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 NVXGd3ZJT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH3CcYczODBxMkCwNEBvVQ>? NEjhT|czPCCq M4XB[YRm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= NV;Jc5pNOjR|NUm1NlY>
HCT115 MoS1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXzEc3hPOjByL{KwNFAhdk1? NWC0NpBrOjRiaB?= MYrk[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? NGrpPJEzPDN3OUWyOi=>
SW620 MoT0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3\je|IxOC9{MECwJI5O Mmm4NlQhcA>? NF\VbIJl\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= NVvS[oo1OjR|NUm1NlY>
IGROV-1 NVHGcpJpT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NV63TXk4OjByL{KwNFAhdk1? MX2yOEBp MWPk[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? NFrlR4gzPDN3OUWyOi=>
HCT116 MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1LLb|IxOC9{MECwJI5O NEfvfnUzPCCq MoHC[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n NWHuUJBWOjR|NUm1NlY>
MCF10A NEHjVXdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlGyNlAxNzJyMECgcm0> NYrmfJp{OjRiaB?= NUXmW3d2\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l MYOyOFM2QTV{Nh?=
MiaPaCa-2 MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVKyNFAwOjByMDDuUS=> M4PsUFI1KGh? Ml\K[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n MWqyOFM2QTV{Nh?=
MDA-MB-231 MWDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUGyNFAwOjByMDDuUS=> M{PrWlI1KGh? NEDjOVNl\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= Ml;6NlQ{PTl3Mk[=
HCC2998 M4fCdmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mn;uNlAxNzJyMECgcm0> Ml7ZNlQhcA>? MUnk[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? M3y4U|I1OzV7NUK2
U87 M1PtO2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYrhfpNYOjByL{KwNFAhdk1? NYDuXY1JOjRiaB?= M2XUXIRm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= Mlj0NlQ{PTl3Mk[=
MDA-MB-435 MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoW5NlAxNzJyMECgcm0> NX7xOGt6OjRiaB?= MY\k[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? NVPLXoZkOjR|NUm1NlY>
SNB19 NX;GdW5{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MW[yNFAwOjByMDDuUS=> MYCyOEBp NF62WXhl\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= NHTLZoMzPDN3OUWyOi=>
U20S MkniS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3XYblIxOC9{MECwJI5O MoCwNlQhcA>? NFrZWG5l\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= M4nLZ|I1OzV7NUK2
A498 MlHMS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{PPeVIxOC9{MECwJI5O NUD4XmE6OjRiaB?= NXTvNZRO\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l MlWyNlQ{PTl3Mk[=
TK10 MnH3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEH6fnkzODBxMkCwNEBvVQ>? M3PZeFI1KGh? MoPl[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n M4jzW|I1OzV7NUK2
AsPC-1 M{nKcWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXTpUoREOjByL{KwNFAhdk1? NILZUnozPCCq NWexO5BI\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l NI\2dWszPDN3OUWyOi=>
H23 MoPOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXXCd2xrPTByIH7N NHLQ[|YzPCCq NEP2d2lFVVOR NIrhPXNmdmijbnPld{B1cGViY3jlcY9{\W6|aYTpfoF1cW:wIITvJHBOYA>? NGHFS3YzPDFzM{W0PS=>
H1437 MXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoPyOVAxKG6P MlTDNlQhcA>? MljySG1UVw>? MoDQ[Y5p[W6lZYOgeIhmKGOqZX3vd4Vve2m2aYrheIlwdiC2bzDQUXg> Mlm0NlQyOTN3NEm=
H1993 Mn7HS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mlm5OVAxKG6P NH[4PJYzPCCq NGfDV2hFVVOR M{PYTIVvcGGwY3XzJJRp\SClaHXtc5NmdnOrdHn6ZZRqd25idH:gVG1Z NGHKR3IzPDFzM{W0PS=>
H1299 NETm[GNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHT6T2k2ODBibl2= NX7Hb25OOjRiaB?= MUDEUXNQ NVrWNHBl\W6qYX7j[ZMhfGinIHPo[Y1we2Wwc3n0bZpifGmxbjD0c{BRVVh? MYCyOFEyOzV2OR?=
AsPC-1 M2rPVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2HVS|ExNTFyMECgcm0> MUeyOE01QGh? Mlrs[Y5p[W6lZYOgeIhmKGOqZX3vd4Vve2m2aYrheIlwdiC2bzDn[Y1kcXSjYnnu[S=> NYPCfYRFOjN6MES0NlI>
MiaPaCa-2 NXz6SpZnT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVewPG57OTBvMUCwNEBvVQ>? M4K4[|I1NTR6aB?= NILHZ|ZmdmijbnPld{B1cGViY3jlcY9{\W6|aYTpfoF1cW:wIITvJIdmdWOrdHHibY5m NXHocWVSOjN6MES0NlI>
BxPC-3 NUnZcYpuT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIHhdW4yOC1zMECwJI5O M2CzWFI1NTR6aB?= NYjrZZpR\W6qYX7j[ZMhfGinIHPo[Y1we2Wwc3n0bZpifGmxbjD0c{Bo\W2laYThZolv\Q>? MYeyN|gxPDR{Mh?=
SKOV3 NVHVW3FZT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1fs[|AvOyEEtV2= NWX1[2NmQCCm NX;IdnNFe2Wwc3n0bZpmeyC2aHWgZ4VtdCCuaX7ld{B1dyCpZX3jbZRi[mmwZdMg MmL4NlM2PDh{Nkm=
OVCAR-8 MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVvNVVBKOC5|INM1US=> MVi4JIQ> NHXyfGh{\W6|aYTpfoV{KHSqZTDj[YxtKGyrbnXzJJRwKGenbXPpeIFjcW6nwrC= M1TlblI{PTR6Mk[5
MV-4-11 Mo\lRZBweHSxc3nzJGF{e2G7 NWDGZ4hwOTByLUewNEBvVQ>? MV20PEBp M{ex[4lv\HWlZYOgZZBweHSxc3nzJIRwe2ViZHXw[Y5l\W62bIm= NVWwOIJYOjN3M{[3NlE>
U937 MXPBdI9xfG:|aYOgRZN{[Xl? Ml7RNVAxNTdyMDDuUS=> MkLsOFghcA>? NYPSSlF4cW6mdXPld{BieG:ydH;zbZMh\G:|ZTDk[ZBmdmSnboTsfS=> M{PIelI{PTN4N{Kx
MOLM-13  NGXWZVNCeG:ydH;zbZMhSXO|YYm= NUHBR4FDOTByLUewNEBvVQ>? M{X3bVQ5KGh? MWrpcoR2[2W|IHHwc5B1d3OrczDkc5NmKGSncHXu[IVvfGy7 NELzeIwzOzV|NkeyNS=>
A2058  M3;mTWNmdGxiVnnhZoltcXS7IFHzd4F6 NGXzbm4{Py53LUOwNEBvVQ>? M1uwUFczKGh? MYHEUXNQ M1fOUpJm\HWlZYOgeIhmKE2NLUG3O|UhTUN3MNMgZpkhPS2ob3zkJJRwKGGwIHH2[ZJi\2Vib3[gOFUhdk1? M4LpNVI{OTR6Nki0
H2009 MXHD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NXuyeGtGPTByIH7N Mlr0O|IhcA>? MkK0SG1UVw>? MmPIdoV{fWy2czDpckBIOS:VLYDoZZNmKGGlY4XteYxifGmxbjDjc41jcW6nZDD3bZRpKE2NLUG3O|U> MVuyN|E1QDZ6NB?=
Su.86.86 M1LSeWNmdGxiVnnhZoltcXS7IFHzd4F6 NXzBT44xPTByIH7N NYHx[pI1PzJiaB?= MXzEUXNQ MUPy[ZN2dHS|IHnuJGcyN1NvcHjhd4Uh[WOldX31cIF1cW:wIHPvcYJqdmWmIIfpeIghVUtvMUe3OS=> M3vzNVI{OTR6Nki0
HRE MYnD[YxtKF[rYXLpcIl1gSCDc4PhfS=> Mn:xOVAxKG6P NWHyO2RiPzJiaB?= M3v4WmROW09? NX3jWIs4emW|dXz0d{BqdiCJMT;TMZBp[XOnIHHjZ5VufWyjdHnvckBkd22kaX7l[EB4cXSqIF3LMVE4PzV? MnPTNlMyPDh4OES=
HMEC NYSyUJU{S2WubDDWbYFjcWyrdImgRZN{[Xl? NXT4S2hSPTByIH7N MWq3NkBp M1fIXWROW09? MX\y[ZN2dHS|IHnuJGcyN1NvcHjhd4Uh[WOldX31cIF1cW:wIHPvcYJqdmWmIIfpeIghVUtvMUe3OS=> MkPZNlMyPDh4OES=
U2OS  NXS3O2hXTnWwY4Tpc44hSXO|YYm= M1jycFIhyrWP M{O5OlAuOjRiaB?= NYXNSI5TcW6mdXPld{BxcG:|cHjvdplt[XSrb36gc4YhS2itMTDheEB{\XKrbnWgN|Q2KGG2IHLveIgh[2:wY3XueJJifGmxboOgZZMh\WG{bImgZZMhOiCqIHHmeIVzKGGmbXnubZN1emG2aX;u MVuyNlk{PzF2Nx?=
U2OS  NETaZXhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NV;JellGOC1zMDFCuW0> MY[yOE81QCCq MWLpcohq[mm2czDj[YxtKGe{b4f0bEBld3OnIHTldIVv\GWwdHz5 NHvaTIMzOjl|N{G0Oy=>
U937 M2jTXGZ2dmO2aX;uJGF{e2G7 MlTNNVAxNTVyMDDuUS=> M1POPFQhcMLi Mo\M[IVkemWjc3XzJJRp\SCleYThdoFjcW6nLXnu[JVk\WRiQ3jrNUBifXSxcHjvd5Bpd3K7bHH0bY9vKGG2IGPldlI6PsLiYX7kJJBz\X[nboTzJGNl[zJ3QTDkc5dvemWpdXzheIlwdg>? MmPKNlI5Pjl6Nkm=
U937 MX;GeY5kfGmxbjDBd5NigQ>? NWTUPFZHOTByIH7N NYHFTIhiPCCqwrC= MVny[ZZmenOnczD0bIUh[3m2YYLhZolv\S2rbnT1Z4VlKGmwaHnibZRqd25ib3dCpFNJNXSqeX3p[Ilv\SCrbnPvdpBwemG2aX;uJIlvfG9iRF7B M4P5ZVIzQDZ7OE[5
U937 M1q3T2Z2dmO2aX;uJGF{e2G7 NWDjdXBnOTByLUWwNEBvVQ>? NEO2coQ1KGkEoB?= Ml7ubY5lfWOnczDpcoNz\WG|ZXSgdIhwe3Cqb4L5cIF1cW:wIH;mJGgzSVh? NFzKPZMzOjh4OUi2PS=>
HL-60 M1WydmFxd3C2b4Ppd{BCe3OjeR?= NFLnSWY{OC9zMECvN|AxKG6P MmS1NlQhcA>? NGryUVNFVVOR MoHY[Y5p[W6lZYOgZ5l1[XKjYnnu[U1qdmS3Y3XkJIFxd3C2b4Ppdy=> NX7aNpVEOjJ6Nkm4Olk>
ML-1 NHj5dmdCeG:ydH;zbZMhSXO|YYm= MXuyOU82OC9zMECgcm0> M2X1fVI1KGh? NG\kW41FVVOR Ml3o[Y5p[W6lZYOgZ5l1[XKjYnnu[U1qdmS3Y3XkJIFxd3C2b4Ppdy=> NFzBcWkzOjh4OUi2PS=>
HCT116 NWPCPVZPTnWwY4Tpc44hSXO|YYm= MkXhNUDDvU1? M3nRbFI1KGh? NELO[XFi[nKxZ3H0[ZMhd2ZiY3XscEBkgWOuZTDhdpJme3UEoB?= MUGyNlUyODV4MB?=
U2OS MXrGeY5kfGmxbjDBd5NigQ>? MUCxJOK2VQ>? NGjGV2szPCCq NEHP[3Ni[nKxZ3H0[ZMhd2ZiY3XscEBkgWOuZTDhdpJme3UEoB?= M3TncVIzPTFyNU[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:
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