LY 364947

生物活性体外研究体内研究生物活性靶点体外研究体内研究 LY 364947 试剂级价格

LY 364947

CAS号:396129-53-6
英文名:LY-364947
中文名:LY 364947
CBNumber:CB3972214
分子式:C17H12N4
分子量:272.3
MOL File:396129-53-6.mol

LY 364947化学性质

熔点 :>230℃ (dec.)
沸点 :490.8±45.0 °C(Predicted)
密度 :1.283±0.06 g/cm3(Predicted)
储存条件 :2-8°C
溶解度 :DMSO: soluble2mg/mL, clear
酸度系数(pKa) :8.94±0.50(Predicted)
形态 :powder
颜色 :white to beige
稳定性 :Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 3 months.
InChIKey :IBCXZJCWDGCXQT-UHFFFAOYSA-N

安全信息

危险品标志 :T,N
危险类别码 :25-36/37/38-50/53
安全说明 :26-45-60-61
危险品运输编号 :UN 2811 6.1/PG 3
WGK Germany :3
海关编码 :2933491090

LY 364947性质、用途与生产工艺

生物活性 LY364947是一种有效的，ATP竞争性的TGFβR-I抑制剂，IC50为59 nM，比作用于TGFβR-II选择性高7倍。
体外研究 LY364947 is an ATP competitive and tight-binding inhibitor, inhibiting phosphorylation of P-Smad3 by TGFβR-I kinase with Ki of 28 nM. LY364947 inhibits in vivo Smad2 phosphorylation within the NMuMg cells with IC50 of 135 nM. LY364947 reverses TGF-β-mediated growth inhibition in NMuMg cells with IC50 of 0.218 μM. LY364947 potentiates the xVent2-lux BMP4 response in NMuMg cells by 30% at concentrations as low as 0.25 μM. LY364947 (2 μM) prevents TGF-β-induced epithelial−mesenchymal transition in NMuMg cells. LY364947 (3 μM) induces expression of Prox1 and LYVE-1 in almost all HDLECs after 24 hours. LY364947 promotes nuclear export of Foxo3a, with low Smad2/3 and high Akt phosphorylation levels in leukaemia-initiating cells. LY364947 (< 20 μM) suppresses leukaemia-initiating cells colony-forming ability after co-culture with OP-9 stromal cells.
体内研究 LY364947 (1 mg/kg i.p.) accelerates lymphangiogenesis, as evidence by significantly increased the LYVE-1-positive areas, in a mouse model of chronic peritonitis. LY364947 (1 mg/kg i.p.) significantly increases the LYVE-1-positive areas in tumor tissues in tumor xenograft models using BxPC3 pancreatic adenocarcinoma cells. LY364947 (25 mg /kg) increases p-Akt and decreases nuclear Foxo3a in leukaemia-initiating cells in CML-affected mice.
生物活性 LY364947 (HTS 466284)是一种有效的ATP竞争性TGFβR-I抑制剂，无细胞试验中IC50为59 nM，比作用于TGFβR-II选择性高7倍。

靶点

Target	Value
TGFβRI (Cell-free assay)	59 nM
RIPK2 (Cell-free assay)	0.11 μM
CK1δ (Cell-free assay)	0.22 μM
TGFβRII (Cell-free assay)	0.4 μM
MLK-7K (Cell-free assay)	1.4 μM

体外研究
LY364947是一种ATP竞争性，紧密结合抑制剂，通过TGFβR-I激酶抑制P-Smad3磷酸化，Ki为28 nM。LY364947抑制体内Smad2磷酸化，NMuMg细胞中IC50 为135 nM。LY364947逆转NMuMg细胞中TGF-β介导的生长抑制，IC50为0.218 μM。LY364947在0.25 μM的低浓度下，使NMuMg细胞中的xVent2-lux BMP4响应增强30%。LY364947 (2 μM)防止NMuMg 细胞中TGF-β诱导的上皮间叶细胞转化。 LY364947 (3 μM)处理24小时后，几乎在所有HDLECs中诱导Prox1和 LYVE-1表达。 LY364947促进Foxo3a的核输出，在白血病阳性细胞中具有低Smad2/3和高Akt磷酸化水平。与OP-9基质细胞共培养后，LY364947 (< 20 μM)抑制白血病阳性细胞的集落形成能力。
体内研究在慢性腹膜炎小鼠模型中，显著增加的LYVE-1-阳性区域表明，LY364947(1 mg/kg i.p.)加速淋巴管生成。BxPC3胰腺癌细胞的肿瘤异种移植模型中，LY364947 (1 mg/kg i.p.)显著增加肿瘤组织中LYVE-1-阳性区域。在感染CML的小鼠体内白血病阳性细胞中，LY364947 (25 mg /kg)增加p-Akt，并减少细胞核Foxo3a。