MK-8776 (SCH 900776)

Catalog No.S2735

For research use only.

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.

MK-8776 (SCH 900776) Chemical Structure

CAS No. 891494-63-6

Selleck's MK-8776 (SCH 900776) has been cited by 55 publications

Purity & Quality Control

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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 MofmS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGHKZ3IzODBxMkCwNEBvVQ>? MnHDNlQhcA>? MYLk[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? MoPBQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR|NUm1NlYoRjJ2M{W5OVI3RC:jPh?=
HCT115 NGHhdI9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmH2NlAxNzJyMECgcm0> M2rlVFI1KGh? MlK1[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n MYm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDN3OUWyOkc,OjR|NUm1NlY9N2F-
SW620 Mn20S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWjp[GlMOjByL{KwNFAhdk1? M4nt[VI1KGh? NEXaWYNl\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= NGH2W3g9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEO1PVUzPid-MkSzOVk2OjZ:L3G+
IGROV-1 NXG2O3lNT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGq0T|IzODBxMkCwNEBvVQ>? MXuyOEBp MlXy[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n NFP3TJg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEO1PVUzPid-MkSzOVk2OjZ:L3G+
HCT116 M1i1WWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXvjVZFZOjByL{KwNFAhdk1? NX3QVoV1OjRiaB?= NX\WdIp2\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l MnXOQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR|NUm1NlYoRjJ2M{W5OVI3RC:jPh?=
MCF10A NFHX[mFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWjDPWl4OjByL{KwNFAhdk1? MofsNlQhcA>? NHy2VJFl\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= NYrHO|l7RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSzOVk2OjZpPkK0N|U6PTJ4PD;hQi=>
MiaPaCa-2 MXfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYOyNFAwOjByMDDuUS=> NHTQXXMzPCCq Mlez[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n NUC4OVZ7RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSzOVk2OjZpPkK0N|U6PTJ4PD;hQi=>
MDA-MB-231 NIntVYRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGOyW3czODBxMkCwNEBvVQ>? NVTxbVVsOjRiaB?= MX;k[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? M2CwV|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2M{W5OVI3Lz5{NEO1PVUzPjxxYU6=
HCC2998 MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHi4eZkzODBxMkCwNEBvVQ>? Moj4NlQhcA>? NH[2bpdl\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= MXG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDN3OUWyOkc,OjR|NUm1NlY9N2F-
U87 M1ezfmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUXXZZg5OjByL{KwNFAhdk1? MUGyOEBp MXnk[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? NYTQNpZsRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSzOVk2OjZpPkK0N|U6PTJ4PD;hQi=>
MDA-MB-435 MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3fJ[lIxOC9{MECwJI5O MXGyOEBp Mons[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n MVK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDN3OUWyOkc,OjR|NUm1NlY9N2F-
SNB19 MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MX[yNFAwOjByMDDuUS=> MWiyOEBp MlXG[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n NFvvV449[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEO1PVUzPid-MkSzOVk2OjZ:L3G+
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TK10 NXPI[FFRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2DiOVIxOC9{MECwJI5O M4njbVI1KGh? MWTk[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? M4HEXlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2M{W5OVI3Lz5{NEO1PVUzPjxxYU6=
AsPC-1 NIDhS4lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXSyNFAwOjByMDDuUS=> M4fWOlI1KGh? M3jiOoRm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= MkPJQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR|NUm1NlYoRjJ2M{W5OVI3RC:jPh?=
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H1299 MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEnSOlQ2ODBibl2= NFzqfIszPCCq M{Ppb2ROW09? NF3YT3dmdmijbnPld{B1cGViY3jlcY9{\W6|aYTpfoF1cW:wIITvJHBOYA>? NHXURok9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEGxN|U1QSd-MkSxNVM2PDl:L3G+
AsPC-1 MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NETpepMyOC1zMECwJI5O NX3vU3A2OjRvNEjo NXLK[|E1\W6qYX7j[ZMhfGinIHPo[Y1we2Wwc3n0bZpifGmxbjD0c{Bo\W2laYThZolv\Q>? NYPxNpd7RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO4NFQ1OjJpPkKzPFA1PDJ{PD;hQi=>
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U937 NU\Bc5hyTnWwY4Tpc44hSXO|YYm= MXixNFAuPTByIH7N M{nqWlQhcMLi NF;ye|RqdmS3Y3XzJIlv[3KnYYPl[EBxcG:|cHjvdplt[XSrb36gc4YhUDKDWB?= MY[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjh4OUi2PUc,OjJ6Nkm4Olk9N2F-
HL-60 MmmyRZBweHSxc3nzJGF{e2G7 NV3TWY5zOzBxMUCwM|MxOCCwTR?= NWHWeVY6OjRiaB?= MV\EUXNQ NYjac4FL\W6qYX7j[ZMh[3m2YYLhZolv\S2rbnT1Z4VlKGGyb4D0c5Nqew>? MYO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjh4OUi2PUc,OjJ6Nkm4Olk9N2F-
ML-1 M{DZRWFxd3C2b4Ppd{BCe3OjeR?= MkG4NlUwPTBxMUCwJI5O MUOyOEBp NX3zbHNKTE2VTx?= M4POcoVvcGGwY3XzJIN6fGG{YXLpcoUucW6mdXPl[EBieG:ydH;zbZM> M1L1PFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{OE[5PFY6Lz5{Mki2PVg3QTxxYU6=
HCT116 M1nGU2Z2dmO2aX;uJGF{e2G7 NELFWGUyKML3TR?= MXmyOEBp NHroPFNi[nKxZ3H0[ZMhd2ZiY3XscEBkgWOuZTDhdpJme3UEoB?= NIjEXGw9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkWxNFU3OCd-MkK1NVA2PjB:L3G+
U2OS MljrSpVv[3Srb36gRZN{[Xl? MXOxJOK2VQ>? MoGzNlQhcA>? MULhZpJw\2G2ZYOgc4Yh[2WubDDjfYNt\SCjcoLld5TDqA>? MlK0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ3MUC1OlAoRjJ{NUGwOVYxRC:jPh?=
Sf9 MW\GeY5kfGmxbjDhd5NigQ>? MWTJcohq[mm2aX;uJI9nKHKnY3;tZolv[W62IFPET|IwS3mlbHnuJGEh\XiycnXzd4VlKGmwIHnud4VkfCCVZkmgZ4VtdHNiYYPz[ZN{\WRiYYOgbY5pcWKrdHnvckBw\iCdM{PQYU1CXFBiaX7jc5Jxd3KjdHnvckBqdnSxIHLpc5RqdnmuYYTl[EBpcXO2b37lJGgyKGGodHXyJFEhcHJiYomgcIlyfWmmIIPjbY51cWyuYYTpc44h[2:3boTpcoctKEmFNUCgQUAxNjF4IN88UU4> NHTyUlI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUC5OFYxPyd-MkGwPVQ3ODd:L3G+
Assay
Methods Test Index PMID
Western blot p-chk1(ser345) / CDC25A ; Cyclin E / pY15-CDK / γH2AX 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 (from reference)

Animal Research:[1]
  • Animal Models: Female nude mice injected subcutaneously with A2780 or MiaPaCa2 cells
  • Dosages: ~50 mg/kg
  • Administration: Administered intraperitoneally

Solubility (25°C)

In vitro

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

Chemical Information

Molecular Weight 376.25
Formula

C15H18BrN7

CAS No. 891494-63-6
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CN1C=C(C=N1)C2=C3N=C(C(=C(N3N=C2)N)Br)C4CCCNC4

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT00779584 Completed Drug: MK-8776|Drug: Gemcitabine Hodgkin Disease|Lymphoma Non-Hodgkin|Neoplasms Merck Sharp & Dohme LLC October 17 2008 Phase 1

(data from https://clinicaltrials.gov, updated on 2022-08-01)

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

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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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