3-[6-[[4-(三氟甲氧基)苯基]氨基]-4-嘧啶基]苯甲酰胺

生物活性靶点体外研究体内研究 3-[6-[[4-(三氟甲氧基)苯基]氨基]-4-嘧啶基]苯甲酰胺试剂级价格

CAS号:778270-11-4
英文名:GNF-2
中文名:3-[6-[[4-(三氟甲氧基)苯基]氨基]-4-嘧啶基]苯甲酰胺
CBNumber:CB4973102
分子式:C18H13F3N4O2
分子量:374.32
MOL File:778270-11-4.mol

3-[6-[[4-(三氟甲氧基)苯基]氨基]-4-嘧啶基]苯甲酰胺化学性质

储存条件 :2-8°C
溶解度 :H2O: <2mg/mL
形态 :White solid
颜色 :off-white

安全信息

危险品标志 :Xi
危险类别码 :36/37/38
安全说明 :26
WGK Germany :3

3-[6-[[4-(三氟甲氧基)苯基]氨基]-4-嘧啶基]苯甲酰胺性质、用途与生产工艺

生物活性 GNF-2 是一种具有高度选择性、变构的、非 ATP 竞争性 Bcr-Abl 抑制剂。 GNF-2 抑制 Ba/F3.p210 增殖， IC50 为 138 nM。
靶点

Bcr-Abl

体外研究

GNF-2 selectively inhibits Bcr-abl-dependent cell proliferation. GNF-2 (0.005-10 μM; 48 hours) specifically inhibits the proliferation of the Bcr-abl-expressing cells with an IC ₅₀ of 138 nM and not show any cytotoxic effects on the nontransformed cells at concentrations of up to 10 μM. GNF-2 (0.005-10 μM; 48 hours) causes a dose-dependent growth inhibition of the Bcr-abl-positive cell lines with IC ₅₀ values of 273 nM (K562) and 268 nM (SUP-B15). GNF-2 (0.005-10 μM; 48 hours) inhibits E255V and Y253H mutant Bcr-abl cell growth (IC ₅₀ values of 268 and 194 nM, respectively).
GNF-2 (1-10 μM; 48 hours) induces apoptosis of Bcr-abl-transformed cells.
GNF-2 (0.1-10 μM; 90 minutes) inhibits the cellular tyrosine phosphorylation of Bcr-abl in a dose-dependent manner with an IC ₅₀ of 267 nM.

Cell Proliferation Assay

Cell Line:	Ba/F3.p210, Ba/F3.p210 ^E255V and Ba/F3.p185 ^Y253H cells
Concentration:	0.005, 0.01, 0.1, 1, 10 μM
Incubation Time:	48 hours
Result:	Inhibited Bcr-abl-transformed cells proliferation.

Apoptosis Analysis

Cell Line:	Ba/F3.p210 and Ba/F3.p210 ^E255V cells
Concentration:	1, 10 μM
Incubation Time:	48 hours
Result:	Increased number of Ba/F3.p210 cells undergoing apoptosis at 1 μM for 48 h. Ba/F3.p210 ^E255V underwent apoptotic death after 48 h incubation in the presence of 1 μM or higher concentration.

Western Blot Analysis

Cell Line:	Ba/F3.p210 and Ba/F3.p210 ^E255V cells
Concentration:	0.1, 1, 10 μM
Incubation Time:	90 minutes
Result:	Decreased the autophosphorylation levels at a concentration of 1 μM and were barely detectable at 10 μM, whereas the level of total Bcr-abl remained unchanged. Induced a significant decrease in the levels of p-Stat5 (at Y694) at 1 μM in Ba/F3.p210 and Ba/F3.p210 ^E255V cells.

体内研究

GNF-2 (10 mg/kg; i.p. for 8 days) protects LPS (5 mg/kg) induced bone erosion in mice. GNF-2 protects the LPS induced bone loss and abrogates the LPS-induced decreases of bone volume/tissue volume (BV/TV) of LPS-treated mice.
GNF-2 prevents the LPS-induced increases of N.Oc/B.Pm, the percentage of Oc.S/BS, and the percentage of ES/BS.

Animal Model:	Eight-week-old C57/BL6 mice were administered i.p. injections of LPS (5 mg/kg)
Dosage:	10 mg/kg
Administration:	I.p. injections for 8 days; 1 day before and every day after the LPS injection
Result:	Prevented inflammatory bone destruction in vivo.