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 NHvZd29Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkfrNlAxNzJyMECgcm0> M2PJNlI1KGh? M4TWeIRm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= M3Pzd|I1OzV7NUK2
HCT115 NWnLfnFwT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVSyNFAwOjByMDDuUS=> MnXmNlQhcA>? NV;Jeot[\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l NU\u[ZNsOjR|NUm1NlY>
SW620 MlTaS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYOyNFAwOjByMDDuUS=> MXyyOEBp M3TyWoRm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= NIj2VmEzPDN3OUWyOi=>
IGROV-1 NUjGSoNzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mm[5NlAxNzJyMECgcm0> M1fWflI1KGh? NFrPSmhl\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= M4P0WVI1OzV7NUK2
HCT116 NULNR49iT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{fiW|IxOC9{MECwJI5O MX:yOEBp MlT4[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n M3W2dVI1OzV7NUK2
MCF10A Mm\OS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{W5U|IxOC9{MECwJI5O NWnCZZVROjRiaB?= MYrk[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? M3nQU|I1OzV7NUK2
MiaPaCa-2 MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2fhNFIxOC9{MECwJI5O NHLMTJMzPCCq MXvk[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? Mo\CNlQ{PTl3Mk[=
MDA-MB-231 MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2XNVFIxOC9{MECwJI5O NX3BV3dGOjRiaB?= M3PNSIRm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= MXGyOFM2QTV{Nh?=
HCC2998 NFzVd|dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NELTZYQzODBxMkCwNEBvVQ>? NUDvVHlpOjRiaB?= NUHrfWk3\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l Mnf4NlQ{PTl3Mk[=
U87 NWPwNHZ6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGD5UG0zODBxMkCwNEBvVQ>? MkHBNlQhcA>? NHr4Wmhl\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= M1jHd|I1OzV7NUK2
MDA-MB-435 M2S1Nmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHzJepMzODBxMkCwNEBvVQ>? NE\RT3IzPCCq MoDv[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n M2\VfVI1OzV7NUK2
SNB19 MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlfsNlAxNzJyMECgcm0> M{LjflI1KGh? MlO5[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n NXy1XFU1OjR|NUm1NlY>
U20S NUfRepdUT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mn31NlAxNzJyMECgcm0> MlfFNlQhcA>? NIHP[XFl\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= NUX6O3FJOjR|NUm1NlY>
A498 NWTROnJDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3XYPVIxOC9{MECwJI5O MmnFNlQhcA>? MnXj[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n MXOyOFM2QTV{Nh?=
