GNF-2

SKU: orb1224018

Description

A potent, allosteric, non-ATP competitive Bcr-Abl inhibitor that shows exclusive antiproliferative activity toward Bcr-abl-transformed cells; causes growth inhibition of Bcr-Abl positive cell lines with IC50s of 273 nM (K562) and 268 nM (SUP-B15); inhibits mutant Bcr-Abl E255V, Y253H cell growth.

Key Properties

• CAS Number: 778270-11-4
• MW: 374.3166
• Purity: >98% (HPLC)
• Formula: C₁₈H₁₃F₃N₄O₂
• SMILES: O=C(N)C1=CC=CC(C2=NC=NC(NC3=CC=C(OC(F)(F)F)C=C3)=C2)=C1
• Target: Bcr-Abl
• Solubility: DMSO: ≥ 45 mg/mL

Bioactivity

• In Vivo:
  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.
• In Vitro:
  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. Cell Proliferation Assay Cell line: Ba/F3.p210, Ba/F3.p210E255V and Ba/F3.p185Y253H 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.p210E255V 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.p210E255V 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.p210E255V 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.p210E255V cells.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

GNF 2 | GNF2

Quick Database Links

Gene Symbol

Bcr-Abl