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

Choose Selective Chk Inhibitors

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 NEK2e|FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXfOc|k1OjByL{KwNFAhdk1? NX\rO5JqOjRiaB?= MV\k[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? NEfhcXQzPDN3OUWyOi=>
HCT115 MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWrsW|g3OjByL{KwNFAhdk1? M{KwNVI1KGh? MmOw[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n NGHBTYYzPDN3OUWyOi=>
SW620 M2LjNWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MW[yNFAwOjByMDDuUS=> M{XjdFI1KGh? MoDQ[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n NX3NfWZ4OjR|NUm1NlY>
IGROV-1 NG\3UY5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVX1UlFROjByL{KwNFAhdk1? Mm\ENlQhcA>? NHnQc4hl\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= Mn3YNlQ{PTl3Mk[=
HCT116 M4nV[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NH\TbFEzODBxMkCwNEBvVQ>? M2rDbVI1KGh? NY\wRoR[\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l NF:zRoczPDN3OUWyOi=>
MCF10A Mm\4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkL6NlAxNzJyMECgcm0> NVT0XmxyOjRiaB?= NF2zTWZl\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= NWTW[FdvOjR|NUm1NlY>
MiaPaCa-2 NX\NcnFCT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIXzOGIzODBxMkCwNEBvVQ>? NYrqV2YxOjRiaB?= Mkmw[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n Moq0NlQ{PTl3Mk[=
MDA-MB-231 MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mo\4NlAxNzJyMECgcm0> NF7pZYszPCCq NIXCRVZl\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= NWO2eFRlOjR|NUm1NlY>
HCC2998 NGrOcIdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXmyNFAwOjByMDDuUS=> NXr3XZJwOjRiaB?= MmrN[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n M3mwcVI1OzV7NUK2
U87 NEe5SXVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVPOb3pMOjByL{KwNFAhdk1? MVeyOEBp MkPv[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n M3jZXVI1OzV7NUK2
MDA-MB-435 NUjMOJBxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXeyNFAwOjByMDDuUS=> MoTNNlQhcA>? M3zYOYRm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= NIHTPYszPDN3OUWyOi=>
SNB19 M4P4PGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVfi[5VHOjByL{KwNFAhdk1? NIGzenUzPCCq MWPk[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? M4L6[lI1OzV7NUK2
U20S NHGxU5VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFTUXlIzODBxMkCwNEBvVQ>? Ml30NlQhcA>? MkTD[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n NEXXPGczPDN3OUWyOi=>
A498 NVHxUW5WT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlnDNlAxNzJyMECgcm0> MofzNlQhcA>? Mnjj[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n MlXiNlQ{PTl3Mk[=
