MK-8776 (SCH 900776)

Catalog No.S2735

MK-8776 (SCH 900776) Chemical Structure

Molecular Weight(MW): 376.25

MK-8776 (SCH 900776) is a selective Chk1 inhibitor with IC50 of 3 nM in a cell-free assay. It shows 500-fold selectivity against Chk2. Phase 2.

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Cited by 17 Publications

6 Customer Reviews

  • Hela cell was trypsinized and plated at 30% confluence in DMEM. 16 hours later, MK-8776 (SCH900776) was added at final concentrations of 0, 5, 10 and 25uM. Another 24 hours later, cells were harvested in RIPA with protease and phosphatase inhibitor cocktail. Total protein concentration was measured by BCA method. Lysates equivalent to 20ug total protein were subject to Western Blot, using total- CHK1, pS345-CHK1 and beta-actin (internal control) antibodies.

    MK-8776 (SCH 900776) purchased from Selleck.

  • Western blots of proteins associated with Chk1 activation and apoptosis.

    Biomaterials, 2018, 182:35-43. MK-8776 (SCH 900776) purchased from Selleck.

  • MCF7 cells were seeded in 60 mm dishes and were pretreated with the specified inhibitor 1 h before stimulation with either vehicle or doxorubicin. Twenty-four hours after treatment, cells were collected and immunoblotted for nSMase2 and actin.

    Cell Death Dis, 2015, 6:e1947.. MK-8776 (SCH 900776) purchased from Selleck.

  • SK-MES-1 cells were treated with 5 nM gemcitabine for 4 hours. The drug was then replaced with MK-8776 at the indicated doses and the cells harvested after an additional 6 hours. Cell lysates were analyzed by Western blotting for the indicated protein.

    Sci Rep, 2017, 7(1):15031. MK-8776 (SCH 900776) purchased from Selleck.

  • (A, B) In the three TNBC cell lines, the numbers of autophagy-related spots were significantly increased in IR-alone group, and this effect was significantly suppressed by MK-8776 (IR vs MK-8776+IR: 65±23 vs 13±8, P<0.0001 in MDA-MB-231; 57±32 vs 18±7, P=0.0014 in BT-549; 43±35 vs 14±10, P=0.021 in CAL-51).

    Acta Pharmacol Sin, 2017, 38(4):513-523. MK-8776 (SCH 900776) purchased from Selleck.

  • HT29 cells were treated with 1 μM V411, 3 μM LY2603618 (LY), 3 μM MK-8776 (MK), 3 μM GNE-900 (GNE) or 0.3 μM ARRY-1A (ARRY) for 24 h. The fraction of γH2AX, pRPA32 (S4/S8), pChk1 (S317) or pChk2 (T68) positive nuclei were determined by single cell immunofluorescent imaging (n=4, mean ± SD). B. HT29 cells were treated as above for 2 or 24 h. Cell lysates were probed with the indicated antibodies by immunoblotting.

    Oncotarget, 2016, 7(51):85033-85048. MK-8776 (SCH 900776) purchased from Selleck.

Purity & Quality Control

Choose Selective Chk Inhibitors

Biological Activity

Description MK-8776 (SCH 900776) is a selective Chk1 inhibitor with IC50 of 3 nM in a cell-free assay. It shows 500-fold selectivity against Chk2. Phase 2.
Targets
Chk1 [1]
(Cell-free assay)
CDK2 [1]
(Cell-free assay)
3 nM 0.16 μM
In vitro

