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 M2PmWmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYHmXWVnOjByL{KwNFAhdk1? MoDFNlQhcA>? NUSxR3Q3\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l NWDWPYpoOjR|NUm1NlY>
HCT115 NYnSRmNmT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYTq[lE1OjByL{KwNFAhdk1? NELPdYwzPCCq MX3k[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? M{HCXlI1OzV7NUK2
SW620 NHnlboJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MViyNFAwOjByMDDuUS=> NHqwe|gzPCCq NE[ycnBl\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= NH:1cXEzPDN3OUWyOi=>
IGROV-1 MmC2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3nPeFIxOC9{MECwJI5O MX6yOEBp M4rnfYRm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= MlnhNlQ{PTl3Mk[=
HCT116 MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX62W2N2OjByL{KwNFAhdk1? MXGyOEBp MWHk[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? NF23dWEzPDN3OUWyOi=>
MCF10A NGTSTXhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFLWdJEzODBxMkCwNEBvVQ>? NXyzNGs3OjRiaB?= MXXk[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? NF;i[3QzPDN3OUWyOi=>
MiaPaCa-2 MnvnS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVOyNFAwOjByMDDuUS=> NF25e5UzPCCq M1z3VoRm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= NIHQVoIzPDN3OUWyOi=>
MDA-MB-231 M4fBeGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MW[yNFAwOjByMDDuUS=> MWKyOEBp NV;mUFFo\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l NFG0bZAzPDN3OUWyOi=>
HCC2998 M3vsVmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGHnWXQzODBxMkCwNEBvVQ>? M2T0d|I1KGh? Mlnw[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n MoflNlQ{PTl3Mk[=
U87 MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGjVSJczODBxMkCwNEBvVQ>? MV2yOEBp Ml;B[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n M1zuW|I1OzV7NUK2
MDA-MB-435 MoXzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NG\RXIQzODBxMkCwNEBvVQ>? M{jxVFI1KGh? NF\xeo9l\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= MnXkNlQ{PTl3Mk[=
SNB19 NELsXoZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MV[yNFAwOjByMDDuUS=> M1r5flI1KGh? NWjHVVJD\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l MWCyOFM2QTV{Nh?=
U20S NVW2[4ZbT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoTkNlAxNzJyMECgcm0> NHTEOY4zPCCq Mn7z[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n MlfSNlQ{PTl3Mk[=
A498 MlG5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MofwNlAxNzJyMECgcm0> NIrvTWwzPCCq MX;k[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? NV\SVpJsOjR|NUm1NlY>
TK10 M{HUdmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHvUWmszODBxMkCwNEBvVQ>? M1rsUFI1KGh? MmDL[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n NVywUGZyOjR|NUm1NlY>
AsPC-1 MnXOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYKyNFAwOjByMDDuUS=> NIHNOoMzPCCq M13HUIRm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= NXLNcHpGOjR|NUm1NlY>
H23 M4PGPGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWO1NFAhdk1? MVGyOEBp M2O4OWROW09? NImyR|ZmdmijbnPld{B1cGViY3jlcY9{\W6|aYTpfoF1cW:wIITvJHBOYA>? NEfyXWgzPDFzM{W0PS=>
H1437 NFrqU5hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVe1NFAhdk1? MUiyOEBp MkG1SG1UVw>? Mnr5[Y5p[W6lZYOgeIhmKGOqZX3vd4Vve2m2aYrheIlwdiC2bzDQUXg> MonqNlQyOTN3NEm=
H1993 MYrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnfqOVAxKG6P NUHKfZd5OjRiaB?= NHXablZFVVOR MlLi[Y5p[W6lZYOgeIhmKGOqZX3vd4Vve2m2aYrheIlwdiC2bzDQUXg> NGLOOpkzPDFzM{W0PS=>
H1299 MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEfWOHQ2ODBibl2= M2\OXFI1KGh? M{jKfWROW09? NVPLSYJO\W6qYX7j[ZMhfGinIHPo[Y1we2Wwc3n0bZpifGmxbjD0c{BRVVh? Mn7hNlQyOTN3NEm=
AsPC-1 M{C2Tmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmW0NVAuOTByMDDuUS=> NF3kWZUzPC12OHi= NUPMdmln\W6qYX7j[ZMhfGinIHPo[Y1we2Wwc3n0bZpifGmxbjD0c{Bo\W2laYThZolv\Q>? NXTJ[5JQOjN6MES0NlI>
MiaPaCa-2 NFnGOodIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEjKfFgyOC1zMECwJI5O MUiyOE01QGh? NYf4dItm\W6qYX7j[ZMhfGinIHPo[Y1we2Wwc3n0bZpifGmxbjD0c{Bo\W2laYThZolv\Q>? NWXXT4ZrOjN6MES0NlI>
BxPC-3 NHnvXlZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUPnUI92OTBvMUCwNEBvVQ>? NWHUbmtZOjRvNEjo MX3lcohidmOnczD0bIUh[2inbX;z[Y5{cXSrenH0bY9vKHSxIHflcYNqfGGkaX7l M3LTblI{QDB2NEKy
SKOV3 M2HlRWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NETFXXcxNjNiwsXN M4HqZVgh\A>? M3LlRpNmdnOrdHn6[ZMhfGinIHPlcIwhdGmwZYOgeI8h\2WvY3n0ZYJqdmYEoB?= NV6zWlNZOjN3NEiyOlk>
OVCAR-8 M1vEWGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVKwMlMhyrWP M2\aUVgh\A>? MUTz[Y5{cXSrenXzJJRp\SClZXzsJIxqdmW|IITvJIdmdWOrdHHibY5myqB? NUmxNphjOjN3NEiyOlk>
MV-4-11 NVrNPFE{SXCxcITvd4l{KEG|c3H5 M2jTdlExOC15MECgcm0> NVOzeYJZPDhiaB?= MlHjbY5lfWOnczDhdI9xfG:|aYOg[I9{\SCmZYDlcoRmdnSueR?= NX[zPHRZOjN3M{[3NlE>
U937 NH\SXmZCeG:ydH;zbZMhSXO|YYm= M4DUWVExOC15MECgcm0> Ml3FOFghcA>? Ml76bY5lfWOnczDhdI9xfG:|aYOg[I9{\SCmZYDlcoRmdnSueR?= MmG3NlM2OzZ5MkG=
MOLM-13  NYnk[GQzSXCxcITvd4l{KEG|c3H5 MoXQNVAxNTdyMDDuUS=> MmPJOFghcA>? M4n0NYlv\HWlZYOgZZBweHSxc3nzJIRwe2ViZHXw[Y5l\W62bIm= MXqyN|U{Pjd{MR?=
A2058  MXfD[YxtKF[rYXLpcIl1gSCDc4PhfS=> MnTWN|cvPS1|MECgcm0> MmqyO|IhcA>? NU\XNnVlTE2VTx?= NIDyd4dz\WS3Y3XzJJRp\SCPSz2xO|c2KEWFNUFCpIJ6KDVvZn;s[EB1dyCjbjDheoVz[WenIH;mJFQ2KG6P MVmyN|E1QDZ6NB?=
H2009 MYfD[YxtKF[rYXLpcIl1gSCDc4PhfS=> M3HGVFUxOCCwTR?= M2r1WVczKGh? MXHEUXNQ MWLy[ZN2dHS|IHnuJGcyN1NvcHjhd4Uh[WOldX31cIF1cW:wIHPvcYJqdmWmIIfpeIghVUtvMUe3OS=> NXrGOGk1OjNzNEi2PFQ>
Su.86.86 MXHD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NVHRWndPPTByIH7N Mnn0O|IhcA>? NH\ROZNFVVOR MnvZdoV{fWy2czDpckBIOS:VLYDoZZNmKGGlY4XteYxifGmxbjDjc41jcW6nZDD3bZRpKE2NLUG3O|U> NX3OUGVoOjNzNEi2PFQ>
HRE NXT4U3dwS2WubDDWbYFjcWyrdImgRZN{[Xl? NXfDc5JTPTByIH7N NIHiUGc4OiCq M4fTcGROW09? NVzNNXl{emW|dXz0d{BqdiCJMT;TMZBp[XOnIHHjZ5VufWyjdHnvckBkd22kaX7l[EB4cXSqIF3LMVE4PzV? NYjlb5UyOjNzNEi2PFQ>
HMEC M3rW[WNmdGxiVnnhZoltcXS7IFHzd4F6 NGDnR2Q2ODBibl2= NG\tcGU4OiCq MWTEUXNQ NX\mcmJzemW|dXz0d{BqdiCJMT;TMZBp[XOnIHHjZ5VufWyjdHnvckBkd22kaX7l[EB4cXSqIF3LMVE4PzV? M3P2e|I{OTR6Nki0
U2OS  MlPuSpVv[3Srb36gRZN{[Xl? MXKyJOK2VQ>? MojxNE0zPCCq MojGbY5lfWOnczDwbI9{eGixconsZZRqd25ib3[gR4hsOSCjdDDz[ZJqdmViM{S1JIF1KGKxdHigZ49v[2WwdILheIlwdnNiYYOg[YFzdHliYYOgNkBpKGGodHXyJIFldWmwaYP0doF1cW:w NV[5TVdtOjJ7M{exOFc>
U2OS  NIr0U|hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2nzWFAuOTBiwsXN NY[4OZB7OjRxNEigbC=> NHTxT4NqdmirYnn0d{Bk\WyuIHfyc5d1cCCmb4PlJIRmeGWwZHXueIx6 NUPGZ3NsOjJ7M{exOFc>
U937 M13tfGZ2dmO2aX;uJGF{e2G7 NHqzV|cyODBvNUCwJI5O NXXnbXRIPCCqwrC= MYXk[YNz\WG|ZYOgeIhmKGO7dHHyZYJqdmVvaX7keYNm\CCFaHuxJIF2fG:yaH;zdIhwenmuYYTpc44h[XRiU3XyNlk3yqCjbnSgdJJmfmWwdIOgR4RkOjWDIHTve45z\We3bHH0bY9v Mlz2NlI5Pjl6Nkm=
U937 NIOyfGlHfW6ldHnvckBCe3OjeR?= NUXBWIxvOTByIH7N M4PEXFQhcMLi NHPsUoZz\X[ncoPld{B1cGViY4n0ZZJi[mmwZT3pcoR2[2WmIHnubIljcXSrb36gc4bDqDOKLYTofY1q\GmwZTDpcoNwenCxcnH0bY9vKGmwdH:gSG5C M1K5NVIzQDZ7OE[5
U937 M3TXOGZ2dmO2aX;uJGF{e2G7 NGmxUGcyODBvNUCwJI5O NV2zOFVtPCCqwrC= MUnpcoR2[2W|IHnuZ5Jm[XOnZDDwbI9{eGixconsZZRqd25ib3[gTFJCYA>? NHzNXHEzOjh4OUi2PS=>
HL-60 MmT3RZBweHSxc3nzJGF{e2G7 NHSybZI{OC9zMECvN|AxKG6P MlrWNlQhcA>? MXrEUXNQ MonY[Y5p[W6lZYOgZ5l1[XKjYnnu[U1qdmS3Y3XkJIFxd3C2b4Ppdy=> NV:wVXdQOjJ6Nkm4Olk>
ML-1 NEO5UoVCeG:ydH;zbZMhSXO|YYm= MXGyOU82OC9zMECgcm0> MkTYNlQhcA>? NYPRbI9oTE2VTx?= NW[3TlJG\W6qYX7j[ZMh[3m2YYLhZolv\S2rbnT1Z4VlKGGyb4D0c5Nqew>? M2SwUVIzQDZ7OE[5
HCT116 NVXy[4x{TnWwY4Tpc44hSXO|YYm= MlPCNUDDvU1? M1K3c|I1KGh? MY\hZpJw\2G2ZYOgc4Yh[2WubDDjfYNt\SCjcoLld5TDqA>? MY[yNlUyODV4MB?=
U2OS M{SwWWZ2dmO2aX;uJGF{e2G7 MmrENUDDvU1? NHe1PXYzPCCq M4n3doFjem:pYYTld{Bw\iClZXzsJIN6[2ynIHHydoV{fMLi MnjENlI2OTB3NkC=

... 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