TK10 NXL1fI1bT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVXTbVE5OjByL{KwNFAhdk1? Mk\pNlQhcA>? NWDYPXB3\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l NInzSogzPDN3OUWyOi=>
AsPC-1 NYPvNlZMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoTtNlAxNzJyMECgcm0> NXLYVJhuOjRiaB?= M3LkboRm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= NID6fHgzPDN3OUWyOi=>
H23 NFzqWnlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnroOVAxKG6P NHfGXWIzPCCq NVLuWoVlTE2VTx?= M3:3coVvcGGwY3XzJJRp\SClaHXtc5NmdnOrdHn6ZZRqd25idH:gVG1Z M33VXFI1OTF|NUS5
H1437 MoLiS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3rIZlUxOCCwTR?= NWPqPJN4OjRiaB?= NILpNXpFVVOR M2LtUIVvcGGwY3XzJJRp\SClaHXtc5NmdnOrdHn6ZZRqd25idH:gVG1Z NFTGOG0zPDFzM{W0PS=>
H1993 M4i4TWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEHVWnk2ODBibl2= MU[yOEBp M4DY[GROW09? MkX1[Y5p[W6lZYOgeIhmKGOqZX3vd4Vve2m2aYrheIlwdiC2bzDQUXg> MWSyOFEyOzV2OR?=
H1299 MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXvwc2R5PTByIH7N MljhNlQhcA>? NHzKN2hFVVOR NXT2UHV2\W6qYX7j[ZMhfGinIHPo[Y1we2Wwc3n0bZpifGmxbjD0c{BRVVh? NELlT|gzPDFzM{W0PS=>
AsPC-1 M4Tobmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXSxNE0yODByIH7N MkTrNlQuPDiq NWnsUIRL\W6qYX7j[ZMhfGinIHPo[Y1we2Wwc3n0bZpifGmxbjD0c{Bo\W2laYThZolv\Q>? MkXlNlM5ODR2MkK=
MiaPaCa-2 NY\pPVRUT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXexNE0yODByIH7N M3roTFI1NTR6aB?= M{PvXIVvcGGwY3XzJJRp\SClaHXtc5NmdnOrdHn6ZZRqd25idH:g[4Vu[2m2YXLpcoU> MYeyN|gxPDR{Mh?=
BxPC-3 MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4C1TlExNTFyMECgcm0> NYLubVFVOjRvNEjo Mlvw[Y5p[W6lZYOgeIhmKGOqZX3vd4Vve2m2aYrheIlwdiC2bzDn[Y1kcXSjYnnu[S=> NUPOfotbOjN6MES0NlI>
SKOV3 NGjBNlFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUX0UpNUOC5|INM1US=> MX64JIQ> NX\hZoY3e2Wwc3n0bZpmeyC2aHWgZ4VtdCCuaX7ld{B1dyCpZX3jbZRi[mmwZdMg NGXqfZEzOzV2OEK2PS=>
OVCAR-8 NITwPWZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1nve|AvOyEEtV2= NF7wT2Q5KGR? Mlq0d4Vve2m2aYrld{B1cGViY3XscEBtcW6nczD0c{Bo\W2laYThZolv\cLi NVSxW3YxOjN3NEiyOlk>
MV-4-11 MVTBdI9xfG:|aYOgRZN{[Xl? Mli0NVAxNTdyMDDuUS=> NEPCXIM1QCCq NFHIdpRqdmS3Y3XzJIFxd3C2b4Ppd{Bld3OnIHTldIVv\GWwdHz5 NX;SclZFOjN3M{[3NlE>
U937 M4m5XmFxd3C2b4Ppd{BCe3OjeR?= Mn3CNVAxNTdyMDDuUS=> NF\NWI01QCCq NHrXV|dqdmS3Y3XzJIFxd3C2b4Ppd{Bld3OnIHTldIVv\GWwdHz5 NXHXZ|U4OjN3M{[3NlE>
MOLM-13  MWXBdI9xfG:|aYOgRZN{[Xl? MVuxNFAuPzByIH7N M37hN|Q5KGh? NUj2WFd2cW6mdXPld{BieG:ydH;zbZMh\G:|ZTDk[ZBmdmSnboTsfS=> M{LlcFI{PTN4N{Kx
A2058  NFj3cHFE\WyuIG\pZYJqdGm2eTDBd5NigQ>? M1PGOlM4NjVvM{CwJI5O MoXpO|IhcA>? Mn;ISG1UVw>? MWDy[YR2[2W|IITo[UBOUy1zN{e1JGVEPTEEoHL5JFUu\m:uZDD0c{BidiCjdnXyZYdmKG:oIES1JI5O NIXJdoYzOzF2OE[4OC=>
H2009 MXzD[YxtKF[rYXLpcIl1gSCDc4PhfS=> MlLZOVAxKG6P NFfaNpY4OiCq NHfyfotFVVOR NEjzNm9z\XO3bITzJIlvKEdzL2OtdIhie2ViYXPjeY12dGG2aX;uJINwdWKrbnXkJJdqfGhiTVutNVc4PQ>? MoDqNlMyPDh4OES=
Su.86.86 MoPRR4VtdCCYaXHibYxqfHliQYPzZZk> Mly5OVAxKG6P NUD6PI12PzJiaB?= M33icWROW09? MX3y[ZN2dHS|IHnuJGcyN1NvcHjhd4Uh[WOldX31cIF1cW:wIHPvcYJqdmWmIIfpeIghVUtvMUe3OS=> NUTMdI0yOjNzNEi2PFQ>
HRE NYe1cFBUS2WubDDWbYFjcWyrdImgRZN{[Xl? MlLwOVAxKG6P M3jKUlczKGh? NFvqZ3FFVVOR NV\EdWN2emW|dXz0d{BqdiCJMT;TMZBp[XOnIHHjZ5VufWyjdHnvckBkd22kaX7l[EB4cXSqIF3LMVE4PzV? NFLKNXAzOzF2OE[4OC=>
HMEC M3npSmNmdGxiVnnhZoltcXS7IFHzd4F6 M3O1XFUxOCCwTR?= MUi3NkBp MkDiSG1UVw>? MYHy[ZN2dHS|IHnuJGcyN1NvcHjhd4Uh[WOldX31cIF1cW:wIHPvcYJqdmWmIIfpeIghVUtvMUe3OS=> MnXRNlMyPDh4OES=
U2OS  MnjWSpVv[3Srb36gRZN{[Xl? MV:yJOK2VQ>? NVzYdlRHOC1{NDDo MlrNbY5lfWOnczDwbI9{eGixconsZZRqd25ib3[gR4hsOSCjdDDz[ZJqdmViM{S1JIF1KGKxdHigZ49v[2WwdILheIlwdnNiYYOg[YFzdHliYYOgNkBpKGGodHXyJIFldWmwaYP0doF1cW:w NHjpXWozOjl|N{G0Oy=>
U2OS  M{ToSWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYD4WotrOC1zMDFCuW0> NYjtRYRGOjRxNEigbC=> Ml7vbY5pcWKrdIOgZ4VtdCCpcn;3eIgh\G:|ZTDk[ZBmdmSnboTsfS=> NHPaenYzOjl|N{G0Oy=>
U937 NFvxSFBHfW6ldHnvckBCe3OjeR?= MWKxNFAuPTByIH7N MVu0JIjDqA>? NIfWSJNl\WO{ZXHz[ZMhfGinIHP5eIFz[WKrbnWtbY5lfWOnZDDDbIsyKGG3dH;wbI9{eGixconsZZRqd25iYYSgV4VzOjl4wrDhcoQheHKndnXueJMhS2SlMkXBJIRwf26{ZXf1cIF1cW:w NXrUR5lzOjJ6Nkm4Olk>
U937 MnXGSpVv[3Srb36gRZN{[Xl? MXKxNFAhdk1? MVO0JIjDqA>? MV\y[ZZmenOnczD0bIUh[3m2YYLhZolv\S2rbnT1Z4VlKGmwaHnibZRqd25ib3dCpFNJNXSqeX3p[Ilv\SCrbnPvdpBwemG2aX;uJIlvfG9iRF7B NGHqeZczOjh4OUi2PS=>
U937 MXLGeY5kfGmxbjDBd5NigQ>? NYnXT|JtOTByLUWwNEBvVQ>? M1nsS|QhcMLi M1Pvd4lv\HWlZYOgbY5kemWjc3XkJJBpd3OyaH;yfYxifGmxbjDv[kBJOkG[ MnfHNlI5Pjl6Nkm=
HL-60 NYmzSZlzSXCxcITvd4l{KEG|c3H5 MkLxN|AwOTByL{OwNEBvVQ>? NHXPZm8zPCCq NGKwboZFVVOR M{fOSYVvcGGwY3XzJIN6fGG{YXLpcoUucW6mdXPl[EBieG:ydH;zbZM> NVrKS2dpOjJ6Nkm4Olk>
ML-1 MXnBdI9xfG:|aYOgRZN{[Xl? MWeyOU82OC9zMECgcm0> MUKyOEBp NHHRO5hFVVOR M3[wUoVvcGGwY3XzJIN6fGG{YXLpcoUucW6mdXPl[EBieG:ydH;zbZM> M1nSZ|IzQDZ7OE[5
HCT116 NGHHSplHfW6ldHnvckBCe3OjeR?= NF7u[WQyKML3TR?= NFPLW5kzPCCq MUnhZpJw\2G2ZYOgc4Yh[2WubDDjfYNt\SCjcoLld5TDqA>? NYXv[49TOjJ3MUC1OlA>
U2OS MmPhSpVv[3Srb36gRZN{[Xl? M2jBNVEhyrWP M4CwZVI1KGh? MVPhZpJw\2G2ZYOgc4Yh[2WubDDjfYNt\SCjcoLld5TDqA>? MmG3NlI2OTB3NkC=

... 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 slightly soluble or insoluble
Ethanol slightly soluble or 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
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