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

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 NHvMbVdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mlj0NlAxNzJyMECgcm0> NITpO2UzPCCq NF\YXYhl\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= MWOyOFM2QTV{Nh?=
HCT115 NYnQT|JMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHexcJkzODBxMkCwNEBvVQ>? NEnMNmkzPCCq NUTsWpM6\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l Ml;qNlQ{PTl3Mk[=
SW620 MlnpS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NW\KbY1kOjByL{KwNFAhdk1? NWLy[G4{OjRiaB?= Ml;j[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n MWiyOFM2QTV{Nh?=
IGROV-1 MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWOyNFAwOjByMDDuUS=> MmGzNlQhcA>? NGS1OpVl\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= M{fyd|I1OzV7NUK2
HCT116 MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3mwVlIxOC9{MECwJI5O NXTNZYlSOjRiaB?= M{K1XoRm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= MkfvNlQ{PTl3Mk[=
MCF10A NYrUZpFYT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIjXNJYzODBxMkCwNEBvVQ>? M1jQVVI1KGh? NWPLS3dK\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l MlOzNlQ{PTl3Mk[=
MiaPaCa-2 NGTLdZNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYWyNFAwOjByMDDuUS=> NUP1dFY1OjRiaB?= M1:4U4Rm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= MX6yOFM2QTV{Nh?=
MDA-MB-231 M2CzbGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXruVoR7OjByL{KwNFAhdk1? M2G3e|I1KGh? MlTv[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n NWfqWYI3OjR|NUm1NlY>
HCC2998 M2LGcGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1TONlIxOC9{MECwJI5O MnmwNlQhcA>? NFnRR2Nl\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= MmruNlQ{PTl3Mk[=
U87 NGDpOlJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFLXTJMzODBxMkCwNEBvVQ>? MYqyOEBp MYfk[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? NIXMW5gzPDN3OUWyOi=>
MDA-MB-435 M4j5ZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Ml\5NlAxNzJyMECgcm0> MoiyNlQhcA>? M4O4U4Rm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= NITwd28zPDN3OUWyOi=>
SNB19 MkLoS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1X3U|IxOC9{MECwJI5O M3TtT|I1KGh? M{LpS4Rm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= M2jWclI1OzV7NUK2
U20S M{\Uemdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NX\HXYJoOjByL{KwNFAhdk1? NX72TZBCOjRiaB?= NIfvdVhl\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= NXTDR3cxOjR|NUm1NlY>
A498 MkH0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFTIe44zODBxMkCwNEBvVQ>? NX\OXFZiOjRiaB?= NFfuWHVl\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= NVPaWHA3OjR|NUm1NlY>
TK10 M2S4RWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlKyNlAxNzJyMECgcm0> M{HqZlI1KGh? M{H4WoRm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= MmTmNlQ{PTl3Mk[=
AsPC-1 NFXzZ2dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MX6yNFAwOjByMDDuUS=> MkfVNlQhcA>? NVq0fllC\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l NIjKepozPDN3OUWyOi=>
H23 MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1i4VlUxOCCwTR?= MlH1NlQhcA>? M4PnVmROW09? MUnlcohidmOnczD0bIUh[2inbX;z[Y5{cXSrenH0bY9vKHSxIGDNXC=> NYHhcoZpOjRzMUO1OFk>
H1437 M{O5W2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFu0UVU2ODBibl2= MoLrNlQhcA>? M{XVU2ROW09? Mlf2[Y5p[W6lZYOgeIhmKGOqZX3vd4Vve2m2aYrheIlwdiC2bzDQUXg> MVSyOFEyOzV2OR?=
H1993 MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NY\kc2RmPTByIH7N NUXTSVVEOjRiaB?= NH;Sb45FVVOR NEflcmNmdmijbnPld{B1cGViY3jlcY9{\W6|aYTpfoF1cW:wIITvJHBOYA>? NUDvWlRWOjRzMUO1OFk>
H1299 M1HuXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWDjO5BbPTByIH7N M17mU|I1KGh? NGTFVYhFVVOR NYXl[XJr\W6qYX7j[ZMhfGinIHPo[Y1we2Wwc3n0bZpifGmxbjD0c{BRVVh? NEfKZWczPDFzM{W0PS=>
AsPC-1 MkD6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlfGNVAuOTByMDDuUS=> MYmyOE01QGh? Mn:3[Y5p[W6lZYOgeIhmKGOqZX3vd4Vve2m2aYrheIlwdiC2bzDn[Y1kcXSjYnnu[S=> MWiyN|gxPDR{Mh?=
MiaPaCa-2 MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGfze4gyOC1zMECwJI5O M2TES|I1NTR6aB?= MnHt[Y5p[W6lZYOgeIhmKGOqZX3vd4Vve2m2aYrheIlwdiC2bzDn[Y1kcXSjYnnu[S=> NYT1SW51OjN6MES0NlI>
BxPC-3 NGOwNIxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXT4fnRxOTBvMUCwNEBvVQ>? MkT4NlQuPDiq MkLQ[Y5p[W6lZYOgeIhmKGOqZX3vd4Vve2m2aYrheIlwdiC2bzDn[Y1kcXSjYnnu[S=> MmTVNlM5ODR2MkK=
SKOV3 NX3xe4ZZT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXzYOJB1OC5|INM1US=> MYi4JIQ> M3;0XpNmdnOrdHn6[ZMhfGinIHPlcIwhdGmwZYOgeI8h\2WvY3n0ZYJqdmYEoB?= MWSyN|U1QDJ4OR?=
OVCAR-8 NIT1ZXdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NI\n[Y8xNjNiwsXN M4LvWVgh\A>? NFTZd4h{\W6|aYTpfoV{KHSqZTDj[YxtKGyrbnXzJJRwKGenbXPpeIFjcW6nwrC= M{XBeFI{PTR6Mk[5
MV-4-11 NE\VTIRCeG:ydH;zbZMhSXO|YYm= MlXrNVAxNTdyMDDuUS=> M3LEUlQ5KGh? M2\pOIlv\HWlZYOgZZBweHSxc3nzJIRwe2ViZHXw[Y5l\W62bIm= NYXEc491OjN3M{[3NlE>
U937 NYLX[plxSXCxcITvd4l{KEG|c3H5 MmDoNVAxNTdyMDDuUS=> MlniOFghcA>? NVLHcZpVcW6mdXPld{BieG:ydH;zbZMh\G:|ZTDk[ZBmdmSnboTsfS=> MViyN|U{Pjd{MR?=
MOLM-13  NIDWdpVCeG:ydH;zbZMhSXO|YYm= M4XiXVExOC15MECgcm0> M1TZR|Q5KGh? NGq2T3hqdmS3Y3XzJIFxd3C2b4Ppd{Bld3OnIHTldIVv\GWwdHz5 M2TLNVI{PTN4N{Kx
A2058  MnPkR4VtdCCYaXHibYxqfHliQYPzZZk> NV;wbZZkOzdwNT2zNFAhdk1? NH;ZdmY4OiCq NFjoRmdFVVOR MVfy[YR2[2W|IITo[UBOUy1zN{e1JGVEPTEEoHL5JFUu\m:uZDD0c{BidiCjdnXyZYdmKG:oIES1JI5O MoDoNlMyPDh4OES=
H2009 MojOR4VtdCCYaXHibYxqfHliQYPzZZk> NFO4OXk2ODBibl2= NHG2VVI4OiCq MVrEUXNQ NF7pS3Jz\XO3bITzJIlvKEdzL2OtdIhie2ViYXPjeY12dGG2aX;uJINwdWKrbnXkJJdqfGhiTVutNVc4PQ>? NHzHUWozOzF2OE[4OC=>
Su.86.86 NHPuVIVE\WyuIG\pZYJqdGm2eTDBd5NigQ>? NGrZW5A2ODBibl2= MnLhO|IhcA>? NYrZPFlCTE2VTx?= MnLEdoV{fWy2czDpckBIOS:VLYDoZZNmKGGlY4XteYxifGmxbjDjc41jcW6nZDD3bZRpKE2NLUG3O|U> MoW0NlMyPDh4OES=
HRE MonOR4VtdCCYaXHibYxqfHliQYPzZZk> MnjCOVAxKG6P MV[3NkBp MmfQSG1UVw>? MXjy[ZN2dHS|IHnuJGcyN1NvcHjhd4Uh[WOldX31cIF1cW:wIHPvcYJqdmWmIIfpeIghVUtvMUe3OS=> NFv5bXIzOzF2OE[4OC=>
HMEC NYTTd2d5S2WubDDWbYFjcWyrdImgRZN{[Xl? M3P6fVUxOCCwTR?= NXjqU5NpPzJiaB?= NWLkeWFrTE2VTx?= NVTyUGtGemW|dXz0d{BqdiCJMT;TMZBp[XOnIHHjZ5VufWyjdHnvckBkd22kaX7l[EB4cXSqIF3LMVE4PzV? NVXSOYw3OjNzNEi2PFQ>
U2OS  NEL2SpJHfW6ldHnvckBCe3OjeR?= M{nM[FIhyrWP M17SZlAuOjRiaB?= M3;RUYlv\HWlZYOgdIhwe3Cqb4L5cIF1cW:wIH;mJGNpczFiYYSgd4VzcW6nIEO0OUBifCCkb4ToJINwdmOnboTyZZRqd26|IHHzJIViemy7IHHzJFIhcCCjZoTldkBi\G2rbnnzeJJifGmxbh?= Mn;XNlI6OzdzNEe=
U2OS  NVTQbm5MT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NX7xfYxWOC1zMDFCuW0> M2nKSFI1NzR6IHi= NWq4[5locW6qaXLpeJMh[2WubDDndo94fGhiZH;z[UBl\XCnbnTlcpRtgQ>? NF3P[VEzOjl|N{G0Oy=>
U937 Mkf1SpVv[3Srb36gRZN{[Xl? NWOxdZU{OTByLUWwNEBvVQ>? NEjMTZM1KGkEoB?= NV;HSJlK\GWlcnXhd4V{KHSqZTDjfZRiemGkaX7lMYlv\HWlZXSgR4hsOSCjdYTvdIhwe3Cqb4L5cIF1cW:wIHH0JHNmejJ7NtMgZY5lKHC{ZY\lcpR{KEOmY{K1RUBld3ewcnXneYxifGmxbh?= NEnhS44zOjh4OUi2PS=>
U937 MmmxSpVv[3Srb36gRZN{[Xl? NGHs[|EyODBibl2= NWK2fI1jPCCqwrC= M4fFPJJmfmW{c3XzJJRp\SCleYThdoFjcW6nLXnu[JVk\WRiaX7obYJqfGmxbjDv[uKhO0hvdHj5cYllcW6nIHnuZ49zeG:{YYTpc44hcW62bzDEUmE> MkHRNlI5Pjl6Nkm=
U937 NXXN[pQ3TnWwY4Tpc44hSXO|YYm= NHXuR3YyODBvNUCwJI5O M3zHfVQhcMLi MXHpcoR2[2W|IHnuZ5Jm[XOnZDDwbI9{eGixconsZZRqd25ib3[gTFJCYA>? NFT6VpozOjh4OUi2PS=>
HL-60 MWLBdI9xfG:|aYOgRZN{[Xl? NWf3eHI4OzBxMUCwM|MxOCCwTR?= M1nkS|I1KGh? NVfPeWFETE2VTx?= M{nZTYVvcGGwY3XzJIN6fGG{YXLpcoUucW6mdXPl[EBieG:ydH;zbZM> Mn30NlI5Pjl6Nkm=
ML-1 Moq3RZBweHSxc3nzJGF{e2G7 NIDEdGMzPS93MD:xNFAhdk1? M2LqZ|I1KGh? Mn7zSG1UVw>? NUK3SnF{\W6qYX7j[ZMh[3m2YYLhZolv\S2rbnT1Z4VlKGGyb4D0c5Nqew>? MoPzNlI5Pjl6Nkm=
HCT116 NVTUbGNFTnWwY4Tpc44hSXO|YYm= M{nCSVEhyrWP M2LVXFI1KGh? NInwR4Zi[nKxZ3H0[ZMhd2ZiY3XscEBkgWOuZTDhdpJme3UEoB?= NFnzZnAzOjVzMEW2NC=>
U2OS NYPONXBLTnWwY4Tpc44hSXO|YYm= NHHye4gyKML3TR?= NHTFRYozPCCq MmTPZYJzd2ejdHXzJI9nKGOnbHygZ5lkdGViYYLy[ZN1yqB? Mkn6NlI2OTB3NkC=

... 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 individually and in order:
4% DMSO+30% propylene glycol
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