MK-8776 (SCH 900776)

目录号:S2735

MK-8776 (SCH 900776) Chemical Structure

Molecular Weight(MW): 376.25

MK-8776 (SCH 900776)是一种选择性Chk1抑制剂,无细胞试验中IC50为3 nM,比作用于Chk2选择性高500倍。Phase 2。

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RMB 3015.42 现货
RMB 7966.05 现货
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客户使用该产品的4个实验数据:

  • 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.

  • HT29 cells were treated with 1 μM V411, 3 μM LY2603618 (LY), 3 μM MK-8776 (MK), 3 μM GNE-900 (GNE) or 0.3 μM ARRY-1A (ARRY) for 24 h. The fraction of γH2AX, pRPA32 (S4/S8), pChk1 (S317) or pChk2 (T68) positive nuclei were determined by single cell immunofluorescent imaging (n=4, mean ± SD). B. HT29 cells were treated as above for 2 or 24 h. Cell lysates were probed with the indicated antibodies by immunoblotting.

    Oncotarget, 2016, 7(51):85033-85048. 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.

产品安全说明书

Chk抑制剂选择性比较

生物活性

产品描述 MK-8776 (SCH 900776)是一种选择性Chk1抑制剂,无细胞试验中IC50为3 nM,比作用于Chk2选择性高500倍。Phase 2。
靶点
Chk1 [1]
(Cell-free assay)
CDK2 [1]
(Cell-free assay)
3 nM 0.16 μM
体外研究

SCH 900776是Chk2和CDK2的低效抑制剂,IC50分别为1.5 μM 和 0.16 μM。SCH 900776对细胞色素P450人肝微粒体亚型1A2,2C9,2C19,2D6,和3A4没有显著的抑制作用。羟基脲下暴露24小时后,SCH 900776诱导DNA复制能力剂量依赖性损失。SCH 900776增强γ-H2AX对羟基脲,5-氟尿嘧啶,和阿糖孢苷的响应。与抗代谢物结合,SCH 900776在2小时内诱导γ-H2AX的累积,表明复制叉瓦解,并且双链DNA断裂。此外,SCH 900776以剂量依赖的方式抑制Chk1 pS296自磷酸化的积累。增殖的WS1细胞暴露于SCH 900776,与Chk1 pS345快速的,剂量依赖性聚集相关,表明正常细胞的循环群诱导Chk1 pS345在暴露于SCH 900776后,是一部分无效循环,这也许通过AT-家族激酶和DNA-PK驱动。[1]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
U251 NIP3UVlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2PJV|IxOC9{MECwJI5O MUCyOEBp MXHk[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? MnPoNlQ{PTl3Mk[=
HCT115 NXrjbG1ST3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXiyNFAwOjByMDDuUS=> NFfCPWIzPCCq MXnk[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? MoLwNlQ{PTl3Mk[=
SW620 MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkDONlAxNzJyMECgcm0> MYiyOEBp MV3k[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? M4DNTVI1OzV7NUK2
IGROV-1 MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXeyNFAwOjByMDDuUS=> MkjsNlQhcA>? NEPTeZZl\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= M1i4XlI1OzV7NUK2
HCT116 NHTMTVFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NILrNmMzODBxMkCwNEBvVQ>? M3X6e|I1KGh? MlPB[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n NIfaVnAzPDN3OUWyOi=>
MCF10A NHi2XGpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUnMWpE2OjByL{KwNFAhdk1? NXHXWZl3OjRiaB?= M{\iZoRm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= MXmyOFM2QTV{Nh?=
MiaPaCa-2 MnrsS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3:xSVIxOC9{MECwJI5O MWCyOEBp MkHw[IVkemWjc3XzJJRp\SCLQ{WwJI9nKEenbXPpeIFjcW6n M{W3SFI1OzV7NUK2
MDA-MB-231 M4[xbmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MW[yNFAwOjByMDDuUS=> NUDxT3E3OjRiaB?= MVrk[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? NYO4cGxqOjR|NUm1NlY>
HCC2998 NXrYRVJMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEfLdXQzODBxMkCwNEBvVQ>? M{PL[FI1KGh? M1nBVIRm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= MoHlNlQ{PTl3Mk[=
U87 Mnu5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1;yUVIxOC9{MECwJI5O MX:yOEBp NHP1eGhl\WO{ZXHz[ZMhfGinIFnDOVAhd2ZiR3XtZ4l1[WKrbnW= NHvrRngzPDN3OUWyOi=>
MDA-MB-435 NVHzTJpNT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1roRVIxOC9{MECwJI5O MUSyOEBp MUTk[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? NFrzWHYzPDN3OUWyOi=>
SNB19 M{ntbWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{X4N|IxOC9{MECwJI5O MkjDNlQhcA>? M2jxPIRm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= MVSyOFM2QTV{Nh?=
U20S NFLZdJdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEL0fJgzODBxMkCwNEBvVQ>? NX7MUY1POjRiaB?= NWPlOnFW\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l NFjNPYQzPDN3OUWyOi=>
A498 Mlr5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2XGWlIxOC9{MECwJI5O NWrM[4dvOjRiaB?= M13RT4Rm[3KnYYPld{B1cGViSVO1NEBw\iCJZX3jbZRi[mmwZR?= MXmyOFM2QTV{Nh?=
TK10 NEm4NpZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHjifXgzODBxMkCwNEBvVQ>? MVSyOEBp MUTk[YNz\WG|ZYOgeIhmKEmFNUCgc4YhT2WvY3n0ZYJqdmV? NVTiNZNXOjR|NUm1NlY>
AsPC-1 M3LDNGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmnJNlAxNzJyMECgcm0> MnTjNlQhcA>? NUfEWmJ1\GWlcnXhd4V{KHSqZTDJR|UxKG:oIFflcYNqfGGkaX7l M3foUVI1OzV7NUK2
H23 NGPxSnVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NH\RTXk2ODBibl2= M2HOZVI1KGh? NGi1PZRFVVOR MWrlcohidmOnczD0bIUh[2inbX;z[Y5{cXSrenH0bY9vKHSxIGDNXC=> M2Pl[lI1OTF|NUS5
H1437 NUfJOlJPT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXzTNGJ[PTByIH7N MWmyOEBp NEXWPGNFVVOR NWrhUng4\W6qYX7j[ZMhfGinIHPo[Y1we2Wwc3n0bZpifGmxbjD0c{BRVVh? NU\vbIN[OjRzMUO1OFk>
H1993 M3\icWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MW[1NFAhdk1? MXyyOEBp M3f1ZmROW09? MoTO[Y5p[W6lZYOgeIhmKGOqZX3vd4Vve2m2aYrheIlwdiC2bzDQUXg> NUXQWodrOjRzMUO1OFk>
H1299 MnHHS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3zQTVUxOCCwTR?= NVXBVW57OjRiaB?= NFfBXFhFVVOR NXOxNnpy\W6qYX7j[ZMhfGinIHPo[Y1we2Wwc3n0bZpifGmxbjD0c{BRVVh? NHfsZYUzPDFzM{W0PS=>
AsPC-1 NHvTZVVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2jIXVExNTFyMECgcm0> NVrVO2J6OjRvNEjo MnSy[Y5p[W6lZYOgeIhmKGOqZX3vd4Vve2m2aYrheIlwdiC2bzDn[Y1kcXSjYnnu[S=> NIrGNZQzOzhyNESyNi=>
MiaPaCa-2 MnXVS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXyxNE0yODByIH7N M3ftdlI1NTR6aB?= MULlcohidmOnczD0bIUh[2inbX;z[Y5{cXSrenH0bY9vKHSxIHflcYNqfGGkaX7l MXGyN|gxPDR{Mh?=
BxPC-3 NFzRSFJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4XHVVExNTFyMECgcm0> MWSyOE01QGh? MkPr[Y5p[W6lZYOgeIhmKGOqZX3vd4Vve2m2aYrheIlwdiC2bzDn[Y1kcXSjYnnu[S=> NH25TpEzOzhyNESyNi=>
SKOV3 NFTrfJJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mm\xNE4{KML3TR?= MWi4JIQ> NXrsWmdGe2Wwc3n0bZpmeyC2aHWgZ4VtdCCuaX7ld{B1dyCpZX3jbZRi[mmwZdMg NV\lS3dMOjN3NEiyOlk>
OVCAR-8 NGL0R3dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M17NNVAvOyEEtV2= MU[4JIQ> M1XjOZNmdnOrdHn6[ZMhfGinIHPlcIwhdGmwZYOgeI8h\2WvY3n0ZYJqdmYEoB?= MWqyN|U1QDJ4OR?=
MV-4-11 NYHle5hiSXCxcITvd4l{KEG|c3H5 NGjtbGgyODBvN{CwJI5O M3u0eVQ5KGh? NIPQ[oxqdmS3Y3XzJIFxd3C2b4Ppd{Bld3OnIHTldIVv\GWwdHz5 MWSyN|U{Pjd{MR?=
U937 Mne3RZBweHSxc3nzJGF{e2G7 MXixNFAuPzByIH7N NF7Ee4I1QCCq NWrMN5ROcW6mdXPld{BieG:ydH;zbZMh\G:|ZTDk[ZBmdmSnboTsfS=> MlrJNlM2OzZ5MkG=
MOLM-13  MULBdI9xfG:|aYOgRZN{[Xl? MkjsNVAxNTdyMDDuUS=> MVS0PEBp M1jOZ4lv\HWlZYOgZZBweHSxc3nzJIRwe2ViZHXw[Y5l\W62bIm= NWTSWno6OjN3M{[3NlE>
A2058  M3PDSGNmdGxiVnnhZoltcXS7IFHzd4F6 MkO1N|cvPS1|MECgcm0> NGnR[o84OiCq M3zrd2ROW09? MWXy[YR2[2W|IITo[UBOUy1zN{e1JGVEPTEEoHL5JFUu\m:uZDD0c{BidiCjdnXyZYdmKG:oIES1JI5O MoGzNlMyPDh4OES=
H2009 MWfD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NFTNXWI2ODBibl2= MV:3NkBp M{Oy[WROW09? NHzMe2Rz\XO3bITzJIlvKEdzL2OtdIhie2ViYXPjeY12dGG2aX;uJINwdWKrbnXkJJdqfGhiTVutNVc4PQ>? MV:yN|E1QDZ6NB?=
Su.86.86 NXzXPJZ[S2WubDDWbYFjcWyrdImgRZN{[Xl? MWq1NFAhdk1? MkXqO|IhcA>? NEHlOVNFVVOR NVe0SoVDemW|dXz0d{BqdiCJMT;TMZBp[XOnIHHjZ5VufWyjdHnvckBkd22kaX7l[EB4cXSqIF3LMVE4PzV? M4rsRVI{OTR6Nki0
HRE M{\KW2NmdGxiVnnhZoltcXS7IFHzd4F6 M3y2blUxOCCwTR?= MnG4O|IhcA>? NXK3NWZPTE2VTx?= NGfoZpVz\XO3bITzJIlvKEdzL2OtdIhie2ViYXPjeY12dGG2aX;uJINwdWKrbnXkJJdqfGhiTVutNVc4PQ>? MkjrNlMyPDh4OES=
HMEC MWDD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NYT1PVZ5PTByIH7N MVS3NkBp M1Tp[WROW09? MmH6doV{fWy2czDpckBIOS:VLYDoZZNmKGGlY4XteYxifGmxbjDjc41jcW6nZDD3bZRpKE2NLUG3O|U> M2P5eVI{OTR6Nki0
U2OS  MV;GeY5kfGmxbjDBd5NigQ>? M3zxW|IhyrWP MUmwMVI1KGh? M4S1SYlv\HWlZYOgdIhwe3Cqb4L5cIF1cW:wIH;mJGNpczFiYYSgd4VzcW6nIEO0OUBifCCkb4ToJINwdmOnboTyZZRqd26|IHHzJIViemy7IHHzJFIhcCCjZoTldkBi\G2rbnnzeJJifGmxbh?= MVKyNlk{PzF2Nx?=
U2OS  NFnNUHRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUmwMVExKML3TR?= M3fjXlI1NzR6IHi= M1;uN4lvcGmkaYTzJINmdGxiZ4Lve5RpKGSxc3Wg[IVx\W6mZX70cJk> NHz6fHgzOjl|N{G0Oy=>
U937 NVK5UZlTTnWwY4Tpc44hSXO|YYm= NYXVPWdIOTByLUWwNEBvVQ>? M2\UdVQhcMLi MVrk[YNz\WG|ZYOgeIhmKGO7dHHyZYJqdmVvaX7keYNm\CCFaHuxJIF2fG:yaH;zdIhwenmuYYTpc44h[XRiU3XyNlk3yqCjbnSgdJJmfmWwdIOgR4RkOjWDIHTve45z\We3bHH0bY9v MUiyNlg3QTh4OR?=
U937 MnrMSpVv[3Srb36gRZN{[Xl? M17HRlExOCCwTR?= NEXnWoI1KGkEoB?= Ml3UdoV3\XK|ZYOgeIhmKGO7dHHyZYJqdmVvaX7keYNm\CCrbnjpZol1cW:wIH;mxsA{UC22aIntbYRqdmViaX7jc5Jxd3KjdHnvckBqdnSxIFTORS=> MYeyNlg3QTh4OR?=
U937 MY\GeY5kfGmxbjDBd5NigQ>? NHLPdpMyODBvNUCwJI5O NHi0d4Y1KGkEoB?= Mn7QbY5lfWOnczDpcoNz\WG|ZXSgdIhwe3Cqb4L5cIF1cW:wIH;mJGgzSVh? Mn\xNlI5Pjl6Nkm=
HL-60 MUXBdI9xfG:|aYOgRZN{[Xl? NX\pXmhROzBxMUCwM|MxOCCwTR?= MVSyOEBp NFrmPFZFVVOR NGCwXYVmdmijbnPld{BkgXSjcnHibY5mNWmwZIXj[YQh[XCxcITvd4l{ M2[xdVIzQDZ7OE[5
ML-1 MWPBdI9xfG:|aYOgRZN{[Xl? NWPiTG9IOjVxNUCvNVAxKG6P Mn[wNlQhcA>? MXTEUXNQ NVzaflNi\W6qYX7j[ZMh[3m2YYLhZolv\S2rbnT1Z4VlKGGyb4D0c5Nqew>? M3THNVIzQDZ7OE[5
HCT116 MljzSpVv[3Srb36gRZN{[Xl? MlTvNUDDvU1? MmTGNlQhcA>? M3jnVIFjem:pYYTld{Bw\iClZXzsJIN6[2ynIHHydoV{fMLi MYiyNlUyODV4MB?=
U2OS MYHGeY5kfGmxbjDBd5NigQ>? NGPWZVEyKML3TR?= MnfJNlQhcA>? M3HCcoFjem:pYYTld{Bw\iClZXzsJIN6[2ynIHHydoV{fMLi Mnm0NlI2OTB3NkC=

... Click to View More Cell Line Experimental Data

体内研究 相对于gemcitabine或SCH 900776单独给药,Gemcitabine给药30分钟后,4 mg/kg SCH 900776足以诱导γ-H2AX生物标志物,而8 mg/kg增强肿瘤药效动力学和退化响应。递增剂量的SCH 900776 (16 mg/kg和32 mg/kg)诱导肿瘤响应持续改进。重要的是,在BALB/c 小鼠体内,SCH 900776的剂量与强的生物标志物活化相关,而提高的肿瘤响应与gemcitabine对血液学指标增强的毒性无关。[1]

推荐的实验操作(此推荐来自于公开的文献所以Selleck并不保证其有效性)

动物实验:[1]
+ 展开
  • Animal Models: 皮下注射A2780 或 MiaPaCa2细胞的额雌性裸鼠
  • Formulation: 在 20% 羟丙基β-环糊精中形成
  • Dosages: ~50 mg/kg
  • Administration: 腹腔内注射
    (Only for Reference)

溶解度 (25°C)

体外 DMSO 3 mg/mL (7.97 mM)
Water Insoluble
Ethanol Insoluble
体内 从左到右依次将纯溶剂加入产品,现配现用(数据来自Selleck实验检测而非文献):
4% DMSO+30% propylene glycol
5 mg/mL

* 溶解度检测是由Selleck技术部门检测的,可能会和文献中提供的溶解度有所差异,这是由于生产工艺和批次不同产生的正常现象。请按照顺序依次加入各个纯溶剂。

化学数据

分子量 376.25
化学式

C15H18BrN7

CAS号 891494-63-6
稳定性 powder
in solvent
别名 N/A

计算器

摩尔浓度计算器

摩尔浓度计算器

本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系,公式为:

质量 (g) = 浓度 (mol/L) x 体积 (L) x 分子量 (g/mol)

摩尔浓度计算公式

  • 质量
    浓度
    体积
    分子量

*在配置溶液时,请务必参考Selleck产品标签上、MSDS / COA(可在Selleck的产品页面获得)批次特异的分子量使用本工具。

稀释计算器

稀释计算器

用本工具协助配置特定浓度的溶液,使用的计算公式为:

开始浓度 x 开始体积 = 最终浓度 x 最终体积

稀释公式

稀释公式一般简略地表示为: C1V1 = C2V2 ( 输入 输出 )

  • C1
    V1
    C2
    V2

在配置溶液时,请务必参考Selleck产品标签上、MSDS / COA(可在Selleck的产品页面获得)批次特异的分子量使用本工具。.

连续稀释计算器方程

  • 连续稀释

  • 计算结果

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):
分子量计算器

分子量计算器

通过输入化合物的化学式来计算其分子量:

总分子量:g/mol

注:化学分子式大小写敏感。C10H16N2O2 c10h16n2o2

摩尔浓度计算器

质量 浓度 体积 分子量
计算

临床试验信息

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT00907517 Terminated Myelogenous Leukemia Acute|Leukemia Lymphocytic Acute|Leukemia Lymphoblastic Acute Philadelphia-Positive|Myelogenous Leukemia Chronic Aggressive Phase Merck Sharp & Dohme Corp. July 29 2009 Phase 1
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
NCT00779584 Completed Hodgkin Disease|Lymphoma Non-Hodgkin|Neoplasms Merck Sharp & Dohme Corp. October 17 2008 Phase 1

技术支持

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常见问题及建议解决方法

  • 问题 1:

    I would like to know whether your product S2735 is the optically pure R enantiomer or whether it is a racemic mix.

  • 回答:

    Our S2735 MK-8776 (SCH 900776) is R enantiomer.

Chk Signaling Pathway Map

Chk Inhibitors with Unique Features

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID