GNF-7

SKU: orb1223895

Description

A potent and selective type-II kinase inhibitor of Bcr-Abl; inhibits wt Bcr-Abl/T315I Bcr-Abl (IC50< 5 nM) and Bcr-Abl mutants such as G250E, Q252H, Y253H, E255K, E255V, F317L, and M351T in biochemical and cellular assays; displays in vivo efficacy against T315I-Bcr-Abl in xenograft mouse model.

Key Properties

• CAS Number: 839706-07-9
• MW: 547.5311
• Purity: >98% (HPLC)
• Formula: C₂₈H₂₄F₃N₇O₂
• SMILES: O=C(NC1=CC=C(C)C(N2CC3=CN=C(NC4=CC=C(C)N=C4)N=C3N(C)C2=O)=C1)C5=CC=CC(C(F)(F)F)=C5
• Target: Bcr-Abl
• Solubility: DMSO: ≥ 33 mg/mL

Bioactivity

• In Vivo:
  Animal model: 6-8 weeks old SCID beige female mice, with Ba/F3-T315I-Bcr-Abl cells xenograft. Dosage: 10 mg/kg, 20 mg/kg. Administration: Oral administration, daily, for 7 days. Result: Effectively inhibited tumor growth of T315I-Bcr-Abl-Ba/F3 cells in mice at low doses (10 mg/kg). Animal model: 5-6 weeks old male Balb/c mice (20-25 g). Dosage: 5 mg/kg for i. v. ; 20 mg/kg for i. g. (Pharmacokinetic Analysis). Administration: Intravenous injection and oral gavage. Result: Oral bioavailability (36%), Cmax (3616 nM), T1/2 (3.2 h).
• In Vitro:
  Western blot analysis. Cell line: Ba/F3-NRAS-G12D cells, OCI-AML3 cells. Concentration: 1 μM. Incubation time: 2 hours. Result: Caused a decreased level of phosphorylation of p70S6K1, AKT (S473), JNK, and p38.Apoptosis Analysis Cell line: OCI-AML3 cells. Concentration: 1 μM. Incubation time: 24 hours. Result: Increased the levels of both cleaved PARP and cleaved caspase 3 and diminished bcl-2 and MCL1.Cell Cycle Analysis Cell line: OCI-AML3 cells. Concentration: 1 μM. Incubation time: 24 hours. Result: Induced of G0-G1 arrest.

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 7 | GNF7

Quick Database Links

Gene Symbol

Bcr-Abl