MK-8776 (SCH 900776)

For research use only.

Catalog No.S2735

45 publications

MK-8776 (SCH 900776) Chemical Structure

CAS No. 891494-63-6

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.

Selleck's MK-8776 (SCH 900776) has been cited by 45 publications

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
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HCT115 M1\aO2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnXLNlAxNzJyMECgcm0> NWrtZ5VIOjRiaB?= MV\k[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? Ml63QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR|NUm1NlYoRjJ2M{W5OVI3RC:jPh?=
SW620 M1ywfGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYfwR2tsOjByL{KwNFAhdk1? NFPX[48zPCCq MYfk[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? M1\zWVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2M{W5OVI3Lz5{NEO1PVUzPjxxYU6=
IGROV-1 NHy4d3FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYDSc5htOjByL{KwNFAhdk1? MoTKNlQhcA>? M1L6TYRm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= NInEPVI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEO1PVUzPid-MkSzOVk2OjZ:L3G+
HCT116 M3nOcWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXixb|ZxOjByL{KwNFAhdk1? NYi1XZJoOjRiaB?= NELSXW1l\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= MVe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDN3OUWyOkc,OjR|NUm1NlY9N2F-
MCF10A M2K5PWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M33rS|IxOC9{MECwJI5O MoH0NlQhcA>? MlXi[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n NHLuUGU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEO1PVUzPid-MkSzOVk2OjZ:L3G+
MiaPaCa-2 MkPBS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmHaNlAxNzJyMECgcm0> MoDINlQhcA>? Mmjz[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n NEDRcZU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEO1PVUzPid-MkSzOVk2OjZ:L3G+
MDA-MB-231 M1\nVmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWHveoNpOjByL{KwNFAhdk1? NFPacYEzPCCq NIDnZXBl\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= MkGzQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR|NUm1NlYoRjJ2M{W5OVI3RC:jPh?=
HCC2998 NXuwfld7T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1L4bVIxOC9{MECwJI5O NF;5dIYzPCCq NVfpSXJJ\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l M1z3XlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2M{W5OVI3Lz5{NEO1PVUzPjxxYU6=
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U937 NEK0ZWVHfW6ldHnvckBCe3OjeR?= NFnXRo0yODBvNUCwJI5O M3GyPFQhcMLi NUfGfFI5cW6mdXPld{BqdmO{ZXHz[YQheGixc4Doc5J6dGG2aX;uJI9nKEh{QWi= NUDuNpV5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkK4Olk5PjlpPkKyPFY6QDZ7PD;hQi=>
HL-60 MXrBdI9xfG:|aYOgRZN{[Xl? M1;PNlMxNzFyMD:zNFAhdk1? NGHvfmMzPCCq NXXwcGJTTE2VTx?= MmS1[Y5p[W6lZYOgZ5l1[XKjYnnu[U1qdmS3Y3XkJIFxd3C2b4Ppdy=> NUHGNm1PRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkK4Olk5PjlpPkKyPFY6QDZ7PD;hQi=>
ML-1 MoPnRZBweHSxc3nzJGF{e2G7 NUPvdJhHOjVxNUCvNVAxKG6P MVuyOEBp NX;L[VZMTE2VTx?= M1vzeYVvcGGwY3XzJIN6fGG{YXLpcoUucW6mdXPl[EBieG:ydH;zbZM> NF\2[4g9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{Mki2PVg3QSd-MkK4Olk5Pjl:L3G+
HCT116 MVPGeY5kfGmxbjDBd5NigQ>? NV\kWldIOSEEtV2= M4rITlI1KGh? MlTKZYJzd2ejdHXzJI9nKGOnbHygZ5lkdGViYYLy[ZN1yqB? NFnSN2o9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkWxNFU3OCd-MkK1NVA2PjB:L3G+
U2OS NW\hemh5TnWwY4Tpc44hSXO|YYm= NYr0fWVkOSEEtV2= M1u4S|I1KGh? MUnhZpJw\2G2ZYOgc4Yh[2WubDDjfYNt\SCjcoLld5TDqA>? MkLuQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ3MUC1OlAoRjJ{NUGwOVYxRC:jPh?=
Sf9 NVfubJV[TnWwY4Tpc44h[XO|YYm= MXvJcohq[mm2aX;uJI9nKHKnY3;tZolv[W62IFPET|IwS3mlbHnuJGEh\XiycnXzd4VlKGmwIHnud4VkfCCVZkmgZ4VtdHNiYYPz[ZN{\WRiYYOgbY5pcWKrdHnvckBw\iCdM{PQYU1CXFBiaX7jc5Jxd3KjdHnvckBqdnSxIHLpc5RqdnmuYYTl[EBpcXO2b37lJGgyKGGodHXyJFEhcHJiYomgcIlyfWmmIIPjbY51cWyuYYTpc44h[2:3boTpcoctKEmFNUCgQUAxNjF4IN88UU4> NV3kSYdURGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkGwPVQ3ODdpPkKxNFk1PjB5PD;hQi=>

... 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]
- Collapse
  • Animal Models: Female nude mice injected subcutaneously with A2780 or MiaPaCa2 cells
  • 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
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)
Dosage mg/kg Average weight of animals g Dosing volume per animal ul Number of animals
Step 2: Enter the in vivo formulation ()
% DMSO % % Tween 80 % ddH2O
CalculateReset

Bio Calculators

Molarity Calculator

Molarity Calculator

Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

Mass (mg) = Concentration (mM) × Volume (mL) × Molecular Weight (g/mol)

  • Mass
    Concentration
    Volume
    Molecular Weight

*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and SDS / COA (available on product pages).

Dilution Calculator

Dilution Calculator

Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

Concentration (start) x Volume (start) = Concentration (final) x Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

  • C1
    V1
    C2
    V2

* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and SDS / COA (available online).

The Serial Dilution Calculator Equation

  • Serial Dilutions

  • Computed Result

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):
Molecular Weight Calculator

Molecular Weight Calculator

Enter the chemical formula of a compound to calculate its molar mass and elemental composition:

Total Molecular Weight: g/mol

Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

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 Corp. October 17 2008 Phase 1

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

If you have any other enquiries, please leave a message.

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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.

Chk Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID