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 Mn\PS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUHBbGF1OjByL{KwNFAhdk1? M1WwU|I1KGh? MVfk[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? M4LFO|I1OzV7NUK2
HCT115 MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVzFTolQOjByL{KwNFAhdk1? MlvYNlQhcA>? MoXq[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n M3ntTVI1OzV7NUK2
SW620 M4HZXmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmCxNlAxNzJyMECgcm0> Mkj0NlQhcA>? MW\k[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? NIP4SZYzPDN3OUWyOi=>
IGROV-1 MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{jxelIxOC9{MECwJI5O MYOyOEBp NUjqeoM{\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l MUSyOFM2QTV{Nh?=
HCT116 M1jzRmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWjxRWN{OjByL{KwNFAhdk1? Ml\INlQhcA>? MkTk[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n MnrONlQ{PTl3Mk[=
MCF10A MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFfDNmMzODBxMkCwNEBvVQ>? NHzlbZUzPCCq MVvk[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? NGrl[48zPDN3OUWyOi=>
MiaPaCa-2 NYDXOGpmT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkHZNlAxNzJyMECgcm0> NX7CXpl6OjRiaB?= M1nNXYRm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= NVfLT5REOjR|NUm1NlY>
MDA-MB-231 M3G4UWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Ml3XNlAxNzJyMECgcm0> NYi0SYhuOjRiaB?= M3LYbIRm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= NFfCRZEzPDN3OUWyOi=>
HCC2998 MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEjofI8zODBxMkCwNEBvVQ>? M2rHfFI1KGh? MX7k[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? NGDFc|AzPDN3OUWyOi=>
U87 NHi3fnZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVztfIs3OjByL{KwNFAhdk1? NGTROoMzPCCq MnjI[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n NWfuOndMOjR|NUm1NlY>
MDA-MB-435 M170d2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnznNlAxNzJyMECgcm0> NGfvcYEzPCCq Mn\L[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n NETRbnYzPDN3OUWyOi=>
SNB19 M2nyfGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXPwZWFJOjByL{KwNFAhdk1? M3PMdFI1KGh? MWTk[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? MWmyOFM2QTV{Nh?=
U20S NEjZPXBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVPiboNTOjByL{KwNFAhdk1? MnXJNlQhcA>? MV;k[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? M4HjO|I1OzV7NUK2
A498 Mln3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIT2ZZgzODBxMkCwNEBvVQ>? M{Pub|I1KGh? MkPR[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n NFWzPYEzPDN3OUWyOi=>
TK10 NVn4b3NYT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4D4U|IxOC9{MECwJI5O NFPue4QzPCCq NF3sfoNl\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= MlPyNlQ{PTl3Mk[=
AsPC-1 NYLYRZBoT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWSyNFAwOjByMDDuUS=> MV:yOEBp M{nWSoRm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= MknhNlQ{PTl3Mk[=
H23 MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{W2[FUxOCCwTR?= MmLtNlQhcA>? NGLPfGdFVVOR NUDZWIVM\W6qYX7j[ZMhfGinIHPo[Y1we2Wwc3n0bZpifGmxbjD0c{BRVVh? Mme4NlQyOTN3NEm=
H1437 MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NV;SUXV3PTByIH7N NWfqeY5wOjRiaB?= MVHEUXNQ MUHlcohidmOnczD0bIUh[2inbX;z[Y5{cXSrenH0bY9vKHSxIGDNXC=> MmTUNlQyOTN3NEm=
H1993 M2XLXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVr3bGNDPTByIH7N MkfxNlQhcA>? NETPZlVFVVOR NX\CZlRk\W6qYX7j[ZMhfGinIHPo[Y1we2Wwc3n0bZpifGmxbjD0c{BRVVh? M1fYU|I1OTF|NUS5
H1299 NYDMOpdGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVHiV5hrPTByIH7N M3;SfVI1KGh? M4rrWGROW09? Ml;r[Y5p[W6lZYOgeIhmKGOqZX3vd4Vve2m2aYrheIlwdiC2bzDQUXg> MYSyOFEyOzV2OR?=
AsPC-1 M3;lSWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnzmNVAuOTByMDDuUS=> NWHCdYZXOjRvNEjo MUnlcohidmOnczD0bIUh[2inbX;z[Y5{cXSrenH0bY9vKHSxIHflcYNqfGGkaX7l NIrlOJIzOzhyNESyNi=>
MiaPaCa-2 NYnhOY53T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUXPR4Q4OTBvMUCwNEBvVQ>? MmPCNlQuPDiq MVrlcohidmOnczD0bIUh[2inbX;z[Y5{cXSrenH0bY9vKHSxIHflcYNqfGGkaX7l Ml3xNlM5ODR2MkK=
BxPC-3 MkXrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NX7iSpF{OTBvMUCwNEBvVQ>? NUjkfJNWOjRvNEjo MULlcohidmOnczD0bIUh[2inbX;z[Y5{cXSrenH0bY9vKHSxIHflcYNqfGGkaX7l MViyN|gxPDR{Mh?=
SKOV3 M2jTfmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1rXPVAvOyEEtV2= MXq4JIQ> MWPz[Y5{cXSrenXzJJRp\SClZXzsJIxqdmW|IITvJIdmdWOrdHHibY5myqB? NXnCRnQxOjN3NEiyOlk>
OVCAR-8 MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlLENE4{KML3TR?= NYLTc4V{QCCm MljJd4Vve2m2aYrld{B1cGViY3XscEBtcW6nczD0c{Bo\W2laYThZolv\cLi MkPvNlM2PDh{Nkm=
MV-4-11 MoPLRZBweHSxc3nzJGF{e2G7 MmGwNVAxNTdyMDDuUS=> M1\VcVQ5KGh? M{[1S4lv\HWlZYOgZZBweHSxc3nzJIRwe2ViZHXw[Y5l\W62bIm= NELxbXEzOzV|NkeyNS=>
U937 NVrCeWt5SXCxcITvd4l{KEG|c3H5 MkTZNVAxNTdyMDDuUS=> M2n3e|Q5KGh? M4r4ZYlv\HWlZYOgZZBweHSxc3nzJIRwe2ViZHXw[Y5l\W62bIm= MV:yN|U{Pjd{MR?=
MOLM-13  NYnx[HdKSXCxcITvd4l{KEG|c3H5 NWLrUpM{OTByLUewNEBvVQ>? M2\LflQ5KGh? MW\pcoR2[2W|IHHwc5B1d3OrczDkc5NmKGSncHXu[IVvfGy7 NFTaSZAzOzV|NkeyNS=>
A2058  NEW0N|lE\WyuIG\pZYJqdGm2eTDBd5NigQ>? NHKyWI4{Py53LUOwNEBvVQ>? MWi3NkBp MofsSG1UVw>? MUPy[YR2[2W|IITo[UBOUy1zN{e1JGVEPTEEoHL5JFUu\m:uZDD0c{BidiCjdnXyZYdmKG:oIES1JI5O MUCyN|E1QDZ6NB?=
H2009 NEHSOo1E\WyuIG\pZYJqdGm2eTDBd5NigQ>? M1\t[VUxOCCwTR?= M{XXfVczKGh? MlTKSG1UVw>? M3nDepJme3WudIOgbY4hTzFxUz3wbIF{\SCjY3P1cZVt[XSrb36gZ49u[mmwZXSge4l1cCCPSz2xO|c2 NHXk[lgzOzF2OE[4OC=>
Su.86.86 MXHD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NGj4Spo2ODBibl2= NHrBTJA4OiCq MmH0SG1UVw>? M1rFZZJme3WudIOgbY4hTzFxUz3wbIF{\SCjY3P1cZVt[XSrb36gZ49u[mmwZXSge4l1cCCPSz2xO|c2 NVrHd|lkOjNzNEi2PFQ>
HRE M3L6VGNmdGxiVnnhZoltcXS7IFHzd4F6 MXi1NFAhdk1? MY[3NkBp MUXEUXNQ Mn36doV{fWy2czDpckBIOS:VLYDoZZNmKGGlY4XteYxifGmxbjDjc41jcW6nZDD3bZRpKE2NLUG3O|U> MlviNlMyPDh4OES=
HMEC M2TYdWNmdGxiVnnhZoltcXS7IFHzd4F6 M2jRWlUxOCCwTR?= MmLkO|IhcA>? M3\PXGROW09? NX7CRpF{emW|dXz0d{BqdiCJMT;TMZBp[XOnIHHjZ5VufWyjdHnvckBkd22kaX7l[EB4cXSqIF3LMVE4PzV? NY\FUo9iOjNzNEi2PFQ>
U2OS  Mme5SpVv[3Srb36gRZN{[Xl? NV[zNZpROiEEtV2= MYCwMVI1KGh? NVvZbGI4cW6mdXPld{BxcG:|cHjvdplt[XSrb36gc4YhS2itMTDheEB{\XKrbnWgN|Q2KGG2IHLveIgh[2:wY3XueJJifGmxboOgZZMh\WG{bImgZZMhOiCqIHHmeIVzKGGmbXnubZN1emG2aX;u NHLlVpIzOjl|N{G0Oy=>
U2OS  M{TR[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NE[2XFQxNTFyINM1US=> M1vhUFI1NzR6IHi= MnvibY5pcWKrdIOgZ4VtdCCpcn;3eIgh\G:|ZTDk[ZBmdmSnboTsfS=> NITKe5czOjl|N{G0Oy=>
U937 MmG3SpVv[3Srb36gRZN{[Xl? M3jCflExOC13MECgcm0> MXS0JIjDqA>? NIDYdXll\WO{ZXHz[ZMhfGinIHP5eIFz[WKrbnWtbY5lfWOnZDDDbIsyKGG3dH;wbI9{eGixconsZZRqd25iYYSgV4VzOjl4wrDhcoQheHKndnXueJMhS2SlMkXBJIRwf26{ZXf1cIF1cW:w M1n1cFIzQDZ7OE[5
U937 MY\GeY5kfGmxbjDBd5NigQ>? NIPmWZQyODBibl2= NVjKcJh6PCCqwrC= NIr4bY5z\X[ncoPld{B1cGViY4n0ZZJi[mmwZT3pcoR2[2WmIHnubIljcXSrb36gc4bDqDOKLYTofY1q\GmwZTDpcoNwenCxcnH0bY9vKGmwdH:gSG5C M1e1TlIzQDZ7OE[5
U937 NWrzU2s6TnWwY4Tpc44hSXO|YYm= NUC1SVhuOTByLUWwNEBvVQ>? NHLRNGg1KGkEoB?= NV7BXZo6cW6mdXPld{BqdmO{ZXHz[YQheGixc4Doc5J6dGG2aX;uJI9nKEh{QWi= NITjW2kzOjh4OUi2PS=>
HL-60 NX7JemNOSXCxcITvd4l{KEG|c3H5 NY\DcJhnOzBxMUCwM|MxOCCwTR?= M1TmZ|I1KGh? M1j5UGROW09? MmjL[Y5p[W6lZYOgZ5l1[XKjYnnu[U1qdmS3Y3XkJIFxd3C2b4Ppdy=> NUfnXYRzOjJ6Nkm4Olk>
ML-1 M4XldWFxd3C2b4Ppd{BCe3OjeR?= NWLMZZpJOjVxNUCvNVAxKG6P NYPz[XJiOjRiaB?= MlziSG1UVw>? M1fyNIVvcGGwY3XzJIN6fGG{YXLpcoUucW6mdXPl[EBieG:ydH;zbZM> MWmyNlg3QTh4OR?=
HCT116 MVrGeY5kfGmxbjDBd5NigQ>? MkO1NUDDvU1? Mnj0NlQhcA>? NHK2UlZi[nKxZ3H0[ZMhd2ZiY3XscEBkgWOuZTDhdpJme3UEoB?= M1nuVFIzPTFyNU[w
U2OS NX;2WHNHTnWwY4Tpc44hSXO|YYm= NYr3enI2OSEEtV2= Ml3uNlQhcA>? NXrwc2d4[WK{b3fheIV{KG:oIHPlcIwh[3mlbHWgZZJz\XO2wrC= M4XV[lIzPTFyNU[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 <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 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

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID