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 MnvHS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2TwclIxOC9{MECwJI5O MYOyOEBp NETaTJJl\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= NFHlS3AzPDN3OUWyOi=>
HCT115 NGXZNnFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmqzNlAxNzJyMECgcm0> NW\2Z3VrOjRiaB?= M1HubIRm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= MV2yOFM2QTV{Nh?=
SW620 MkH1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mk\MNlAxNzJyMECgcm0> NH3XR3QzPCCq NH;kcpBl\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= M1uxSVI1OzV7NUK2
IGROV-1 MlnrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVfEWXJ3OjByL{KwNFAhdk1? MoPSNlQhcA>? M4nXT4Rm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= NUX2UZZWOjR|NUm1NlY>
HCT116 MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVjQfGE5OjByL{KwNFAhdk1? MnH5NlQhcA>? MlLz[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n NYXSdFFzOjR|NUm1NlY>
MCF10A Ml\DS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1;QV|IxOC9{MECwJI5O Ml3kNlQhcA>? NVrKNot[\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l MoTJNlQ{PTl3Mk[=
MiaPaCa-2 MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3ziUVIxOC9{MECwJI5O MUiyOEBp M3rH[YRm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= MmLtNlQ{PTl3Mk[=
MDA-MB-231 NWXiWnlGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NF;IXVMzODBxMkCwNEBvVQ>? Mln0NlQhcA>? MmX6[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n M{D0c|I1OzV7NUK2
HCC2998 MnLxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYCyNFAwOjByMDDuUS=> MYGyOEBp Mmr1[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n NX74foxXOjR|NUm1NlY>
U87 MkPsS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnHKNlAxNzJyMECgcm0> NGLhWFkzPCCq M2DkWYRm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= NILWd2ozPDN3OUWyOi=>
MDA-MB-435 MkHyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Ml2wNlAxNzJyMECgcm0> NXPtTWxMOjRiaB?= MX;k[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? NUXDPGd2OjR|NUm1NlY>
SNB19 MoTpS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mn64NlAxNzJyMECgcm0> MXeyOEBp NULx[48z\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l M17YfVI1OzV7NUK2
U20S NW[1XG56T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoDkNlAxNzJyMECgcm0> MkTXNlQhcA>? M4nsUoRm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= MWmyOFM2QTV{Nh?=
A498 NW\we5RxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIj6ZWkzODBxMkCwNEBvVQ>? NVrOS|NZOjRiaB?= M4PMbYRm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= MUiyOFM2QTV{Nh?=
TK10 M1;oTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Moj2NlAxNzJyMECgcm0> NV2xRphLOjRiaB?= NUfYU3FC\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l NUnRV2ZqOjR|NUm1NlY>
AsPC-1 NGPHbJhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYOyNFAwOjByMDDuUS=> M1vEeVI1KGh? NITsc21l\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= NIHzXHIzPDN3OUWyOi=>
H23 MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHXhUY02ODBibl2= MkHrNlQhcA>? MofWSG1UVw>? NV;XZnht\W6qYX7j[ZMhfGinIHPo[Y1we2Wwc3n0bZpifGmxbjD0c{BRVVh? NXPOWYNEOjRzMUO1OFk>
H1437 M33JZmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{K4WFUxOCCwTR?= NVfzUFhmOjRiaB?= MWfEUXNQ NIXQUHFmdmijbnPld{B1cGViY3jlcY9{\W6|aYTpfoF1cW:wIITvJHBOYA>? Mne1NlQyOTN3NEm=
H1993 M2P0OGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEXlPXY2ODBibl2= NVTsXZM3OjRiaB?= NUDESnlxTE2VTx?= NIrMPGlmdmijbnPld{B1cGViY3jlcY9{\W6|aYTpfoF1cW:wIITvJHBOYA>? MVWyOFEyOzV2OR?=
H1299 MYLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M322SFUxOCCwTR?= MnvsNlQhcA>? MXLEUXNQ MWjlcohidmOnczD0bIUh[2inbX;z[Y5{cXSrenH0bY9vKHSxIGDNXC=> M4DudVI1OTF|NUS5
AsPC-1 M2jYc2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHi5S3kyOC1zMECwJI5O MnToNlQuPDiq MV7lcohidmOnczD0bIUh[2inbX;z[Y5{cXSrenH0bY9vKHSxIHflcYNqfGGkaX7l NF;NU2QzOzhyNESyNi=>
MiaPaCa-2 MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2G1U|ExNTFyMECgcm0> MlL1NlQuPDiq M123[YVvcGGwY3XzJJRp\SClaHXtc5NmdnOrdHn6ZZRqd25idH:g[4Vu[2m2YXLpcoU> NUXnWmJPOjN6MES0NlI>
BxPC-3 MYLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWKxNE0yODByIH7N M2T5UFI1NTR6aB?= NYP0elFt\W6qYX7j[ZMhfGinIHPo[Y1we2Wwc3n0bZpifGmxbjD0c{Bo\W2laYThZolv\Q>? M4TseFI{QDB2NEKy
SKOV3 NXSybVh5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MX6wMlMhyrWP MWS4JIQ> MWHz[Y5{cXSrenXzJJRp\SClZXzsJIxqdmW|IITvJIdmdWOrdHHibY5myqB? NF:4NoYzOzV2OEK2PS=>
OVCAR-8 NHPQW2RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHfyWJIxNjNiwsXN M2\neFgh\A>? MoXZd4Vve2m2aYrld{B1cGViY3XscEBtcW6nczD0c{Bo\W2laYThZolv\cLi M{ToclI{PTR6Mk[5
MV-4-11 NUnyblFSSXCxcITvd4l{KEG|c3H5 MXSxNFAuPzByIH7N MlfyOFghcA>? NVrFbnlTcW6mdXPld{BieG:ydH;zbZMh\G:|ZTDk[ZBmdmSnboTsfS=> M3HDe|I{PTN4N{Kx
U937 MXjBdI9xfG:|aYOgRZN{[Xl? NXjnXFd[OTByLUewNEBvVQ>? NU\yd41PPDhiaB?= MV3pcoR2[2W|IHHwc5B1d3OrczDkc5NmKGSncHXu[IVvfGy7 NH\UXJEzOzV|NkeyNS=>
MOLM-13  MXrBdI9xfG:|aYOgRZN{[Xl? NXrFWJZxOTByLUewNEBvVQ>? NVi4XpYxPDhiaB?= NUPMbG13cW6mdXPld{BieG:ydH;zbZMh\G:|ZTDk[ZBmdmSnboTsfS=> NVP6fmQ3OjN3M{[3NlE>
A2058  NVnreWFUS2WubDDWbYFjcWyrdImgRZN{[Xl? MVezO{42NTNyMDDuUS=> MWK3NkBp MVnEUXNQ M2jIW5Jm\HWlZYOgeIhmKE2NLUG3O|UhTUN3MNMgZpkhPS2ob3zkJJRwKGGwIHH2[ZJi\2Vib3[gOFUhdk1? NFnzNGgzOzF2OE[4OC=>
H2009 M2ToWmNmdGxiVnnhZoltcXS7IFHzd4F6 M3TNNlUxOCCwTR?= NVfXOIQ5PzJiaB?= M3;WZ2ROW09? NYHRTndremW|dXz0d{BqdiCJMT;TMZBp[XOnIHHjZ5VufWyjdHnvckBkd22kaX7l[EB4cXSqIF3LMVE4PzV? NFTBN4gzOzF2OE[4OC=>
Su.86.86 M4exXGNmdGxiVnnhZoltcXS7IFHzd4F6 NX\WN4VsPTByIH7N MY[3NkBp MoXGSG1UVw>? M3rQ[pJme3WudIOgbY4hTzFxUz3wbIF{\SCjY3P1cZVt[XSrb36gZ49u[mmwZXSge4l1cCCPSz2xO|c2 Mny4NlMyPDh4OES=
HRE NXTZRYpMS2WubDDWbYFjcWyrdImgRZN{[Xl? NYexWmZDPTByIH7N NX74O3F2PzJiaB?= MoXpSG1UVw>? NHuxWJlz\XO3bITzJIlvKEdzL2OtdIhie2ViYXPjeY12dGG2aX;uJINwdWKrbnXkJJdqfGhiTVutNVc4PQ>? NX2xTpdwOjNzNEi2PFQ>
HMEC M4TWV2NmdGxiVnnhZoltcXS7IFHzd4F6 NI\sPXo2ODBibl2= NXzVclhsPzJiaB?= NI\rNmVFVVOR M2HYRZJme3WudIOgbY4hTzFxUz3wbIF{\SCjY3P1cZVt[XSrb36gZ49u[mmwZXSge4l1cCCPSz2xO|c2 MYiyN|E1QDZ6NB?=
U2OS  NYTYZXVxTnWwY4Tpc44hSXO|YYm= NVXwRoc3OiEEtV2= MlTCNE0zPCCq NYrIcHQ5cW6mdXPld{BxcG:|cHjvdplt[XSrb36gc4YhS2itMTDheEB{\XKrbnWgN|Q2KGG2IHLveIgh[2:wY3XueJJifGmxboOgZZMh\WG{bImgZZMhOiCqIHHmeIVzKGGmbXnubZN1emG2aX;u NVrUbHo2OjJ7M{exOFc>
U2OS  MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmruNE0yOCEEtV2= MVmyOE81QCCq NXjPb2M6cW6qaXLpeJMh[2WubDDndo94fGhiZH;z[UBl\XCnbnTlcpRtgQ>? NFXZbJUzOjl|N{G0Oy=>
U937 MmHiSpVv[3Srb36gRZN{[Xl? NX;I[WdKOTByLUWwNEBvVQ>? Mor4OEBpyqB? NUPKZYlb\GWlcnXhd4V{KHSqZTDjfZRiemGkaX7lMYlv\HWlZXSgR4hsOSCjdYTvdIhwe3Cqb4L5cIF1cW:wIHH0JHNmejJ7NtMgZY5lKHC{ZY\lcpR{KEOmY{K1RUBld3ewcnXneYxifGmxbh?= MmLlNlI5Pjl6Nkm=
U937 M{LOSWZ2dmO2aX;uJGF{e2G7 MofKNVAxKG6P NVH6XIRHPCCqwrC= NUnXUFVDemW4ZYLz[ZMhfGinIHP5eIFz[WKrbnWtbY5lfWOnZDDpcohq[mm2aX;uJI9nyqB|SD30bJlucWSrbnWgbY5kd3Kyb4LheIlwdiCrboTvJGRPSQ>? M2PYdlIzQDZ7OE[5
U937 MmTFSpVv[3Srb36gRZN{[Xl? MVmxNFAuPTByIH7N MmrROEBpyqB? M1nrUolv\HWlZYOgbY5kemWjc3XkJJBpd3OyaH;yfYxifGmxbjDv[kBJOkG[ NVrNO4kyOjJ6Nkm4Olk>
HL-60 M1z2PWFxd3C2b4Ppd{BCe3OjeR?= MU[zNE8yODBxM{CwJI5O MWWyOEBp MW\EUXNQ NXHGRYdZ\W6qYX7j[ZMh[3m2YYLhZolv\S2rbnT1Z4VlKGGyb4D0c5Nqew>? MVGyNlg3QTh4OR?=
ML-1 NVL4VodGSXCxcITvd4l{KEG|c3H5 M1nBfVI2NzVyL{GwNEBvVQ>? NE[2cmwzPCCq NFvpVVlFVVOR NIi2bmhmdmijbnPld{BkgXSjcnHibY5mNWmwZIXj[YQh[XCxcITvd4l{ NXvVRpV7OjJ6Nkm4Olk>
HCT116 MX;GeY5kfGmxbjDBd5NigQ>? MnniNUDDvU1? NHK5VmwzPCCq MljpZYJzd2ejdHXzJI9nKGOnbHygZ5lkdGViYYLy[ZN1yqB? NHPreo4zOjVzMEW2NC=>
U2OS MkfhSpVv[3Srb36gRZN{[Xl? MUOxJOK2VQ>? NVW3N5V5OjRiaB?= NF7nNYVi[nKxZ3H0[ZMhd2ZiY3XscEBkgWOuZTDhdpJme3UEoB?= MYqyNlUyODV4MB?=

... 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