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Avagacestat (BMS-708163)

中文名稱：塞來(lái)西布

Avagacestat (BMS-708163)是口服生物有效的，選擇性的γ-分泌酶抑制劑，作用于Aβ40和Aβ42時(shí)，IC50分別為0.3 nM和0.27 nM，比作用于Notch選擇性高193倍。Phase 2。

Avagacestat (BMS-708163) Chemical Structure

Avagacestat (BMS-708163) Chemical Structure

CAS: 1146699-66-2

規(guī)格 價(jià)格 庫(kù)存 購(gòu)買(mǎi)數(shù)量
5mg 1403.72 現(xiàn)貨
10mg 2620.13 現(xiàn)貨
50mg 7967.17 現(xiàn)貨
200mg 15700 現(xiàn)貨
1g 39900 現(xiàn)貨
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Avagacestat (BMS-708163)相關(guān)產(chǎn)品

細(xì)胞實(shí)驗(yàn)數(shù)據(jù)示例

細(xì)胞系 實(shí)驗(yàn)類型 給藥濃度 孵育時(shí)間 活性描述 文獻(xiàn)信息
human IMR32 cell Function assay 2 h Inhibition of gamma-secretase in human IMR32 cell membrane using APP as substrate after 2 hrs by ELISA, IC50=0.13 nM 23312944
human IMR32 cell Function assay 2 h Inhibition of gamma-secretase in human IMR32 cell membrane using Notch as substrate after 2 hrs by ELISA, IC50=1.5 nM 23312944
human H4 cells Function assay Inhibition of gamma secretase-mediated amyloid beta42 production in human H4 cells expressing human APP swedish mutant, IC50=0.225 μM 22420884
HEK293 cells Function assay Inhibition of gamma-secretase in HEK293 cells after overnight incubation by Western blotting analysis, IC50=1.2 nM 23312944
CHO cells Function assay Inhibition of gamma-secretase in CHO cells assessed expressing APPSw assessed as inhibition of amyloid beta(1 to x) secretion after overnight incubation by ELISA, ED50=1.2 nM 23713656
human 786-0 cell Growth inhibition assay Inhibition of human 786-0 cell growth in a cell viability assay, IC50=0.32173 μM SANGER
human NCI-H810 cell Growth inhibition assay Inhibition of human NCI-H810 cell growth in a cell viability assay, IC50=0.42598 μM SANGER
human IGR-1 cell Growth inhibition assay Inhibition of human IGR-1 cell growth in a cell viability assay, IC50=1.04778 μM SANGER
human SK-MEL-3 cell Growth inhibition assay Inhibition of human SK-MEL-3 cell growth in a cell viability assay, IC50=1.49922 μM SANGER
human HT-1080 cell Growth inhibition assay Inhibition of human HT-1080 cell growth in a cell viability assay, IC50=2.48764 μM SANGER
human NCI-H23 cell Growth inhibition assay Inhibition of human NCI-H23 cell growth in a cell viability assay, IC50=3.9322 μM SANGER
human Calu-6 cell Growth inhibition assay Inhibition of human Calu-6 cell growth in a cell viability assay, IC50=4.96014 μM SANGER
human CAPAN-1 cell Growth inhibition assay Inhibition of human CAPAN-1 cell growth in a cell viability assay, IC50=5.17886 μM SANGER
human COLO-668 cell Growth inhibition assay Inhibition of human COLO-668 cell growth in a cell viability assay, IC50=5.40221 μM SANGER
human TE-6 cell Growth inhibition assay Inhibition of human TE-6 cell growth in a cell viability assay, IC50=6.19082 μM SANGER
human LCLC-97TM1 cell Growth inhibition assay Inhibition of human LCLC-97TM1 cell growth in a cell viability assay, IC50=10.0886 μM SANGER
human CAS-1 cell Growth inhibition assay Inhibition of human CAS-1 cell growth in a cell viability assay, IC50=13.671 μM SANGER
human RPMI-2650 cell Growth inhibition assay Inhibition of human RPMI-2650 cell growth in a cell viability assay, IC50=13.8124 μM SANGER
human MDA-MB-157 cell Growth inhibition assay Inhibition of human MDA-MB-157 cell growth in a cell viability assay, IC50=14.2431 μM SANGER
human KINGS-1 cell Growth inhibition assay Inhibition of human KINGS-1 cell growth in a cell viability assay, IC50=14.3762 μM SANGER
human BB49-HNC cell Growth inhibition assay Inhibition of human BB49-HNC cell growth in a cell viability assay, IC50=14.4138 μM SANGER
human SK-UT-1 cell Growth inhibition assay Inhibition of human SK-UT-1 cell growth in a cell viability assay, IC50=14.6882 μM SANGER
human EW-11 cell Growth inhibition assay Inhibition of human EW-11 cell growth in a cell viability assay, IC50=14.8832 μM SANGER
human D-502MG cell Growth inhibition assay Inhibition of human D-502MG cell growth in a cell viability assay, IC50=14.9034 μM SANGER
human MMAC-SF cell Growth inhibition assay Inhibition of human MMAC-SF cell growth in a cell viability assay, IC50=15.0833 μM SANGER
human NCI-H1648 cell Growth inhibition assay Inhibition of human NCI-H1648 cell growth in a cell viability assay, IC50=15.778 μM SANGER
human NCI-H292 cell Growth inhibition assay Inhibition of human NCI-H292 cell growth in a cell viability assay, IC50=15.8806 μM SANGER
human NMC-G1 cell Growth inhibition assay Inhibition of human NMC-G1 cell growth in a cell viability assay, IC50=16.6293 μM SANGER
human SAS cell Growth inhibition assay Inhibition of human SAS cell growth in a cell viability assay, IC50=17.7812 μM SANGER
human HCT-116 cell Growth inhibition assay Inhibition of human HCT-116 cell growth in a cell viability assay, IC50=18.7965 μM SANGER
human SBC-5 cell Growth inhibition assay Inhibition of human SBC-5 cell growth in a cell viability assay, IC50=19.03 μM SANGER
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生物活性

產(chǎn)品描述 Avagacestat (BMS-708163)是口服生物有效的，選擇性的γ-分泌酶抑制劑，作用于Aβ40和Aβ42時(shí)，IC50分別為0.3 nM和0.27 nM，比作用于Notch選擇性高193倍。Phase 2。
特性 BMS-708163作用于Notch過(guò)程似乎比semagacestat (LY450139)效果要好，且所需量要少
靶點(diǎn)
Aβ42 [1]
(in H4-8Sw cells)		 Aβ40 [1]
(in H4-8Sw cells)
0.27 nM 0.3 nM
體外研究(In Vitro)
體外研究活性 BMS-708163 抑制Notch 過(guò)程時(shí)顯示出低選擇性。 [1]
體內(nèi)研究(In Vivo)
體內(nèi)研究活性 鼠和犬口服處理BMS-708163 明顯且長(zhǎng)期降低腦，血漿，腦脊液中的Aβ40 水平。BMS-708163作用于犬時(shí)，沒(méi)有劑量限制影響(用3 mg/kg BMS-708163處理6個(gè)月內(nèi)的犬)。[1]
動(dòng)物實(shí)驗(yàn) Animal Models 雌性Harlan Sprague Dawley鼠或 ATM-405-142K9，7到10月大的 na?ve II級(jí)犬。
Dosages 10 mg/kg (鼠) 或2.5 mg/kg (犬)
Administration 每天口服飼喂
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT01002079 Completed
Alzheimer Disease
Bristol-Myers Squibb|PRA Health Sciences
 August 2010 Phase 1
NCT01057030 Completed
Alzheimer Disease
Bristol-Myers Squibb
 March 2010 Phase 1
NCT01042314 Completed
Alzheimer Disease
Bristol-Myers Squibb
 January 2010 Phase 1
NCT01039194 Completed
Alzheimer Disease
Bristol-Myers Squibb
 January 2010 Phase 1
NCT00979316 Completed
Alzheimer Disease
Bristol-Myers Squibb
 September 2009 Phase 1
NCT00890890 Terminated
Alzheimer''s Disease
Bristol-Myers Squibb
 May 2009 Phase 2

化學(xué)信息&溶解度

分子量 520.88 分子式

C20H17ClF4N4O4S
CAS號(hào) 1146699-66-2 SDF Download Avagacestat (BMS-708163) SDF
Smiles C1=CC(=CC=C1S(=O)(=O)N(CC2=C(C=C(C=C2)C3=NOC=N3)F)C(CCC(F)(F)F)C(=O)N)Cl
儲(chǔ)存條件(自收到貨起)

體外溶解度
批次：

DMSO : 104 mg/mL ( (199.66 mM) ；DMSO吸濕會(huì)降低化合物溶解度，請(qǐng)使用新開(kāi)封DMSO)

Water : Insoluble

Ethanol : Insoluble

摩爾濃度計(jì)算器

體內(nèi)溶解度
批次：

現(xiàn)配現(xiàn)用，請(qǐng)按從左到右的順序依次添加，澄清后再加入下一溶劑

 動(dòng)物體內(nèi)配方計(jì)算器

實(shí)驗(yàn)計(jì)算

摩爾濃度計(jì)算器

質(zhì)量 濃度 體積 分子量

動(dòng)物體內(nèi)配方計(jì)算器（澄清溶液）

第一步：請(qǐng)輸入基本實(shí)驗(yàn)信息（考慮到實(shí)驗(yàn)過(guò)程中的損耗，建議多配一只動(dòng)物的藥量）

mg/kg g μL 只

第二步：請(qǐng)輸入動(dòng)物體內(nèi)配方組成（配方適用于不溶于水的藥物；不同批次藥物配方比例不同，請(qǐng)聯(lián)系Selleck為您提供正確的澄清溶液配方）

% DMSO % % Tween 80 % ddH2O
%DMSO %

計(jì)算結(jié)果：

工作液濃度： mg/ml；

DMSO母液配制方法： mg 藥物溶于μL DMSO溶液（母液濃度mg/mL，注：如該濃度超過(guò)該批次藥物DMSO溶解度，請(qǐng)先聯(lián)系Selleck）；

體內(nèi)配方配制方法：取μL DMSO母液，加入μL PEG300，混勻澄清后加入μL Tween 80，混勻澄清后加入μL ddH2O，混勻澄清。

體內(nèi)配方配制方法：取μL DMSO母液，加入μL Corn oil，混勻澄清。

注意：1. 首先保證母液是澄清的；
2.一定要按照順序依次將溶劑加入，進(jìn)行下一步操作之前必須保證上一步操作得到的是澄清的溶液，可采用渦旋、超聲或水浴加熱等物理方法助溶。

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