LY2409881 trihydrochloride

立即咨询

本产品不向个人销售，仅用作科学研究，不用于任何人体实验及非科研性质的动物实验。

CAS NO:	946518-60-1
规格:	≥98%

包装与价格：

包装	价格(元)
5mg	电议
10mg	电议
25mg	电议
50mg	电议
100mg	电议
250mg	电议
500mg	电议

产品介绍

LY2409881 trihydrochloride (LY-2409881; LY 2409881), the trihydrochloride salt of LY-2409881, is a novel, potent and selective IKK2 ( IκB kinase β) inhibitor with potential anticancer and anti-inflammatory activity. It inhibits IKK2 ( IκB kinase β) with an IC50 of 30 nM, and exhibits >10-fold selectivity for inhibiting IKK2 over IKK1 and other closely related kinases. LY2409881 significantly inhibited tumor growth in vivo in SCID-beige xenograft mouse model. LY2409881 potently synergizes with histone deacetylase inhibitors in preclinical models of lymphoma through the downregulation of NF-κB. LY2409881 inhibited constitutively activated NF-κB, and caused concentration- and time-dependent growth inhibition and apoptosis in lymphoma cells. LY2409881 suppressed the activity of the NF-κB subunit p65 in lymphoma cells treated by the HDAC inhibitor romidepsin, underlying a potential mechanism of the marked synergy observed of these two drugs.

理化性质和储存条件

Molecular Weight (MW)	594.43
Formula	C24H32Cl4N6OS
CAS No.	946518-60-1 (3HCl);
Storage	-20℃ for 3 years in powder form
Storage	-80℃ for 2 years in solvent
Solubility (In vitro)	DMSO: 20 mg/mL (33.6 mM)
	Water:<1 mg/mL
	Ethanol:<1 mg/mL
Solubility (In vivo)	2% DMSO+30% PEG 300+5% Tween 80+ddH2O: 5 mg/mL
Synonyms	LY2409881 tri-HCl; LY-2409881; LY 2409881; LY2409881 trihydrochloride Chemical Name: 2-(5-chloro-2-((3-(4-methylpiperazin-1-yl)propyl)amino)pyrimidin-4-yl)-N-cyclopropylbenzo[b]thiophene-4-carboxamide trihydrochloride InChi Key: IEXCRLAGBWKVPW-UHFFFAOYSA-N InChi Code: InChI=1S/C24H29ClN6OS.3ClH/c1-30-10-12-31(13-11-30)9-3-8-26-24-27-15-19(25)22(29-24)21-14-18-17(4-2-5-20(18)33-21)23(32)28-16-6-7-16;;;/h2,4-5,14-16H,3,6-13H2,1H3,(H,28,32)(H,26,27,29);3*1H SMILES Code: O=C(C1=C(C=C(C2=NC(NCCCN3CCN(C)CC3)=NC=C2Cl)S4)C4=CC=C1)NC5CC5.[H]Cl.[H]Cl.[H]Cl

实验参考方法

In Vitro	In vitro activity: LY2409881 inhibits constitutively activated NF-KB, and causes concentration- and time-dependent growth inhibition and apoptosis in diffuse large B-cell lymphoma (DLBCL) cells. In the ovarian cancer cell line SKOV3, LY2409881 demonstrates moderate cytotoxicity. LY2409881 is synergistic with doxorubicin and cyclophosphamide in SUDHL2 cell in inhibiting the cell growth, but not in LY1 cell. In both SUDHL2 and LY1 cells, LY2409881 is synergistic with the histone deacetylase (HDAC) inhibitor romidepsin in inhibiting the cell growth. Kinase Assay: LY2409881 is an IKK2 inhibitor that inhibits TNFα-induced activation of NF-κB. By in vitro kinase assay, LY2409881 potently inhibits IKK2, with an IC50 of 30 nM. In contrast, the IC50 for IKK1 and other common kinases is at least one log higher. The specificity of LY2409881 for NF-κB signaling is further studied in a cell-based assay, by examining the effect of LY2409881 in the TNFα-dependent antiapoptosis function. TNFα is a well-characterized upstream stimulus of NF-κB. Cell Assay: Cytotoxicity is evaluated using the CellTiter-Glo Reagent according to the manufacturer's manual. Experiments are carried out in 96-well plates, with each treatment in triplicate. Samples are taken at typically 24, 48, and 72 hours after treatment. Cytotoxicity is expressed by the decreasing percentage of live cells in each treatment relative to the untreated control from the same experiment. IC50 for each cell line is calculated using the CalcuSyn Version 2.0 software.
In Vivo	In SCID-beige xenograft mouse model, LY2409881 (50, 100, and 200 mg/kg, i.p.) significantly inhibits the tumor growth
Animal model	In SCID-beige mice bearing LY10 cell-derived tumors
Formulation & Dosage	50, 100 and 200 mg/kg
References	Clin Cancer Res. 2015 Jan 1;21(1):134-45