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 Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
U251 MoXvS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXHQcYk2OjByL{KwNFAhdk1? NWDLUFV6OjRiaB?= MkTN[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n MXqyOFM2QTV{Nh?=
HCT115 MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX3lXFk2OjByL{KwNFAhdk1? MV[yOEBp MX;k[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? Mn7rNlQ{PTl3Mk[=
SW620 NFmye5JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1X1ZVIxOC9{MECwJI5O MYKyOEBp MnjN[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n Mn6wNlQ{PTl3Mk[=
IGROV-1 NX\RPZZQT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYjtSVJ5OjByL{KwNFAhdk1? NELXfHUzPCCq M2m1boRm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= MV6yOFM2QTV{Nh?=
HCT116 M3HYdmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWfkRm1JOjByL{KwNFAhdk1? NVX4fVRxOjRiaB?= NXLNb4RH\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l M3;TOlI1OzV7NUK2
MCF10A NEDtfY5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2iwV|IxOC9{MECwJI5O Mo\2NlQhcA>? MUnk[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? NHn1emwzPDN3OUWyOi=>
MiaPaCa-2 MmrZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1jsRlIxOC9{MECwJI5O MYOyOEBp MonO[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n MkjtNlQ{PTl3Mk[=
MDA-MB-231 M17zdmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVuyNFAwOjByMDDuUS=> NYXuPYc{OjRiaB?= NXHqNmx3\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l NXm4fWx4OjR|NUm1NlY>
HCC2998 MkCyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFXsZnozODBxMkCwNEBvVQ>? NFOweI4zPCCq MWHk[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? NV7ZOJAyOjR|NUm1NlY>
U87 NFm5XZNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVX4RnBNOjByL{KwNFAhdk1? NFr6VXUzPCCq M17Dc4Rm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= M3TjOlI1OzV7NUK2
MDA-MB-435 MYrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mn;CNlAxNzJyMECgcm0> M3nZdVI1KGh? MUXk[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? Mkn4NlQ{PTl3Mk[=
SNB19 NI[we2FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NU\peXRMOjByL{KwNFAhdk1? NEHPdYozPCCq NYH0XpRR\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l M2C5blI1OzV7NUK2
U20S MoewS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoLvNlAxNzJyMECgcm0> NUTUVW1tOjRiaB?= Mo[1[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n MV2yOFM2QTV{Nh?=
A498 NEHOWYpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXv0coFZOjByL{KwNFAhdk1? Mn7LNlQhcA>? NI\Id5Fl\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= NY\ESpBOOjR|NUm1NlY>
TK10 M1fBWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3O0clIxOC9{MECwJI5O MkPhNlQhcA>? NYnNWoRj\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l MoPmNlQ{PTl3Mk[=
AsPC-1 NITKfIxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{G5UlIxOC9{MECwJI5O NFzS[o8zPCCq NH\LS3Bl\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= M361UlI1OzV7NUK2
H23 NGO3XYdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4XJc|UxOCCwTR?= NGi1cGUzPCCq NFHEUZpFVVOR MmXV[Y5p[W6lZYOgeIhmKGOqZX3vd4Vve2m2aYrheIlwdiC2bzDQUXg> Mn7oNlQyOTN3NEm=
H1437 NWPaZoE6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnnlOVAxKG6P NYnCdoU6OjRiaB?= MVfEUXNQ MnjX[Y5p[W6lZYOgeIhmKGOqZX3vd4Vve2m2aYrheIlwdiC2bzDQUXg> Mk[0NlQyOTN3NEm=
H1993 M2Pxb2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2qzNlUxOCCwTR?= M1nYOlI1KGh? NXSycFg2TE2VTx?= M3LXc4VvcGGwY3XzJJRp\SClaHXtc5NmdnOrdHn6ZZRqd25idH:gVG1Z NWXkZ2VTOjRzMUO1OFk>
H1299 M160TGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVnVNWZXPTByIH7N Mo[yNlQhcA>? MmPZSG1UVw>? MYTlcohidmOnczD0bIUh[2inbX;z[Y5{cXSrenH0bY9vKHSxIGDNXC=> M4XYcVI1OTF|NUS5
AsPC-1 MoXyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUOxNE0yODByIH7N MXSyOE01QGh? NF;rNWxmdmijbnPld{B1cGViY3jlcY9{\W6|aYTpfoF1cW:wIITvJIdmdWOrdHHibY5m NV\rTFlyOjN6MES0NlI>
MiaPaCa-2 MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIfHdVMyOC1zMECwJI5O MkDNNlQuPDiq NVHidFIy\W6qYX7j[ZMhfGinIHPo[Y1we2Wwc3n0bZpifGmxbjD0c{Bo\W2laYThZolv\Q>? MWqyN|gxPDR{Mh?=
BxPC-3 M4L0dWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFHEZ4EyOC1zMECwJI5O NIW2XXUzPC12OHi= Mnrh[Y5p[W6lZYOgeIhmKGOqZX3vd4Vve2m2aYrheIlwdiC2bzDn[Y1kcXSjYnnu[S=> MonBNlM5ODR2MkK=
SKOV3 NHHybGVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoHCNE4{KML3TR?= MkXiPEBl NVjBR3c4e2Wwc3n0bZpmeyC2aHWgZ4VtdCCuaX7ld{B1dyCpZX3jbZRi[mmwZdMg NGTqOJkzOzV2OEK2PS=>
OVCAR-8 MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUHxV|lvOC5|INM1US=> M4DXXlgh\A>? NFu5SWF{\W6|aYTpfoV{KHSqZTDj[YxtKGyrbnXzJJRwKGenbXPpeIFjcW6nwrC= NYjwOZhHOjN3NEiyOlk>
MV-4-11 M13ZZWFxd3C2b4Ppd{BCe3OjeR?= M1rsbFExOC15MECgcm0> NGrDb2c1QCCq M{HoPYlv\HWlZYOgZZBweHSxc3nzJIRwe2ViZHXw[Y5l\W62bIm= NV6xd4JnOjN3M{[3NlE>
U937 NXX0dIpDSXCxcITvd4l{KEG|c3H5 MmTzNVAxNTdyMDDuUS=> M{nWZ|Q5KGh? NYD1UJppcW6mdXPld{BieG:ydH;zbZMh\G:|ZTDk[ZBmdmSnboTsfS=> Ml7kNlM2OzZ5MkG=
MOLM-13  NU\sXYFYSXCxcITvd4l{KEG|c3H5 NUe0WVJSOTByLUewNEBvVQ>? MoTmOFghcA>? NXHiRmJucW6mdXPld{BieG:ydH;zbZMh\G:|ZTDk[ZBmdmSnboTsfS=> MV6yN|U{Pjd{MR?=
A2058  NFjHOlNE\WyuIG\pZYJqdGm2eTDBd5NigQ>? MkX6N|cvPS1|MECgcm0> MnzuO|IhcA>? NYDoflNZTE2VTx?= NU\HSFR5emWmdXPld{B1cGViTVutNVc4PSCHQ{WwxsBjgSB3LX\vcIQhfG9iYX6gZZZmemGpZTDv[kA1PSCwTR?= M3PMR|I{OTR6Nki0
H2009 NXP4[pBVS2WubDDWbYFjcWyrdImgRZN{[Xl? Mkn5OVAxKG6P NWrXeYhuPzJiaB?= MYDEUXNQ MkjrdoV{fWy2czDpckBIOS:VLYDoZZNmKGGlY4XteYxifGmxbjDjc41jcW6nZDD3bZRpKE2NLUG3O|U> NILoOIozOzF2OE[4OC=>
Su.86.86 MVnD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NWTENlUzPTByIH7N MoDvO|IhcA>? MYDEUXNQ MVny[ZN2dHS|IHnuJGcyN1NvcHjhd4Uh[WOldX31cIF1cW:wIHPvcYJqdmWmIIfpeIghVUtvMUe3OS=> Mo\pNlMyPDh4OES=
HRE Ml7BR4VtdCCYaXHibYxqfHliQYPzZZk> MXq1NFAhdk1? M330eFczKGh? NXzTcnpzTE2VTx?= M1PUbZJme3WudIOgbY4hTzFxUz3wbIF{\SCjY3P1cZVt[XSrb36gZ49u[mmwZXSge4l1cCCPSz2xO|c2 NHK4O|QzOzF2OE[4OC=>
HMEC NXj6SoVRS2WubDDWbYFjcWyrdImgRZN{[Xl? M{HYZlUxOCCwTR?= NEGzVHQ4OiCq M2r5bGROW09? NH\tUo9z\XO3bITzJIlvKEdzL2OtdIhie2ViYXPjeY12dGG2aX;uJINwdWKrbnXkJJdqfGhiTVutNVc4PQ>? MWeyN|E1QDZ6NB?=
U2OS  MmD2SpVv[3Srb36gRZN{[Xl? NHX0bZEzKML3TR?= NXr0WpBSOC1{NDDo MVPpcoR2[2W|IIDoc5NxcG:{eXzheIlwdiCxZjDDbIsyKGG2IIPldolv\SB|NEWgZZQh[m:2aDDjc45k\W62cnH0bY9veyCjczDlZZJtgSCjczCyJIgh[W[2ZYKgZYRucW6rc4TyZZRqd25? MlLPNlI6OzdzNEe=
U2OS  M1nBe2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2jufFAuOTBiwsXN M1nhUVI1NzR6IHi= Mn7LbY5pcWKrdIOgZ4VtdCCpcn;3eIgh\G:|ZTDk[ZBmdmSnboTsfS=> MX[yNlk{PzF2Nx?=
U937 MkPjSpVv[3Srb36gRZN{[Xl? NEHucHAyODBvNUCwJI5O MVO0JIjDqA>? NVjPV4xm\GWlcnXhd4V{KHSqZTDjfZRiemGkaX7lMYlv\HWlZXSgR4hsOSCjdYTvdIhwe3Cqb4L5cIF1cW:wIHH0JHNmejJ7NtMgZY5lKHC{ZY\lcpR{KEOmY{K1RUBld3ewcnXneYxifGmxbh?= NETN[2czOjh4OUi2PS=>
U937 MVrGeY5kfGmxbjDBd5NigQ>? NGHSOmQyODBibl2= MVy0JIjDqA>? NV\DZ2pxemW4ZYLz[ZMhfGinIHP5eIFz[WKrbnWtbY5lfWOnZDDpcohq[mm2aX;uJI9nyqB|SD30bJlucWSrbnWgbY5kd3Kyb4LheIlwdiCrboTvJGRPSQ>? MoiwNlI5Pjl6Nkm=
U937 MnHoSpVv[3Srb36gRZN{[Xl? M{DYc|ExOC13MECgcm0> M1rCNFQhcMLi M1i1R4lv\HWlZYOgbY5kemWjc3XkJJBpd3OyaH;yfYxifGmxbjDv[kBJOkG[ NHexVXkzOjh4OUi2PS=>
HL-60 NHHMTGZCeG:ydH;zbZMhSXO|YYm= M2HjOVMxNzFyMD:zNFAhdk1? NETIUFczPCCq Ml7ZSG1UVw>? NHLEcVlmdmijbnPld{BkgXSjcnHibY5mNWmwZIXj[YQh[XCxcITvd4l{ M3H4eVIzQDZ7OE[5
ML-1 NWPIWYRwSXCxcITvd4l{KEG|c3H5 M4jZb|I2NzVyL{GwNEBvVQ>? MX6yOEBp MlHhSG1UVw>? MYHlcohidmOnczDjfZRiemGkaX7lMYlv\HWlZXSgZZBweHSxc3nz MnPYNlI5Pjl6Nkm=
HCT116 MYPGeY5kfGmxbjDBd5NigQ>? NFT0e|EyKML3TR?= NXiyOXJlOjRiaB?= NFPvenRi[nKxZ3H0[ZMhd2ZiY3XscEBkgWOuZTDhdpJme3UEoB?= MUmyNlUyODV4MB?=
U2OS MXnGeY5kfGmxbjDBd5NigQ>? MkTONUDDvU1? NXPmVWJGOjRiaB?= NETnTJRi[nKxZ3H0[ZMhd2ZiY3XscEBkgWOuZTDhdpJme3UEoB?= NILtVo8zOjVzMEW2NC=>

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
p-chk1(ser345) / CDC25A ; 

PubMed: 27690219     


Western blots for H1299 and A549 cells treated with MK-8776 for various times and assessed for expression of p-chk1 (ser345) and CDC25A.

Cyclin E / pY15-CDK / γH2AX ; 

PubMed: 26595527     


The indicated cell lines were incubated with 2 μM of each drug for 6 h, then lysed and analyzed by western blotting. The top row reflects cells sensitive to MK-8776. The second row reflects cells that are also sensitive to MK-8776, but which fail to degrade cyclin E. The third row reflects MK-8776-resistant cell lines.

27690219 26595527
In vivo 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]

Protocol

Animal Research:[1]
+ Expand
  • Animal Models: Female nude mice injected subcutaneously with A2780 or MiaPaCa2 cells
  • Formulation: Formulated in 20% hydroxypropyl β-cyclodextrin
  • Dosages: ~50 mg/kg
  • Administration: Administered intraperitoneally
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 3 mg/mL (7.97 mM)
Water Insoluble
Ethanol Insoluble
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
4% DMSO+30% propylene glycol
For best results, use promptly after mixing.
5 mg/mL

* 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.

Chemical Information

Molecular Weight 376.25
Formula

C15H18BrN7

CAS No. 891494-63-6
Storage powder
in solvent
Synonyms N/A

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

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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.

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID