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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2 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.

    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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Notes:

2. For more details, such as half maximal inhibitory concentrations (IC50s) and working concentrations of each inhibitor, please click on the link of the inhibitor of interest.
3. "+" indicates inhibitory effect. Increased inhibition is marked by a higher "+" designation.
4. Orange "√" refers to compounds which do inhibitory effects on the related isoform, but without specific value.

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)
Chk2 [1]
(Cell-free assay)
3 nM 0.16 μM 1.5 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 M1;rd2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NX3JT3dPOjByL{KwNFAhdk1? NHvkcJgzPCCq NEDGRoxl\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= NGjWbnUzPDN3OUWyOi=>
HCT115 NWXiOlY3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUjOOmdDOjByL{KwNFAhdk1? NFHFOYUzPCCq M{DR[YRm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= NF;DNHEzPDN3OUWyOi=>
SW620 NEHXcpVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4jLelIxOC9{MECwJI5O NFq0TVIzPCCq NF:0PXFl\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= MmDRNlQ{PTl3Mk[=
IGROV-1 M1G1W2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVTaT|l7OjByL{KwNFAhdk1? NGLZOXMzPCCq M4DXOIRm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= M3PnT|I1OzV7NUK2
HCT116 MkLPS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYSyNFAwOjByMDDuUS=> MYCyOEBp MXLk[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? MYqyOFM2QTV{Nh?=
MCF10A M1G5dWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIDz[3AzODBxMkCwNEBvVQ>? M37qXlI1KGh? Mm\t[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n MmnDNlQ{PTl3Mk[=
MiaPaCa-2 NEDpZ4VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWKyNFAwOjByMDDuUS=> NXXoNHdEOjRiaB?= M{XjOIRm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= NHztcXkzPDN3OUWyOi=>
MDA-MB-231 M2rCZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmezNlAxNzJyMECgcm0> NEDqS3QzPCCq MoL0[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n NFPxOY8zPDN3OUWyOi=>
HCC2998 NFfHO3VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3f3e|IxOC9{MECwJI5O MoPQNlQhcA>? NE\rOmxl\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= MUGyOFM2QTV{Nh?=
U87 NHjZU2tIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUPHeHNUOjByL{KwNFAhdk1? MVuyOEBp NFfZbJVl\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= MnH5NlQ{PTl3Mk[=
MDA-MB-435 M2fmVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXPM[49LOjByL{KwNFAhdk1? NIjzXXEzPCCq M4jZWoRm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= Mk\MNlQ{PTl3Mk[=