TK10 M{fTVmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoDKNlAxNzJyMECgcm0> NX7UZmQ4OjRiaB?= MXXk[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? M{jmeVI1OzV7NUK2
AsPC-1 M3;LSmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUnTbm1yOjByL{KwNFAhdk1? NYLjdVhyOjRiaB?= NETwRWxl\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= M{H0NlI1OzV7NUK2
H23 NV7sXWRxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWK1NFAhdk1? M3HFSlI1KGh? NWLZeJpUTE2VTx?= NX7O[YFC\W6qYX7j[ZMhfGinIHPo[Y1we2Wwc3n0bZpifGmxbjD0c{BRVVh? NEmxOJAzPDFzM{W0PS=>
H1437 MmjlS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWK1NFAhdk1? M1zmXlI1KGh? MnHqSG1UVw>? NXfuUZFY\W6qYX7j[ZMhfGinIHPo[Y1we2Wwc3n0bZpifGmxbjD0c{BRVVh? M3niNVI1OTF|NUS5
H1993 NW\QRYpXT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1\JOlUxOCCwTR?= M1Px[FI1KGh? NHS5dYdFVVOR NHvkNllmdmijbnPld{B1cGViY3jlcY9{\W6|aYTpfoF1cW:wIITvJHBOYA>? NYnVTWxXOjRzMUO1OFk>
H1299 NFPqRXhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYOxTVJUPTByIH7N M{jmSlI1KGh? MmLWSG1UVw>? MVTlcohidmOnczD0bIUh[2inbX;z[Y5{cXSrenH0bY9vKHSxIGDNXC=> M2HkTlI1OTF|NUS5
AsPC-1 MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2nLbFExNTFyMECgcm0> M1TL[FI1NTR6aB?= MoWw[Y5p[W6lZYOgeIhmKGOqZX3vd4Vve2m2aYrheIlwdiC2bzDn[Y1kcXSjYnnu[S=> MnzsNlM5ODR2MkK=
MiaPaCa-2 NGL2[VlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXXHfZhsOTBvMUCwNEBvVQ>? NXz4Z3FvOjRvNEjo Mn7k[Y5p[W6lZYOgeIhmKGOqZX3vd4Vve2m2aYrheIlwdiC2bzDn[Y1kcXSjYnnu[S=> M3fsclI{QDB2NEKy
BxPC-3 M2G3cmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVPV[odTOTBvMUCwNEBvVQ>? MlfxNlQuPDiq MoTl[Y5p[W6lZYOgeIhmKGOqZX3vd4Vve2m2aYrheIlwdiC2bzDn[Y1kcXSjYnnu[S=> MUSyN|gxPDR{Mh?=
SKOV3 NIfJXXlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVywMlMhyrWP MWi4JIQ> NHHiZWF{\W6|aYTpfoV{KHSqZTDj[YxtKGyrbnXzJJRwKGenbXPpeIFjcW6nwrC= M2XmZ|I{PTR6Mk[5
OVCAR-8 NYSzWphOT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NX3Fb21ROC5|INM1US=> MYi4JIQ> M1zoOpNmdnOrdHn6[ZMhfGinIHPlcIwhdGmwZYOgeI8h\2WvY3n0ZYJqdmYEoB?= NILYV5YzOzV2OEK2PS=>
MV-4-11 NVWxZnNISXCxcITvd4l{KEG|c3H5 MljRNVAxNTdyMDDuUS=> M2rC[|Q5KGh? MnexbY5lfWOnczDhdI9xfG:|aYOg[I9{\SCmZYDlcoRmdnSueR?= NUPvb2RTOjN3M{[3NlE>
U937 MVfBdI9xfG:|aYOgRZN{[Xl? MkHuNVAxNTdyMDDuUS=> MYW0PEBp M4rwfYlv\HWlZYOgZZBweHSxc3nzJIRwe2ViZHXw[Y5l\W62bIm= NYLTVGhmOjN3M{[3NlE>
MOLM-13  M37iN2Fxd3C2b4Ppd{BCe3OjeR?= MX2xNFAuPzByIH7N NVrscGF7PDhiaB?= MmT1bY5lfWOnczDhdI9xfG:|aYOg[I9{\SCmZYDlcoRmdnSueR?= M37E[lI{PTN4N{Kx
A2058  M2HEbWNmdGxiVnnhZoltcXS7IFHzd4F6 NYm1[HFqOzdwNT2zNFAhdk1? NX\LVGlyPzJiaB?= MWLEUXNQ M3KwNpJm\HWlZYOgeIhmKE2NLUG3O|UhTUN3MNMgZpkhPS2ob3zkJJRwKGGwIHH2[ZJi\2Vib3[gOFUhdk1? NV;nfpZzOjNzNEi2PFQ>
H2009 MYPD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NIXobpQ2ODBibl2= MmDwO|IhcA>? M1rQSWROW09? M3nLdJJme3WudIOgbY4hTzFxUz3wbIF{\SCjY3P1cZVt[XSrb36gZ49u[mmwZXSge4l1cCCPSz2xO|c2 M{\CT|I{OTR6Nki0
Su.86.86 NFryN3RE\WyuIG\pZYJqdGm2eTDBd5NigQ>? NV\YfZRZPTByIH7N NE\QNpA4OiCq Ml62SG1UVw>? M4LIWZJme3WudIOgbY4hTzFxUz3wbIF{\SCjY3P1cZVt[XSrb36gZ49u[mmwZXSge4l1cCCPSz2xO|c2 MnLENlMyPDh4OES=
HRE MnXZR4VtdCCYaXHibYxqfHliQYPzZZk> NUnx[2NzPTByIH7N M{O0V|czKGh? M1\GRWROW09? MULy[ZN2dHS|IHnuJGcyN1NvcHjhd4Uh[WOldX31cIF1cW:wIHPvcYJqdmWmIIfpeIghVUtvMUe3OS=> M3[ydFI{OTR6Nki0
HMEC NYjPTllRS2WubDDWbYFjcWyrdImgRZN{[Xl? MVq1NFAhdk1? NW\kfId7PzJiaB?= MYjEUXNQ MnjodoV{fWy2czDpckBIOS:VLYDoZZNmKGGlY4XteYxifGmxbjDjc41jcW6nZDD3bZRpKE2NLUG3O|U> MXmyN|E1QDZ6NB?=
U2OS  MYfGeY5kfGmxbjDBd5NigQ>? MUSyJOK2VQ>? NYTTcolHOC1{NDDo MVnpcoR2[2W|IIDoc5NxcG:{eXzheIlwdiCxZjDDbIsyKGG2IIPldolv\SB|NEWgZZQh[m:2aDDjc45k\W62cnH0bY9veyCjczDlZZJtgSCjczCyJIgh[W[2ZYKgZYRucW6rc4TyZZRqd25? M1r5PFIzQTN5MUS3
U2OS  M2[yU2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHe5ToQxNTFyINM1US=> NYHTZ4VPOjRxNEigbC=> MnvWbY5pcWKrdIOgZ4VtdCCpcn;3eIgh\G:|ZTDk[ZBmdmSnboTsfS=> MoTyNlI6OzdzNEe=
U937 M2jYUmZ2dmO2aX;uJGF{e2G7 M2fybVExOC13MECgcm0> MXy0JIjDqA>? M2DmSYRm[3KnYYPld{B1cGViY4n0ZZJi[mmwZT3pcoR2[2WmIFPob|Eh[XW2b4Doc5NxcG:{eXzheIlwdiCjdDDT[ZIzQTcEoHHu[EBxemW4ZX70d{BE\GN{NVGg[I94dnKnZ4XsZZRqd25? NGXX[lIzOjh4OUi2PS=>
U937 MlTSSpVv[3Srb36gRZN{[Xl? Ml\WNVAxKG6P NHTqeG01KGkEoB?= M1PRbZJmfmW{c3XzJJRp\SCleYThdoFjcW6nLXnu[JVk\WRiaX7obYJqfGmxbjDv[uKhO0hvdHj5cYllcW6nIHnuZ49zeG:{YYTpc44hcW62bzDEUmE> MmK4NlI5Pjl6Nkm=
U937 NFO0[JVHfW6ldHnvckBCe3OjeR?= MoG2NVAxNTVyMDDuUS=> NWH3U|J[PCCqwrC= MYTpcoR2[2W|IHnuZ5Jm[XOnZDDwbI9{eGixconsZZRqd25ib3[gTFJCYA>? M3zFNlIzQDZ7OE[5
HL-60 MmLSRZBweHSxc3nzJGF{e2G7 MX2zNE8yODBxM{CwJI5O Ml[1NlQhcA>? M{\6OWROW09? NHfCeJdmdmijbnPld{BkgXSjcnHibY5mNWmwZIXj[YQh[XCxcITvd4l{ NGjBTnYzOjh4OUi2PS=>
ML-1 NVfI[VdkSXCxcITvd4l{KEG|c3H5 NWriS5N2OjVxNUCvNVAxKG6P M1P4O|I1KGh? M3TINWROW09? M33nPYVvcGGwY3XzJIN6fGG{YXLpcoUucW6mdXPl[EBieG:ydH;zbZM> NXzwXXFLOjJ6Nkm4Olk>
HCT116 NXzzO3FLTnWwY4Tpc44hSXO|YYm= MofQNUDDvU1? MorXNlQhcA>? MlnBZYJzd2ejdHXzJI9nKGOnbHygZ5lkdGViYYLy[ZN1yqB? M1\GeFIzPTFyNU[w
U2OS M1;4[mZ2dmO2aX;uJGF{e2G7 NI\URVUyKML3TR?= MYSyOEBp Mn:xZYJzd2ejdHXzJI9nKGOnbHygZ5lkdGViYYLy[ZN1yqB? MUmyNlUyODV4MB?=

... 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