LY 364947
中文名称:
LY 364947
中文同义词:
4-[3-(2-吡啶基)-1H-吡唑-4-基]喹啉 英文名称:LY-364947;4-(3-吡啶-2-基-1H-吡唑-4-基)喹啉;4-[3-(2-吡啶基)-1H-吡唑-4-基]喹啉;TGFΒR-I抑制剂(LY-364947)
英文名称:
LY-364947
英文同义词:
[3-(Pyridin-2-yl)-4-(4-quinonyl)]-1H-pyrazole;4-[3-(2-Pyridinyl)-1H-pyrazol-4-yl]-quinoline;LY364947(HTS 466284);E 616451;HTS 466284;2-[4-(Quinolin-4-yl)-1H-pyrazol-3-yl]pyridine, 3-(Pyridin-2-yl)-4-(quinolin-4-yl)-1H-pyrazole;Quinoline, 4-[3-(2-pyridinyl)-1H-pyrazol-4-yl]-;4-[3-(2-Pyridinyl)-1H-pyrazol-4-yl]quinoline E 616451
CAS号:
396129-53-6
分子式:
C17H12N4
分子量:
272.3
EINECS号:
相关类别:
小分子抑制剂;小分子抑制剂，天然产物;细胞生物学试剂;API;Inhibitors;Smad;TGF-beta
Mol文件:
396129-53-6.mol
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
InChIKey
IBCXZJCWDGCXQT-UHFFFAOYSA-N
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
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。
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
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