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 M{\Zdmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4DMd|IxOC9{MECwJI5O NILOSmEzPCCq NWTpb|hx\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l MVeyOFM2QTV{Nh?=
HCT115 NUXBflhTT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4PydFIxOC9{MECwJI5O MX2yOEBp NUHWdZoy\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l M{[4[FI1OzV7NUK2
SW620 NF\1cWZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVHmeo94OjByL{KwNFAhdk1? NH7NOWkzPCCq MYHk[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? NWfpXY5uOjR|NUm1NlY>
IGROV-1 NFfTb4pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3;FdVIxOC9{MECwJI5O NIXJNGYzPCCq NV[xVGM{\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l M3r5XFI1OzV7NUK2
HCT116 MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHLQ[lUzODBxMkCwNEBvVQ>? M4DHO|I1KGh? MmnB[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n NEf4flAzPDN3OUWyOi=>
MCF10A MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUiyNFAwOjByMDDuUS=> NVq0SFZZOjRiaB?= NHXlRnll\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= M1\hTlI1OzV7NUK2
MiaPaCa-2 NHzHOJlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmTzNlAxNzJyMECgcm0> MV:yOEBp MXXk[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? MUSyOFM2QTV{Nh?=
MDA-MB-231 NETDWlRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoXrNlAxNzJyMECgcm0> NWHiRotjOjRiaB?= MWnk[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? MWCyOFM2QTV{Nh?=
HCC2998 NUTHemNkT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnXrNlAxNzJyMECgcm0> MoDyNlQhcA>? MXLk[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? M2DBWlI1OzV7NUK2
U87 NHLTOndIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MY[yNFAwOjByMDDuUS=> MoTQNlQhcA>? NFzHNVhl\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= MlPPNlQ{PTl3Mk[=
MDA-MB-435 MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXiyNFAwOjByMDDuUS=> M3HqUFI1KGh? NInDXY9l\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= NWDqT3lQOjR|NUm1NlY>
SNB19 NFmxcWVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXHXd2F2OjByL{KwNFAhdk1? M4X4NFI1KGh? NHzyWItl\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= MUKyOFM2QTV{Nh?=
U20S MVzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVmyNFAwOjByMDDuUS=> NXjWXVQ{OjRiaB?= MVXk[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? MmS1NlQ{PTl3Mk[=
A498 MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1frbFIxOC9{MECwJI5O NEfEcpAzPCCq MWfk[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? MYSyOFM2QTV{Nh?=
TK10 M1zYUWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NW[3fmhDOjByL{KwNFAhdk1? NX\ITZpZOjRiaB?= NEX0S|dl\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= Mkj1NlQ{PTl3Mk[=
