcITvd4l{KEG|c3H5 MnLuNlUwPTBxMUCwJI5O NHXxU2IzPCCq MlnRSG1UVw>? M17lWIVvcGGwY3XzJIN6fGG{YXLpcoUucW6mdXPl[EBieG:ydH;zbZM> NHvn[48zOjh4OUi2PS=>
HCT116 NYP3NlR4TnWwY4Tpc44hSXO|YYm= MYCxJOK2VQ>? NXTNWVFNOjRiaB?= MluyZYJzd2ejdHXzJI9nKGOnbHygZ5lkdGViYYLy[ZN1yqB? M2nGSVIzPTFyNU[w
U2OS NUXCR|R{TnWwY4Tpc44hSXO|YYm= M2XXSVEhyrWP NGjBVVAzPCCq MV\hZpJw\2G2ZYOgc4Yh[2WubDDjfYNt\SCjcoLld5TDqA>? NX;je|RoOjJ3MUC1OlA>

... 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)

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* 必須

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID