您好,欢迎来到试剂信息网! [登录] [免费注册]
试剂信息网
位置:首页 > 产品库 > Galunisertib(LY2157299)
立即咨询
咨询类型:
     
*姓名:
*电话:
*单位:
Email:
*留言内容:
请详细说明您的需求。
*验证码:
 
Galunisertib(LY2157299)
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。
Galunisertib(LY2157299)图片
CAS NO:700874-72-2
规格:≥98%
包装与价格:
包装价格(元)
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议
1g电议

产品介绍
理化性质和储存条件
Molecular Weight (MW)369.42
FormulaC22H19N5O
CAS No.700874-72-2 (free);
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 74 mg/mL (200.3 mM)
Water: <1 mg/mL
Ethanol:<1 mg/mL
Solubility (In vivo)2% DMSO+30% PEG 300+ddH2O: 5 mg/mL
Synonyms

LY2157299; LY2157299; LY 2157299

SMILES Code: O=C(C1=CC=C2N=CC=C(C3=C(CCC4)N4N=C3C5=NC(C)=CC=C5)C2=C1)N

Chemical Name: 4-(2-(6-methylpyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)quinoline-6-carboxamide

实验参考方法
In Vitro

In vitro activity: LY2157299 (also known as Galunisertib) potently inhibits the TGFβ receptor signaling. LY2157299 abolishes the TGFβ induced Smad2 phosphorylation in HUVEC cells. LY2157299 also shows dose dependent potentiation of VEGF or bFGF induced cell proliferation in HUVEC. LY2157299 also promotes VEGF induced HUVEC cell migration. LY2157299 potentiates angiogenesis in the in vitro VEGF-stimulated cord formation assay. Y2157299 inhibits TGF-β-mediated SMAD2 activation and hematopoietic suppression in primary hematopoietic stem cells in a dose-dependent manner. LY2157199 treatment stimulates hematopoiesis from primary MDS bone marrow specimens. In human glioblastoma (GBM) cells, LY2157299 treatment blocks signaling through the heteromeric TGFβ receptor complex to reduce levels of active, phosphorylated SMAD.


Kinase Assay: LY2157299 (also known as Galunisertib) is a potent, selective ATP-mimetic inhibitor of TGF-β receptor (TβR)-I activation LY2157299 (0.1, 1, 10, and 100 μM) displays a slight dose-dependent potentiation of Sorafenib in SK-Sora, HepG2, and Hep3B cell lines but not in JHH6, SK-HEP1, and HuH7 cell lines.


Cell Assay: Cell survival is determined using the MTT assay. The conversion of yellow water-soluble tetrazolium MTT into purple insoluble formazan is catalyzed by mitochondrial dehydrogenases and used to estimate the number of viable cells. In brief, cells are seeded in 96-well tissue culture plates at a density of 2×103 cells/well. After drug exposure, cells are incubated with 0.4 mg/mL MTT for 4 hours at 37°C. After incubation, the supernatant is discarded, insoluble formazan precipitates are dissolved in 0.1 mL of DMSO, and the absorbance is measured at 560 nm by use of a microplate reader. Wells with untreated cells or with drug-containing medium without cells are used as positive and negative controls respectively. For proliferation assay, MTT assay is done daily to determine the number of viable cells in untreated control and LY2157299 (0.1, 1, 10, and 10 μM)-treated group.

In VivoAlthough anti-tumor activity has been observed in several pre-clinical models, LY2157299 fails to show significant in vivo angiogenic effects in the 4T1, Colo205, or A549 xenograft models. Administration of LY2157299 ameliorates anemia in a TGF-β overexpressing transgenic mouse model of bone marrow failure. Oral administration of LY2157299 at 75 mg/kg/day displays significant antitumor activity against both Calu6 and MX1 xenografts in mice. In vivo, LY2157299 induces angiogenesis and enhances VEGF and basic-fibroblast-growth-factor-induced angiogenesis in a Matrigel-plug assay, whereas adding an alpha5-integrin-neutralizing antibody to the Matrigel selectively inhibits this enhanced response.
Animal modelNude mice implanted subcutaneously with Calu6 or MX1 cells
Formulation & DosageDissolved in DMSO and diluted in saline; 75 mg/kg/day; oral gavage
ReferencesCancer Res. 2011 Feb 1;71(3):955-63.