AsPC-1 M3vGSWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYqyNFAwOjByMDDuUS=> M1j1[lI1KGh? MoS1[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n M4rVPVI1OzV7NUK2
H23 NEn2WGJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWm1NFAhdk1? MXiyOEBp MnX2SG1UVw>? MYXlcohidmOnczD0bIUh[2inbX;z[Y5{cXSrenH0bY9vKHSxIGDNXC=> M2PkRVI1OTF|NUS5
H1437 NF7LSpFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mnr3OVAxKG6P NX\oS21lOjRiaB?= MmXESG1UVw>? NUfvS3ZS\W6qYX7j[ZMhfGinIHPo[Y1we2Wwc3n0bZpifGmxbjD0c{BRVVh? M3;a[FI1OTF|NUS5
H1993 NHqwdmNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHvxOpA2ODBibl2= NFv5UmYzPCCq MUfEUXNQ NUjieo55\W6qYX7j[ZMhfGinIHPo[Y1we2Wwc3n0bZpifGmxbjD0c{BRVVh? M{m0RlI1OTF|NUS5
H1299 MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4D5c|UxOCCwTR?= NEPpSYYzPCCq NX31O5pJTE2VTx?= M4Toc4VvcGGwY3XzJJRp\SClaHXtc5NmdnOrdHn6ZZRqd25idH:gVG1Z MWCyOFEyOzV2OR?=
AsPC-1 Mo\NS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2i4[FExNTFyMECgcm0> Mk\TNlQuPDiq M4HtWIVvcGGwY3XzJJRp\SClaHXtc5NmdnOrdHn6ZZRqd25idH:g[4Vu[2m2YXLpcoU> NGDVZ|AzOzhyNESyNi=>
MiaPaCa-2 NWnOWlQzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXmxNE0yODByIH7N M4LX[FI1NTR6aB?= MVjlcohidmOnczD0bIUh[2inbX;z[Y5{cXSrenH0bY9vKHSxIHflcYNqfGGkaX7l M{nBUFI{QDB2NEKy
BxPC-3 NUTsOXpiT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3jqV|ExNTFyMECgcm0> NIO1Z4gzPC12OHi= M{DmR4VvcGGwY3XzJJRp\SClaHXtc5NmdnOrdHn6ZZRqd25idH:g[4Vu[2m2YXLpcoU> MoH3NlM5ODR2MkK=
SKOV3 M1jZN2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHjtTWsxNjNiwsXN M{jTN|gh\A>? M{fIbJNmdnOrdHn6[ZMhfGinIHPlcIwhdGmwZYOgeI8h\2WvY3n0ZYJqdmYEoB?= MVqyN|U1QDJ4OR?=
OVCAR-8 NU\INpdsT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1fNcVAvOyEEtV2= M4ewTlgh\A>? NXG2eWMze2Wwc3n0bZpmeyC2aHWgZ4VtdCCuaX7ld{B1dyCpZX3jbZRi[mmwZdMg NGrtNHEzOzV2OEK2PS=>
MV-4-11 NUXaT2lwSXCxcITvd4l{KEG|c3H5 NFnzb4MyODBvN{CwJI5O NH:3WlE1QCCq MX;pcoR2[2W|IHHwc5B1d3OrczDkc5NmKGSncHXu[IVvfGy7 MYmyN|U{Pjd{MR?=
U937 MV;BdI9xfG:|aYOgRZN{[Xl? NFvYU3IyODBvN{CwJI5O MoDxOFghcA>? MY\pcoR2[2W|IHHwc5B1d3OrczDkc5NmKGSncHXu[IVvfGy7 M2[4eFI{PTN4N{Kx
MOLM-13  MYXBdI9xfG:|aYOgRZN{[Xl? NIXjWYwyODBvN{CwJI5O NFTBXGE1QCCq NUP1cJBNcW6mdXPld{BieG:ydH;zbZMh\G:|ZTDk[ZBmdmSnboTsfS=> MXqyN|U{Pjd{MR?=
A2058  MkjXR4VtdCCYaXHibYxqfHliQYPzZZk> M4DsZ|M4NjVvM{CwJI5O MluyO|IhcA>? M4DlVGROW09? NYPsc2x4emWmdXPld{B1cGViTVutNVc4PSCHQ{WwxsBjgSB3LX\vcIQhfG9iYX6gZZZmemGpZTDv[kA1PSCwTR?= NWDXZ4w3OjNzNEi2PFQ>
H2009 MmH1R4VtdCCYaXHibYxqfHliQYPzZZk> M{e3UVUxOCCwTR?= NUKwe3VwPzJiaB?= M2fLOmROW09? MlHCdoV{fWy2czDpckBIOS:VLYDoZZNmKGGlY4XteYxifGmxbjDjc41jcW6nZDD3bZRpKE2NLUG3O|U> M2\MSFI{OTR6Nki0
Su.86.86 NVra[VZSS2WubDDWbYFjcWyrdImgRZN{[Xl? NWXkZnQzPTByIH7N NULmbIRtPzJiaB?= NX31cZpYTE2VTx?= NG\JNWdz\XO3bITzJIlvKEdzL2OtdIhie2ViYXPjeY12dGG2aX;uJINwdWKrbnXkJJdqfGhiTVutNVc4PQ>? M3TnSlI{OTR6Nki0
HRE MoD0R4VtdCCYaXHibYxqfHliQYPzZZk> M3vJbFUxOCCwTR?= MnnWO|IhcA>? M1vxOmROW09? NGXn[5Rz\XO3bITzJIlvKEdzL2OtdIhie2ViYXPjeY12dGG2aX;uJINwdWKrbnXkJJdqfGhiTVutNVc4PQ>? NHPRSW8zOzF2OE[4OC=>
HMEC NXT5UI81S2WubDDWbYFjcWyrdImgRZN{[Xl? MoO5OVAxKG6P MXO3NkBp MmjuSG1UVw>? MYTy[ZN2dHS|IHnuJGcyN1NvcHjhd4Uh[WOldX31cIF1cW:wIHPvcYJqdmWmIIfpeIghVUtvMUe3OS=> NV\zN|JWOjNzNEi2PFQ>
U2OS  NEDZPJFHfW6ldHnvckBCe3OjeR?= Mmq4NkDDvU1? MYSwMVI1KGh? MoTSbY5lfWOnczDwbI9{eGixconsZZRqd25ib3[gR4hsOSCjdDDz[ZJqdmViM{S1JIF1KGKxdHigZ49v[2WwdILheIlwdnNiYYOg[YFzdHliYYOgNkBpKGGodHXyJIFldWmwaYP0doF1cW:w M4\3ZlIzQTN5MUS3
U2OS  M1n4bWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NILMVJIxNTFyINM1US=> NFHpOlYzPC92ODDo MlvmbY5pcWKrdIOgZ4VtdCCpcn;3eIgh\G:|ZTDk[ZBmdmSnboTsfS=> M2nifFIzQTN5MUS3
U937 NVn6R|A{TnWwY4Tpc44hSXO|YYm= NFzTdY8yODBvNUCwJI5O NGTpSJc1KGkEoB?= NXXpUllZ\GWlcnXhd4V{KHSqZTDjfZRiemGkaX7lMYlv\HWlZXSgR4hsOSCjdYTvdIhwe3Cqb4L5cIF1cW:wIHH0JHNmejJ7NtMgZY5lKHC{ZY\lcpR{KEOmY{K1RUBld3ewcnXneYxifGmxbh?= MX[yNlg3QTh4OR?=
U937 M3S4OGZ2dmO2aX;uJGF{e2G7 NUTxOWgyOTByIH7N NV\tRo83PCCqwrC= M3K5fZJmfmW{c3XzJJRp\SCleYThdoFjcW6nLXnu[JVk\WRiaX7obYJqfGmxbjDv[uKhO0hvdHj5cYllcW6nIHnuZ49zeG:{YYTpc44hcW62bzDEUmE> MnLmNlI5Pjl6Nkm=
U937 MmnnSpVv[3Srb36gRZN{[Xl? NHLmdlkyODBvNUCwJI5O NXX6[oU4PCCqwrC= NGSzSIdqdmS3Y3XzJIlv[3KnYYPl[EBxcG:|cHjvdplt[XSrb36gc4YhUDKDWB?= M4HoUFIzQDZ7OE[5
HL-60 MVnBdI9xfG:|aYOgRZN{[Xl? Mk\jN|AwOTByL{OwNEBvVQ>? NYLCSYpTOjRiaB?= MmD0SG1UVw>? M{LuToVvcGGwY3XzJIN6fGG{YXLpcoUucW6mdXPl[EBieG:ydH;zbZM> Ml;QNlI5Pjl6Nkm=
ML-1 NYO4TpUxSXCxcITvd4l{KEG|c3H5 M2rmRVI2NzVyL{GwNEBvVQ>? Mon3NlQhcA>? NYPTOm5lTE2VTx?= Mn;p[Y5p[W6lZYOgZ5l1[XKjYnnu[U1qdmS3Y3XkJIFxd3C2b4Ppdy=> NFHmfFUzOjh4OUi2PS=>
HCT116 MULGeY5kfGmxbjDBd5NigQ>? NUHEO4pmOSEEtV2= NWLhTpl4OjRiaB?= M{PVeYFjem:pYYTld{Bw\iClZXzsJIN6[2ynIHHydoV{fMLi NXHqeoRQOjJ3MUC1OlA>
U2OS MUHGeY5kfGmxbjDBd5NigQ>? NELTNoUyKML3TR?= MnfFNlQhcA>? MXHhZpJw\2G2ZYOgc4Yh[2WubDDjfYNt\SCjcoLld5TDqA>? M3;xUlIzPTFyNU[w

... 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(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

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Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT00907517 Terminated Myelogenous Leukemia Acute|Leukemia Lymphocytic Acute|Leukemia Lymphoblastic Acute Philadelphia-Positive|Myelogenous Leukemia Chronic Aggressive Phase Merck Sharp & Dohme Corp. July 29 2009 Phase 1
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
NCT01521299 Withdrawn Advanced Solid Tumors Dartmouth-Hitchcock Medical Center March 2012 Phase 1
NCT00779584 Completed 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.

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID