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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4 Customer Reviews

  • 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.

    (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.

    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.

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 NWSwOoNkT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFnXeGMzODBxMkCwNEBvVQ>? MmLNNlQhcA>? Mnex[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n MmDyNlQ{PTl3Mk[=
HCT115 NFvQeJBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWqyNFAwOjByMDDuUS=> Mn7nNlQhcA>? M1mzfIRm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= M{\3VFI1OzV7NUK2
SW620 NXHNXnBRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NETGfHAzODBxMkCwNEBvVQ>? NWDYNlF{OjRiaB?= M1ezeIRm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= NXv6[JZROjR|NUm1NlY>
IGROV-1 MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXfkcFBTOjByL{KwNFAhdk1? MUWyOEBp NITEdWdl\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= NX;4cWVROjR|NUm1NlY>
HCT116 MkXFS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVeyNFAwOjByMDDuUS=> MoLONlQhcA>? NE\SfZNl\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= NWLxcGJnOjR|NUm1NlY>
MCF10A MYLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmniNlAxNzJyMECgcm0> Mnf1NlQhcA>? NW\VV|NX\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l NVrSVlNpOjR|NUm1NlY>
MiaPaCa-2 NEG3TlRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1HJXVIxOC9{MECwJI5O NUXMXG1yOjRiaB?= NF7UW3Fl\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= MlHsNlQ{PTl3Mk[=
MDA-MB-231 MlWzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NF31cYszODBxMkCwNEBvVQ>? NWTP[ZJ[OjRiaB?= MVnk[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? NVTUfXdqOjR|NUm1NlY>
HCC2998 M3rE[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXGyNFAwOjByMDDuUS=> MXWyOEBp NFvKUW5l\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= NHnPcmIzPDN3OUWyOi=>
U87 M1:x[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1XSd|IxOC9{MECwJI5O MWmyOEBp MlrQ[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n NITxUowzPDN3OUWyOi=>
MDA-MB-435 MXTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXyyNFAwOjByMDDuUS=> NHX2PIEzPCCq MX3k[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? MVWyOFM2QTV{Nh?=
SNB19 NXqwVIhLT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHPqb44zODBxMkCwNEBvVQ>? NX70UY9EOjRiaB?= MlzW[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n NV\RUFB1OjR|NUm1NlY>
U20S MlXoS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M375V|IxOC9{MECwJI5O Ml\3NlQhcA>? MmS3[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n Mle3NlQ{PTl3Mk[=
A498 MlW3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MX6yNFAwOjByMDDuUS=> M4DTd|I1KGh? MmjK[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n M3nj[lI1OzV7NUK2
TK10 MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIDQcpczODBxMkCwNEBvVQ>? M1voeFI1KGh? M4jEOYRm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= MmjQNlQ{PTl3Mk[=
AsPC-1 M2ThWmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M37JSlIxOC9{MECwJI5O NXjhSG06OjRiaB?= NEnPXZFl\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= NWfxWXBOOjR|NUm1NlY>
H23 MV3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4jUVVUxOCCwTR?= NUeyZmNHOjRiaB?= M2q3eWROW09? MVrlcohidmOnczD0bIUh[2inbX;z[Y5{cXSrenH0bY9vKHSxIGDNXC=> NGD0OGkzPDFzM{W0PS=>
H1437 NIrycIxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2LnT|UxOCCwTR?= M3\EflI1KGh? NX3oRnNtTE2VTx?= MmTT[Y5p[W6lZYOgeIhmKGOqZX3vd4Vve2m2aYrheIlwdiC2bzDQUXg> NXrWfmN4OjRzMUO1OFk>
H1993 M1O3UWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIXIWVg2ODBibl2= NH3aZZAzPCCq NYW2d5pXTE2VTx?= NH\2OYhmdmijbnPld{B1cGViY3jlcY9{\W6|aYTpfoF1cW:wIITvJHBOYA>? MmX5NlQyOTN3NEm=
H1299 NGfEO5VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIn4RpQ2ODBibl2= MoHYNlQhcA>? MV;EUXNQ NIryUJVmdmijbnPld{B1cGViY3jlcY9{\W6|aYTpfoF1cW:wIITvJHBOYA>? Mmr3NlQyOTN3NEm=
AsPC-1 MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYP6[|J6OTBvMUCwNEBvVQ>? NXvsbY5MOjRvNEjo M2XTNYVvcGGwY3XzJJRp\SClaHXtc5NmdnOrdHn6ZZRqd25idH:g[4Vu[2m2YXLpcoU> MUmyN|gxPDR{Mh?=
MiaPaCa-2 M3[0N2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MofQNVAuOTByMDDuUS=> Mlj3NlQuPDiq MYXlcohidmOnczD0bIUh[2inbX;z[Y5{cXSrenH0bY9vKHSxIHflcYNqfGGkaX7l NFvjU5QzOzhyNESyNi=>
BxPC-3 MVfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Ml;INVAuOTByMDDuUS=> MWSyOE01QGh? MUflcohidmOnczD0bIUh[2inbX;z[Y5{cXSrenH0bY9vKHSxIHflcYNqfGGkaX7l MoPCNlM5ODR2MkK=
SKOV3 MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFK2XHUxNjNiwsXN NH\KTFE5KGR? MVPz[Y5{cXSrenXzJJRp\SClZXzsJIxqdmW|IITvJIdmdWOrdHHibY5myqB? M1iwVlI{PTR6Mk[5
OVCAR-8 NVHZOmZiT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mm\DNE4{KML3TR?= NH72UIw5KGR? MoDMd4Vve2m2aYrld{B1cGViY3XscEBtcW6nczD0c{Bo\W2laYThZolv\cLi M3y2TVI{PTR6Mk[5
MV-4-11 NWDsU21ZSXCxcITvd4l{KEG|c3H5 Mo\pNVAxNTdyMDDuUS=> NH;Db2Y1QCCq M{C4PIlv\HWlZYOgZZBweHSxc3nzJIRwe2ViZHXw[Y5l\W62bIm= Mn;tNlM2OzZ5MkG=
U937 NX\OVmVbSXCxcITvd4l{KEG|c3H5 M1\vdlExOC15MECgcm0> MWC0PEBp NXG5UHdFcW6mdXPld{BieG:ydH;zbZMh\G:|ZTDk[ZBmdmSnboTsfS=> NI\SVGUzOzV|NkeyNS=>
MOLM-13  NULBeFVnSXCxcITvd4l{KEG|c3H5 MmXJNVAxNTdyMDDuUS=> M2jj[VQ5KGh? NIn0TWpqdmS3Y3XzJIFxd3C2b4Ppd{Bld3OnIHTldIVv\GWwdHz5 MV:yN|U{Pjd{MR?=
A2058  MWLD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NHX0emE{Py53LUOwNEBvVQ>? MX63NkBp M4LpXWROW09? MnLLdoVlfWOnczD0bIUhVUtvMUe3OUBGSzVywrDifUA2NW[xbHSgeI8h[W5iYY\ldoFo\SCxZjC0OUBvVQ>? MXKyN|E1QDZ6NB?=
H2009 NVzmS2JpS2WubDDWbYFjcWyrdImgRZN{[Xl? Mn75OVAxKG6P MYC3NkBp NID0V|dFVVOR MXjy[ZN2dHS|IHnuJGcyN1NvcHjhd4Uh[WOldX31cIF1cW:wIHPvcYJqdmWmIIfpeIghVUtvMUe3OS=> MlqwNlMyPDh4OES=
Su.86.86 NEfiTVNE\WyuIG\pZYJqdGm2eTDBd5NigQ>? M1:3elUxOCCwTR?= NV:4b|k5PzJiaB?= NI\sT4tFVVOR MljldoV{fWy2czDpckBIOS:VLYDoZZNmKGGlY4XteYxifGmxbjDjc41jcW6nZDD3bZRpKE2NLUG3O|U> NUfuTJY5OjNzNEi2PFQ>
HRE NGXhOVBE\WyuIG\pZYJqdGm2eTDBd5NigQ>? Ml\nOVAxKG6P NIK5N5U4OiCq NUnQTIRJTE2VTx?= M3;lTJJme3WudIOgbY4hTzFxUz3wbIF{\SCjY3P1cZVt[XSrb36gZ49u[mmwZXSge4l1cCCPSz2xO|c2 NIr5[YMzOzF2OE[4OC=>
HMEC Mmi3R4VtdCCYaXHibYxqfHliQYPzZZk> NIjaRWM2ODBibl2= MnvuO|IhcA>? M1TMPWROW09? NEDJWJpz\XO3bITzJIlvKEdzL2OtdIhie2ViYXPjeY12dGG2aX;uJINwdWKrbnXkJJdqfGhiTVutNVc4PQ>? M3X6V|I{OTR6Nki0
U2OS  Mne4SpVv[3Srb36gRZN{[Xl? MkfpNkDDvU1? NHr2TWoxNTJ2IHi= NGnGUFVqdmS3Y3XzJJBpd3OyaH;yfYxifGmxbjDv[kBEcGtzIHH0JJNmemmwZTCzOFUh[XRiYn;0bEBkd26lZX70doF1cW:wczDhd{Bm[XKueTDhd{AzKGhiYX\0[ZIh[WSvaX7pd5Rz[XSrb36= Mo\QNlI6OzdzNEe=
U2OS  M4HxeGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MV2wMVExKML3TR?= MXyyOE81QCCq NED3Om9qdmirYnn0d{Bk\WyuIHfyc5d1cCCmb4PlJIRmeGWwZHXueIx6 NGLEOIozOjl|N{G0Oy=>
U937 NUXhb|k3TnWwY4Tpc44hSXO|YYm= NXizXYg1OTByLUWwNEBvVQ>? NYrTepFUPCCqwrC= NFTZZ2tl\WO{ZXHz[ZMhfGinIHP5eIFz[WKrbnWtbY5lfWOnZDDDbIsyKGG3dH;wbI9{eGixconsZZRqd25iYYSgV4VzOjl4wrDhcoQheHKndnXueJMhS2SlMkXBJIRwf26{ZXf1cIF1cW:w NV35[5dSOjJ6Nkm4Olk>
U937 M1XvOGZ2dmO2aX;uJGF{e2G7 MU[xNFAhdk1? Ml7DOEBpyqB? M4TreJJmfmW{c3XzJJRp\SCleYThdoFjcW6nLXnu[JVk\WRiaX7obYJqfGmxbjDv[uKhO0hvdHj5cYllcW6nIHnuZ49zeG:{YYTpc44hcW62bzDEUmE> MVOyNlg3QTh4OR?=
U937 NHvPZXhHfW6ldHnvckBCe3OjeR?= NEjUW4UyODBvNUCwJI5O MoHtOEBpyqB? M4\tTIlv\HWlZYOgbY5kemWjc3XkJJBpd3OyaH;yfYxifGmxbjDv[kBJOkG[ NGnyS3YzOjh4OUi2PS=>
HL-60 NYX1PYNKSXCxcITvd4l{KEG|c3H5 NF;iXGM{OC9zMECvN|AxKG6P M4P2R|I1KGh? M2\WV2ROW09? M33EXoVvcGGwY3XzJIN6fGG{YXLpcoUucW6mdXPl[EBieG:ydH;zbZM> MV[yNlg3QTh4OR?=
ML-1 NEXkdnFCeG:ydH;zbZMhSXO|YYm= NELEOVkzPS93MD:xNFAhdk1? MYiyOEBp NIrpd3JFVVOR M3;STYVvcGGwY3XzJIN6fGG{YXLpcoUucW6mdXPl[EBieG:ydH;zbZM> NW\BfpNUOjJ6Nkm4Olk>
HCT116 NIXwUWhHfW6ldHnvckBCe3OjeR?= MlfJNUDDvU1? M{Dx[lI1KGh? NH[1cpVi[nKxZ3H0[ZMhd2ZiY3XscEBkgWOuZTDhdpJme3UEoB?= M2LQNFIzPTFyNU[w
U2OS M2\NcmZ2dmO2aX;uJGF{e2G7 NIDoO4IyKML3TR?= NWLWb5R7OjRiaB?= NVu1WnhE[WK{b3fheIV{KG:oIHPlcIwh[3mlbHWgZZJz\XO2wrC= NEDEU2IzOjVzMEW2NC=>

... Click to View More Cell Line Experimental Data

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:
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
Synonyms N/A

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Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT01870596 Completed Adult Acute Megakaryoblastic Leukemia|Adult Acute Monoblastic Leukemia|Adult Acute Monocytic Leukemia|Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11|Adult Acute Myeloid Leukemia With Maturation|Adult Acute Myeloid Leukemia With Minimal Differentiation|Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11|Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1|Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL|Adult Acute Myeloid Leukemia Without Maturation|Adult Acute Myelomonocytic Leukemia|Adult Erythroleukemia|Adult Pure Erythroid Leukemia|Alkylating Agent-Related Acute Myeloid Leukemia|Recurrent Adult Acute Myeloid Leukemia National Cancer Institute (NCI) May 2013 Phase 2
NCT00907517 Terminated Myelogenous Leukemia, Acute|Leukemia, Lymphocytic, Acute|Leukemia, Lymphoblastic, Acute, Philadelphia-Positive|Myelogenous Leukemia, Chronic, Aggressive Phase Merck Sharp & Dohme Corp. July 2009 Phase 1
NCT00779584 Completed Hodgkin Disease|Lymphoma, Non-Hodgkin|Neoplasms Merck Sharp & Dohme Corp. October 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

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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