GNF-2 is a highly selective, allosteric, non-ATP competitive inhibitor of Bcr-Abl. GNF-2 inhibits Ba/F3.p210 proliferation with an IC50 of 138 nM .
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 IC50 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 IC50 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 (IC50 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 IC50 of 267 nM.
Increased number of Ba/F3.p210 cells undergoing apoptosis at 1 μM for 48 h.
Ba/F3.p210 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 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 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.
分子式
C18H13F3N4O2
分子量
374.32
CAS号
778270-11-4
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Powder
-20°C
3 years
4°C
2 years
In solvent
-80°C
6 months
-20°C
1 month
溶解性数据
In Vitro:
DMSO : ≥ 100 mg/mL (267.15 mM)
H2O : < 0.1 mg/mL (ultrasonic;warming;heat to 60°C) (insoluble)