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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3 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.

  • 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 MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnXrNlAxNzJyMECgcm0> M2TBTFI1KGh? Mnz2[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n NILjToczPDN3OUWyOi=>
HCT115 MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkfWNlAxNzJyMECgcm0> NUf6TY1GOjRiaB?= NYDC[ItO\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l NFLOeXQzPDN3OUWyOi=>
SW620 NHrDcFBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYfXO3JGOjByL{KwNFAhdk1? NFuzW|AzPCCq NIrr[nBl\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= Ml;3NlQ{PTl3Mk[=
IGROV-1 M2nS[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4WwT|IxOC9{MECwJI5O MWOyOEBp Mknq[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n NGnFeIwzPDN3OUWyOi=>
HCT116 NETjd|lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlTtNlAxNzJyMECgcm0> M1P4W|I1KGh? MXXk[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? M1y5ZVI1OzV7NUK2
MCF10A MlzlS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3XWflIxOC9{MECwJI5O M3nR[lI1KGh? MX3k[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? NGnQeYozPDN3OUWyOi=>
MiaPaCa-2 M1vMdmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYnYWplpOjByL{KwNFAhdk1? M4fGWlI1KGh? Mork[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n NHq1UJMzPDN3OUWyOi=>
MDA-MB-231 MoiyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M13ZclIxOC9{MECwJI5O M3\KOVI1KGh? MonX[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n NEf3ZmIzPDN3OUWyOi=>
HCC2998 M1WxO2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYKyNFAwOjByMDDuUS=> M{XKXlI1KGh? Ml60[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n MoPzNlQ{PTl3Mk[=
U87 MkjqS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVKyNFAwOjByMDDuUS=> MoH5NlQhcA>? NH3ZVGRl\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= Mon1NlQ{PTl3Mk[=
MDA-MB-435 MknuS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NX;VTFJqOjByL{KwNFAhdk1? M161WVI1KGh? NVTwWG5i\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l MX[yOFM2QTV{Nh?=
SNB19 MlHkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoqzNlAxNzJyMECgcm0> MkPiNlQhcA>? NUfaXo57\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l M1PpVFI1OzV7NUK2
U20S MojJS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NX\Rdo9[OjByL{KwNFAhdk1? M4\1VVI1KGh? M{fM[4Rm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= MW[yOFM2QTV{Nh?=
A498 MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIq2UFUzODBxMkCwNEBvVQ>? M4fDOlI1KGh? Mlnm[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n MWGyOFM2QTV{Nh?=
TK10 MmTaS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlvCNlAxNzJyMECgcm0> M1;4SVI1KGh? M2fFToRm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= NVf1SVhIOjR|NUm1NlY>
AsPC-1 Mo\DS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2PIelIxOC9{MECwJI5O M2rsVlI1KGh? NVPtd4c2\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l NUDWb3ltOjR|NUm1NlY>
H23 MlfpS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXS1NFAhdk1? M3yzR|I1KGh? M3;YSGROW09? MVPlcohidmOnczD0bIUh[2inbX;z[Y5{cXSrenH0bY9vKHSxIGDNXC=> MVKyOFEyOzV2OR?=
H1437 MlPOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUG1NFAhdk1? MoTlNlQhcA>? M1LBWmROW09? NUXIWVZ6\W6qYX7j[ZMhfGinIHPo[Y1we2Wwc3n0bZpifGmxbjD0c{BRVVh? NHPiNnQzPDFzM{W0PS=>
H1993 M4\5bWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFvVd3k2ODBibl2= NV\zOlg4OjRiaB?= MW\EUXNQ Mk\E[Y5p[W6lZYOgeIhmKGOqZX3vd4Vve2m2aYrheIlwdiC2bzDQUXg> MmPlNlQyOTN3NEm=
H1299 NHTXfo9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHTReHM2ODBibl2= NHrmdI8zPCCq NILyVppFVVOR MnHL[Y5p[W6lZYOgeIhmKGOqZX3vd4Vve2m2aYrheIlwdiC2bzDQUXg> NVXXW2hCOjRzMUO1OFk>
AsPC-1 MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NE\qN3QyOC1zMECwJI5O MXqyOE01QGh? NGjGOGdmdmijbnPld{B1cGViY3jlcY9{\W6|aYTpfoF1cW:wIITvJIdmdWOrdHHibY5m MWmyN|gxPDR{Mh?=
MiaPaCa-2 NFvyVotIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Ml6wNVAuOTByMDDuUS=> M1vWblI1NTR6aB?= NIDBfGdmdmijbnPld{B1cGViY3jlcY9{\W6|aYTpfoF1cW:wIITvJIdmdWOrdHHibY5m Ml2zNlM5ODR2MkK=
BxPC-3 MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXzaUnRlOTBvMUCwNEBvVQ>? MnnxNlQuPDiq NWTJUo96\W6qYX7j[ZMhfGinIHPo[Y1we2Wwc3n0bZpifGmxbjD0c{Bo\W2laYThZolv\Q>? M17MR|I{QDB2NEKy
SKOV3 NY\RWYZzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2G2d|AvOyEEtV2= MU[4JIQ> MX7z[Y5{cXSrenXzJJRp\SClZXzsJIxqdmW|IITvJIdmdWOrdHHibY5myqB? NYfWUnFDOjN3NEiyOlk>
OVCAR-8 NXnie2xvT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWfOOYhoOC5|INM1US=> M33RbFgh\A>? MoLUd4Vve2m2aYrld{B1cGViY3XscEBtcW6nczD0c{Bo\W2laYThZolv\cLi M1TFV|I{PTR6Mk[5
MV-4-11 M{HVV2Fxd3C2b4Ppd{BCe3OjeR?= M3rYXFExOC15MECgcm0> NIjxd3U1QCCq M1TxNIlv\HWlZYOgZZBweHSxc3nzJIRwe2ViZHXw[Y5l\W62bIm= NWXvToFSOjN3M{[3NlE>
U937 MoHxRZBweHSxc3nzJGF{e2G7 NF3TN5gyODBvN{CwJI5O MV:0PEBp NWjzO4JZcW6mdXPld{BieG:ydH;zbZMh\G:|ZTDk[ZBmdmSnboTsfS=> M1jpclI{PTN4N{Kx
MOLM-13  NWrWfYY{SXCxcITvd4l{KEG|c3H5 MVGxNFAuPzByIH7N MUi0PEBp MULpcoR2[2W|IHHwc5B1d3OrczDkc5NmKGSncHXu[IVvfGy7 MUWyN|U{Pjd{MR?=
A2058  MV;D[YxtKF[rYXLpcIl1gSCDc4PhfS=> MkjiN|cvPS1|MECgcm0> M{jJZlczKGh? NX3PcWZFTE2VTx?= M4PLXZJm\HWlZYOgeIhmKE2NLUG3O|UhTUN3MNMgZpkhPS2ob3zkJJRwKGGwIHH2[ZJi\2Vib3[gOFUhdk1? NIjGcZUzOzF2OE[4OC=>
H2009 M2\yWmNmdGxiVnnhZoltcXS7IFHzd4F6 M4jQSlUxOCCwTR?= NFPJco84OiCq M1\QS2ROW09? NFXCfHpz\XO3bITzJIlvKEdzL2OtdIhie2ViYXPjeY12dGG2aX;uJINwdWKrbnXkJJdqfGhiTVutNVc4PQ>? M124SVI{OTR6Nki0
Su.86.86 M1;UcGNmdGxiVnnhZoltcXS7IFHzd4F6 MmfFOVAxKG6P MYO3NkBp M1HsV2ROW09? MmjqdoV{fWy2czDpckBIOS:VLYDoZZNmKGGlY4XteYxifGmxbjDjc41jcW6nZDD3bZRpKE2NLUG3O|U> NFHr[3czOzF2OE[4OC=>
HRE NVXHS4dIS2WubDDWbYFjcWyrdImgRZN{[Xl? MXK1NFAhdk1? Mn:xO|IhcA>? MVzEUXNQ MYXy[ZN2dHS|IHnuJGcyN1NvcHjhd4Uh[WOldX31cIF1cW:wIHPvcYJqdmWmIIfpeIghVUtvMUe3OS=> M1vJcFI{OTR6Nki0
HMEC NIrSV5NE\WyuIG\pZYJqdGm2eTDBd5NigQ>? M3zGO|UxOCCwTR?= MVO3NkBp MXzEUXNQ MWfy[ZN2dHS|IHnuJGcyN1NvcHjhd4Uh[WOldX31cIF1cW:wIHPvcYJqdmWmIIfpeIghVUtvMUe3OS=> NG\idIczOzF2OE[4OC=>
U2OS  NF7lT4lHfW6ldHnvckBCe3OjeR?= NF7sW5UzKML3TR?= MXiwMVI1KGh? NUXtWYtWcW6mdXPld{BxcG:|cHjvdplt[XSrb36gc4YhS2itMTDheEB{\XKrbnWgN|Q2KGG2IHLveIgh[2:wY3XueJJifGmxboOgZZMh\WG{bImgZZMhOiCqIHHmeIVzKGGmbXnubZN1emG2aX;u NWH2dmJWOjJ7M{exOFc>
U2OS  M{TITmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{XIVVAuOTBiwsXN MVuyOE81QCCq MlSxbY5pcWKrdIOgZ4VtdCCpcn;3eIgh\G:|ZTDk[ZBmdmSnboTsfS=> MVWyNlk{PzF2Nx?=
U937 M4X0[2Z2dmO2aX;uJGF{e2G7 NGnnbmoyODBvNUCwJI5O NEPtXHQ1KGkEoB?= NGWxZ3Zl\WO{ZXHz[ZMhfGinIHP5eIFz[WKrbnWtbY5lfWOnZDDDbIsyKGG3dH;wbI9{eGixconsZZRqd25iYYSgV4VzOjl4wrDhcoQheHKndnXueJMhS2SlMkXBJIRwf26{ZXf1cIF1cW:w MV6yNlg3QTh4OR?=
U937 MmXiSpVv[3Srb36gRZN{[Xl? M1PURVExOCCwTR?= MkT5OEBpyqB? M4rFUpJmfmW{c3XzJJRp\SCleYThdoFjcW6nLXnu[JVk\WRiaX7obYJqfGmxbjDv[uKhO0hvdHj5cYllcW6nIHnuZ49zeG:{YYTpc44hcW62bzDEUmE> M4nTRVIzQDZ7OE[5
U937 MVTGeY5kfGmxbjDBd5NigQ>? MYGxNFAuPTByIH7N NETOV4U1KGkEoB?= MYPpcoR2[2W|IHnuZ5Jm[XOnZDDwbI9{eGixconsZZRqd25ib3[gTFJCYA>? Ml\TNlI5Pjl6Nkm=
HL-60 NVTLfll5SXCxcITvd4l{KEG|c3H5 MWqzNE8yODBxM{CwJI5O NXXJWXh2OjRiaB?= NVzJbm5mTE2VTx?= NUH3WmZW\W6qYX7j[ZMh[3m2YYLhZolv\S2rbnT1Z4VlKGGyb4D0c5Nqew>? NYLQeW11OjJ6Nkm4Olk>
ML-1 M3W3d2Fxd3C2b4Ppd{BCe3OjeR?= NIPDWJEzPS93MD:xNFAhdk1? Mmr0NlQhcA>? M{\0ZmROW09? NVH6XnA4\W6qYX7j[ZMh[3m2YYLhZolv\S2rbnT1Z4VlKGGyb4D0c5Nqew>? NI\nfVIzOjh4OUi2PS=>
HCT116 MYDGeY5kfGmxbjDBd5NigQ>? MkS4NUDDvU1? MWiyOEBp MWPhZpJw\2G2ZYOgc4Yh[2WubDDjfYNt\SCjcoLld5TDqA>? NFTa[YEzOjVzMEW2NC=>
U2OS M{XxZ2Z2dmO2aX;uJGF{e2G7 M37lZ|EhyrWP NFznbZYzPCCq MlHSZYJzd2ejdHXzJI9nKGOnbHygZ5lkdGViYYLy[ZN1yqB? NHi0T4kzOjVzMEW2NC=>

... 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

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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