Crenigacestat (LY3039478)

目錄號：S7169 Purity: 99.89%

Crenigacestat (LY3039478) 是一種有效的Notch和 gamma-secretase 的抑制劑，其對Notch的IC50值為0.41 nM。

Crenigacestat (LY3039478) Chemical Structure

CAS: 1421438-81-4

規(guī)格	價格	庫存
10mM (1mL in DMSO)	2121.21	現(xiàn)貨
5mg	1417.68	現(xiàn)貨
25mg	4677.69	現(xiàn)貨
1g	57330	現(xiàn)貨
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產(chǎn)品質(zhì)控

批次：純度： 99.89%

99.89

Crenigacestat (LY3039478)相關(guān)產(chǎn)品

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相關(guān)化合物庫	激酶抑制劑庫 FDA藥物庫干細胞小分子化合物庫 GPCR小分子化合物庫干細胞分化化合物庫	點擊展開

細胞實驗數(shù)據(jù)示例

細胞系	實驗類型	孵育時間	活性描述	文獻信息(PMID)
MOLT-4	Function assay	24 hrs	Inhibition of gamma-secretase mediated cleavage of Notch 1 in human MOLT-4 cells assessed as nuclear accumulation of Notch 1 intracellular domain (N1ICD) after 24 hrs by ELISA, IC50 = 0.00074 μM.	24900678
HCT 116	Function assay	24 hrs	Inhibition of gamma-secretase mediated cleavage of Notch 1 in human HCT 116 cells assessed as nuclear accumulation of Notch 1 intracellular domain (N1ICD) after 24 hrs by ELISA, IC50 = 0.00072 μM.	24900678
MIAPaCa2	Function assay	24 hrs	Inhibition of gamma-secretase mediated cleavage of Notch 1 in human MIAPaCa2 cells assessed as nuclear accumulation of Notch 1 intracellular domain (N1ICD) after 24 hrs by ELISA, IC50 = 0.00071 μM.	24900678
MOLT-3	Function assay	24 hrs	Inhibition of gamma-secretase mediated cleavage of Notch 1 in human MOLT-3 cells assessed as nuclear accumulation of Notch 1 intracellular domain (N1ICD) after 24 hrs by ELISA, IC50 = 0.00061 μM.	24900678
MDA-MB-231	Function assay	24 hrs	Inhibition of gamma-secretase mediated cleavage of Notch 1 in human MDA-MB-231 cells assessed as nuclear accumulation of Notch 1 intracellular domain (N1ICD) after 24 hrs by ELISA, IC50 = 0.0005 μM.	24900678
A375	Function assay	24 hrs	Inhibition of gamma-secretase mediated cleavage of Notch 1 in human A375 cells assessed as nuclear accumulation of Notch 1 intracellular domain (N1ICD) after 24 hrs by ELISA, IC50 = 0.00048 μM.	24900678
BxPC3	Function assay	24 hrs	Inhibition of gamma-secretase mediated cleavage of Notch 1 in human BxPC3 cells assessed as nuclear accumulation of Notch 1 intracellular domain (N1ICD) after 24 hrs by ELISA, IC50 = 0.00039 μM.	24900678
U-87-MG	Function assay	24 hrs	Inhibition of gamma-secretase mediated cleavage of Notch 1 in human U-87-MG cells assessed as nuclear accumulation of Notch 1 intracellular domain (N1ICD) after 24 hrs by ELISA, IC50 = 0.00028 μM.	24900678
HEL 92.1.7	Function assay	24 hrs	Inhibition of gamma-secretase mediated cleavage of Notch 1 in human HEL 92.1.7 cells assessed as nuclear accumulation of Notch 1 intracellular domain (N1ICD) after 24 hrs by ELISA, IC50 = 0.00023 μM.	24900678
SW480	Function assay	24 hrs	Inhibition of gamma-secretase mediated cleavage of Notch 1 in human SW480 cells assessed as nuclear accumulation of Notch 1 intracellular domain (N1ICD) after 24 hrs by ELISA, IC50 = 0.0001 μM.	24900678
K562	Function assay	24 hrs	Inhibition of gamma-secretase mediated cleavage of Notch 1 in human K562 cells assessed as nuclear accumulation of Notch 1 intracellular domain (N1ICD) after 24 hrs by ELISA, IC50 = 0.00074 μM.	24900678
CCRF-CEM	Function assay	24 hrs	Inhibition of gamma-secretase mediated cleavage of Notch 1 in human CCRF-CEM cells assessed as nuclear accumulation of Notch 1 intracellular domain (N1ICD) after 24 hrs by ELISA, IC50 = 0.00076 μM.	24900678
DLD1	Function assay	24 hrs	Inhibition of gamma-secretase mediated cleavage of Notch 1 in human DLD1 cells assessed as nuclear accumulation of Notch 1 intracellular domain (N1ICD) after 24 hrs by ELISA, IC50 = 0.00098 μM.	24900678
A2780	Function assay	24 hrs	Inhibition of gamma-secretase mediated cleavage of Notch 1 in human A2780 cells assessed as nuclear accumulation of Notch 1 intracellular domain (N1ICD) after 24 hrs by ELISA, IC50 = 0.00103 μM.	24900678
SUP-T1	Function assay	24 hrs	Inhibition of gamma-secretase mediated cleavage of Notch 1 in human SUP-T1 cells assessed as nuclear accumulation of Notch 1 intracellular domain (N1ICD) after 24 hrs by ELISA, IC50 = 0.00124 μM.	24900678
Jurkat	Function assay	24 hrs	Inhibition of gamma-secretase mediated cleavage of Notch 1 in human Jurkat cells assessed as nuclear accumulation of Notch 1 intracellular domain (N1ICD) after 24 hrs by ELISA, IC50 = 0.00595 μM.	24900678
HEK293deltaE12	Function assay		Inhibition of gamma-secretase mediated cleavage of transfected mouse Notch 1 (1703-2183) harboring N-terminal 23 aminoacid signal peptide sequence in human HEK293deltaE12 cells assessed as nuclear accumulation of Notch 1 intracellular domain (N1ICD) after, IC50 = 0.00041 μM.	24900678
點擊查看更多細胞系數(shù)據(jù)

生物活性

產(chǎn)品描述

Crenigacestat (LY3039478) 是一種有效的Notch和 gamma-secretase 的抑制劑，其對Notch的IC50值為0.41 nM。

靶點

Notch ^[1]

~1 nM

體外研究(In Vitro)
體外研究活性	LY3039478是一種Notch-1胞內(nèi)區(qū)域剪切的有效抑制劑，在大多數(shù)所檢測的腫瘤細胞中IC50中約為1 nM。LY3039478也有效地抑制突變型Notch受體活性^[2]。LY3039478可顯著地抑制兩種腎透明細胞癌細胞的生長。其處理可減少Myc和cyclin A1的表達，引起透明細胞癌細胞在G0/G1期的細胞阻滯^[3]。
細胞實驗	細胞系	K07074細胞
	濃度	100 nM
	孵育時間	24, 48, 72, 96 h
	方法	將K07074細胞以10⁵ cells/孔鋪于24孔板中。接種24小時后，向培養(yǎng)基中加入K0704或DMSO。處理完后，測定細胞活性。

體內(nèi)研究(In Vivo)
體內(nèi)研究活性	在大鼠中，其口服生物利用度為65%，CL=98 mL/min/kg, VDss=4.9 L/kg。在狗中，口服生物利用度為67%，CL=3.8 mL/min/kg, VDss=1.4 L/kg^[1]。在異種移植瘤模型中，LY3039478可在腫瘤微環(huán)境中抑制N1ICD的剪切以及Notch靶基因的表達。在依賴于Notch信號的移植瘤模型中，Notch剪切的抑制誘導(dǎo)了凋亡的產(chǎn)生^[2]。在免疫缺陷NSG攜瘤小鼠（移植769-P CCRCC細胞）中，LY3039478可顯著地提高其生存率、延遲腫瘤生長^[3]。
動物實驗	Animal Models	Mice
	Dosages	8 mg/kg
	Administration	oral gavage

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試驗信息 (data from https://clinicaltrials.gov, updated on 2024-05-22)
NCT02906618	Completed	Healthy	Eli Lilly and Company	October 4 2016	Phase 1
NCT02917733	Completed	Healthy	Eli Lilly and Company	September 2016	Phase 1
NCT02836600	Completed	Advanced Solid Tumor	Eli Lilly and Company	September 9 2016	Phase 1
NCT02518113	Completed	T-cell Acute Lymphoblastic Leukemia\|T-cell Lymphoblastic Lymphoma	Eli Lilly and Company	October 1 2015	Phase 1\|Phase 2

參考文獻
http://www.rsc.org/images/Warren_Porter_tcm18-237088.pdf http://cancerres.aacrjournals.org/content/73/8_Supplement/1131.short https://pubmed.ncbi.nlm.nih.gov/27909050/ https://pubmed.ncbi.nlm.nih.gov/27103434/ + 展開

參考文獻

http://www.rsc.org/images/Warren_Porter_tcm18-237088.pdf
http://cancerres.aacrjournals.org/content/73/8_Supplement/1131.short
https://pubmed.ncbi.nlm.nih.gov/27909050/

https://pubmed.ncbi.nlm.nih.gov/27103434/

+ 展開

化學(xué)信息&溶解度

分子量	464.44	分子式	C₂₂H₂₃F₃N₄O₄
CAS號	1421438-81-4	SDF	Download Crenigacestat (LY3039478) SDF
Smiles	CC(C(=O)NC1C2=CC=CC=C2C3=C(N=CC=C3)N(C1=O)CCO)NC(=O)CCC(F)(F)F
儲存條件(自收到貨起)	3年-20°C粉狀	儲備液保存和期限建議分裝儲備液，避免反復(fù)凍融！	1年-80°C溶于溶劑
儲存條件(自收到貨起)	3年-20°C粉狀	儲備液保存和期限建議分裝儲備液，避免反復(fù)凍融！	1個月-20°C溶于溶劑

體外溶解度
批次：

DMSO : 93 mg/mL ( (200.24 mM) ；DMSO吸濕會降低化合物溶解度，請使用新開封DMSO)

Ethanol : 93 mg/mL (200.24 mM)

Water : Insoluble

DMSO : 92 mg/mL ( (198.08 mM) ；DMSO吸濕會降低化合物溶解度，請使用新開封DMSO)

Ethanol : 92 mg/mL (198.08 mM)

Water : Insoluble

DMSO : 93 mg/mL ( (200.24 mM) ；DMSO吸濕會降低化合物溶解度，請使用新開封DMSO)

Ethanol : 93 mg/mL (200.24 mM)

Water : Insoluble

摩爾濃度計算器

體內(nèi)溶解配方批次：現(xiàn)配現(xiàn)用，請按從左到右的順序依次添加，澄清后再加入下一溶劑				動物體內(nèi)配方計算器
均勻懸濁液	CMC-NA	≥5mg/ml	以 1 mL 工作液為例，取 5 mg該產(chǎn)品加到 1 ml CMC-NA 溶液中，混合均勻，即可得工作液濃度為 5 mg/ml的均勻懸濁液。
均勻懸濁液	CMC-NA	≥5mg/ml	以 1 mL 工作液為例，取 5 mg該產(chǎn)品加到 1 ml CMC-NA 溶液中，混合均勻，即可得工作液濃度為 5 mg/ml的均勻懸濁液。
均勻懸濁液	CMC-NA	≥5mg/ml	以 1 mL 工作液為例，取 5 mg該產(chǎn)品加到 1 ml CMC-NA 溶液中，混合均勻，即可得工作液濃度為 5 mg/ml的均勻懸濁液。
澄清溶液	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O 該配方已經(jīng)過Selleck實驗室實測。如果上述溶解方案不能滿足您的需求，可聯(lián)系Selleck銷售提供定制化測試。	9.500mg/ml (20.45mM)	以 1 mL 工作液為例，取50μL190mg/ml的澄清DMSO儲備液加到400μL PEG300中，混合均勻使其澄清；向上述體系中加入50μLTween80，混合均勻使其澄清；然后繼續(xù)加入500μL ddH2O定容至 1 mL。工作液請現(xiàn)配現(xiàn)用！

實驗計算

摩爾濃度計算器

質(zhì)量	濃度	體積	分子量
=	×	×

稀釋計算器分子量計算器

動物體內(nèi)配方計算器（澄清溶液）

第一步：請輸入基本實驗信息（考慮到實驗過程中的損耗，建議多配一只動物的藥量）

給藥劑量 mg/kg 動物平均體重 g 每只動物給藥體積 μL 動物數(shù)量只

第二步：請輸入動物體內(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，請聯(lián)系Selleck為您提供正確的澄清溶液配方）

% DMSO + % + % Tween 80 + % ddH2O

%DMSO+ %

計算結(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：如該濃度超過該批次藥物DMSO溶解度，請先聯(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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