SNB19 MUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIDmc48zODBxMkCwNEBvVQ>? NXfNeGpJOjRiaB?= NYTSfWgx\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l NH7jRZUzPDN3OUWyOi=>
U20S NGL4XG9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGnF[5MzODBxMkCwNEBvVQ>? M37JflI1KGh? MkDU[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n NHS2RngzPDN3OUWyOi=>
A498 NYXSPWJ4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NX\NbWVlOjByL{KwNFAhdk1? MXGyOEBp MVjk[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? NHmxfoIzPDN3OUWyOi=>
TK10 NVzCTFlrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2\kVlIxOC9{MECwJI5O MV2yOEBp Mk\z[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n MoDrNlQ{PTl3Mk[=
AsPC-1 MoHQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFz0NWwzODBxMkCwNEBvVQ>? NGr0d|IzPCCq NXnhcW5r\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l MV:yOFM2QTV{Nh?=
H23 NInWXnJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoLDOVAxKG6P M{G2WlI1KGh? NH3LUJNFVVOR MkLX[Y5p[W6lZYOgeIhmKGOqZX3vd4Vve2m2aYrheIlwdiC2bzDQUXg> NGjpbY8zPDFzM{W0PS=>
H1437 NYrRNG11T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3PrRVUxOCCwTR?= NETw[5kzPCCq NY\uZoFrTE2VTx?= MnvV[Y5p[W6lZYOgeIhmKGOqZX3vd4Vve2m2aYrheIlwdiC2bzDQUXg> M3fVW|I1OTF|NUS5
H1993 MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NV;Mbm0xPTByIH7N NHL3fIYzPCCq MlnTSG1UVw>? M4DPe4VvcGGwY3XzJJRp\SClaHXtc5NmdnOrdHn6ZZRqd25idH:gVG1Z M4D6b|I1OTF|NUS5
H1299 NEDIb|RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXP0[Y9VPTByIH7N NUHZWlNsOjRiaB?= M3HXWWROW09? MUDlcohidmOnczD0bIUh[2inbX;z[Y5{cXSrenH0bY9vKHSxIGDNXC=> M3m2elI1OTF|NUS5
AsPC-1 NVrG[ppQT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVnXPFd1OTBvMUCwNEBvVQ>? NILkVoIzPC12OHi= M33KXYVvcGGwY3XzJJRp\SClaHXtc5NmdnOrdHn6ZZRqd25idH:g[4Vu[2m2YXLpcoU> M2\6blI{QDB2NEKy
MiaPaCa-2 M1vFOmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MV:xNE0yODByIH7N MWWyOE01QGh? NInZcXlmdmijbnPld{B1cGViY3jlcY9{\W6|aYTpfoF1cW:wIITvJIdmdWOrdHHibY5m MUWyN|gxPDR{Mh?=
BxPC-3 MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWG3VJE6OTBvMUCwNEBvVQ>? MUeyOE01QGh? MkTP[Y5p[W6lZYOgeIhmKGOqZX3vd4Vve2m2aYrheIlwdiC2bzDn[Y1kcXSjYnnu[S=> NWSyRYY2OjN6MES0NlI>
SKOV3 MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MljQNE4{KML3TR?= NUX5OIRtQCCm NYDWOXZ{e2Wwc3n0bZpmeyC2aHWgZ4VtdCCuaX7ld{B1dyCpZX3jbZRi[mmwZdMg NY\zclVTOjN3NEiyOlk>
OVCAR-8 NFL0eo1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIPLcngxNjNiwsXN NUO4OmlmQCCm NUfwdZlpe2Wwc3n0bZpmeyC2aHWgZ4VtdCCuaX7ld{B1dyCpZX3jbZRi[mmwZdMg MUKyN|U1QDJ4OR?=
MV-4-11 M1zGPWFxd3C2b4Ppd{BCe3OjeR?= MVyxNFAuPzByIH7N MVu0PEBp NXu1PY1rcW6mdXPld{BieG:ydH;zbZMh\G:|ZTDk[ZBmdmSnboTsfS=> NYK3PJo{OjN3M{[3NlE>
U937 MmPKRZBweHSxc3nzJGF{e2G7 MmLQNVAxNTdyMDDuUS=> MVW0PEBp NETSTmdqdmS3Y3XzJIFxd3C2b4Ppd{Bld3OnIHTldIVv\GWwdHz5 M3zoelI{PTN4N{Kx
MOLM-13  NGnPZWxCeG:ydH;zbZMhSXO|YYm= NFL2bZcyODBvN{CwJI5O NGTUUFE1QCCq MmSxbY5lfWOnczDhdI9xfG:|aYOg[I9{\SCmZYDlcoRmdnSueR?= NUPJTYxIOjN3M{[3NlE>
A2058  M3\nXmNmdGxiVnnhZoltcXS7IFHzd4F6 NH3FfXE{Py53LUOwNEBvVQ>? MoG2O|IhcA>? MX\EUXNQ NYPIOJRwemWmdXPld{B1cGViTVutNVc4PSCHQ{WwxsBjgSB3LX\vcIQhfG9iYX6gZZZmemGpZTDv[kA1PSCwTR?= NFHiSXMzOzF2OE[4OC=>
H2009 NVvQOnlIS2WubDDWbYFjcWyrdImgRZN{[Xl? MX21NFAhdk1? M3;mTlczKGh? NH;MbHFFVVOR MWfy[ZN2dHS|IHnuJGcyN1NvcHjhd4Uh[WOldX31cIF1cW:wIHPvcYJqdmWmIIfpeIghVUtvMUe3OS=> M1;i[VI{OTR6Nki0
Su.86.86 M1\HVmNmdGxiVnnhZoltcXS7IFHzd4F6 MWe1NFAhdk1? MoG5O|IhcA>? NY\jdXZ1TE2VTx?= Mn;DdoV{fWy2czDpckBIOS:VLYDoZZNmKGGlY4XteYxifGmxbjDjc41jcW6nZDD3bZRpKE2NLUG3O|U> M{DkOFI{OTR6Nki0
HRE MWLD[YxtKF[rYXLpcIl1gSCDc4PhfS=> MoDTOVAxKG6P NX\mZ5dxPzJiaB?= MoezSG1UVw>? MmLidoV{fWy2czDpckBIOS:VLYDoZZNmKGGlY4XteYxifGmxbjDjc41jcW6nZDD3bZRpKE2NLUG3O|U> NVLCc4Y5OjNzNEi2PFQ>
HMEC NVnJd5YzS2WubDDWbYFjcWyrdImgRZN{[Xl? MXW1NFAhdk1? NHizPWw4OiCq NUG0RYxoTE2VTx?= NHXETldz\XO3bITzJIlvKEdzL2OtdIhie2ViYXPjeY12dGG2aX;uJINwdWKrbnXkJJdqfGhiTVutNVc4PQ>? MnviNlMyPDh4OES=
U2OS  MnnTSpVv[3Srb36gRZN{[Xl? NIXEd44zKML3TR?= NGnWblExNTJ2IHi= MX;pcoR2[2W|IIDoc5NxcG:{eXzheIlwdiCxZjDDbIsyKGG2IIPldolv\SB|NEWgZZQh[m:2aDDjc45k\W62cnH0bY9veyCjczDlZZJtgSCjczCyJIgh[W[2ZYKgZYRucW6rc4TyZZRqd25? MnjNNlI6OzdzNEe=
U2OS  NGPmPW9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGH3eFkxNTFyINM1US=> NFe4RoczPC92ODDo NFS0UmJqdmirYnn0d{Bk\WyuIHfyc5d1cCCmb4PlJIRmeGWwZHXueIx6 MlXUNlI6OzdzNEe=
U937 MXrGeY5kfGmxbjDBd5NigQ>? MnrUNVAxNTVyMDDuUS=> MWm0JIjDqA>? MkjD[IVkemWjc3XzJJRp\SCleYThdoFjcW6nLXnu[JVk\WRiQ3jrNUBifXSxcHjvd5Bpd3K7bHH0bY9vKGG2IGPldlI6PsLiYX7kJJBz\X[nboTzJGNl[zJ3QTDkc5dvemWpdXzheIlwdg>? NWi4eIVJOjJ6Nkm4Olk>
U937 Ml;SSpVv[3Srb36gRZN{[Xl? MlP2NVAxKG6P M2LkSlQhcMLi M2HJXpJmfmW{c3XzJJRp\SCleYThdoFjcW6nLXnu[JVk\WRiaX7obYJqfGmxbjDv[uKhO0hvdHj5cYllcW6nIHnuZ49zeG:{YYTpc44hcW62bzDEUmE> M3XsflIzQDZ7OE[5
U937 NHP0bY9HfW6ldHnvckBCe3OjeR?= MXqxNFAuPTByIH7N NE\tR2Y1KGkEoB?= M3\Ge4lv\HWlZYOgbY5kemWjc3XkJJBpd3OyaH;yfYxifGmxbjDv[kBJOkG[ NHLT[oEzOjh4OUi2PS=>
HL-60 MWHBdI9xfG:|aYOgRZN{[Xl? MW[zNE8yODBxM{CwJI5O NHK1VHIzPCCq MkXzSG1UVw>? NFfFfI9mdmijbnPld{BkgXSjcnHibY5mNWmwZIXj[YQh[XCxcITvd4l{ NGTo[mEzOjh4OUi2PS=>
ML-1 Mn3YRZBweHSxc3nzJGF{e2G7 M4rYOlI2NzVyL{GwNEBvVQ>? M13sWlI1KGh? MofnSG1UVw>? MlHh[Y5p[W6lZYOgZ5l1[XKjYnnu[U1qdmS3Y3XkJIFxd3C2b4Ppdy=> NVfMbY5yOjJ6Nkm4Olk>
HCT116 NGPsWmJHfW6ldHnvckBCe3OjeR?= MUixJOK2VQ>? NFrFepQzPCCq NHHqS4Ji[nKxZ3H0[ZMhd2ZiY3XscEBkgWOuZTDhdpJme3UEoB?= M4n4e|IzPTFyNU[w
U2OS MlzaSpVv[3Srb36gRZN{[Xl? NXLtRlYxOSEEtV2= MX2yOEBp MWXhZpJw\2G2ZYOgc4Yh[2WubDDjfYNt\SCjcoLld5TDqA>? NHry[ngzOjVzMEW2NC=>

... 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
+ 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 <1 mg/mL
Ethanol <1 mg/mL
In vivo 4% DMSO+30% propylene glycol 5 mg/mL

* 1 mg/ml means slightly soluble or insoluble.
* 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
NCT01870596 Active, not recruiting 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