GNF-7
GNF-7 性质
| 密度 | 1.404±0.06 g/cm3(Predicted) |
|---|---|
| 储存条件 | Store at -20°C |
| 溶解度 | 不溶于乙醇；不溶于水； DMSO 中≥5.48 mg/mL |
| 形态 | 固体 |
| 酸度系数(pKa) | 12.82±0.70(Predicted) |
GNF-7 用途与合成方法
IC50: 133 nM (Bcr-Abl WT ), 61 nM (Bcr-Abl T315I ), 25 nM (ACK1), 8 nM (GCK)
GNF-7 potently inhibits wild-type Bcr-Abl (IC
50
<5 nM) and Bcr-Abl mutants such as T315I (IC
50
=11 nM), G250E (IC
50
<5 nM), E255V (IC
50
=10 nM), F317L (IC
50
<5 nM) and M351T (IC
50
<5 nM) in cellular assays.
GNF-7 (1 μM; 2 hours) suppresses AKT/mTOR signaling and GCK downstream.
GNF-7 (1 μM; 24 hours) induces of apoptosis and cell cycle arrest in NRAS mutant cell lines.
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. |
GNF-7 (10-20 mg/kg; o.p.; daily; for 7 days) displays significant in vivo efficacy against T315I Bcr-Abl in the bioluminescent xenograft mouse model.
GNF-7 exhibits moderate oral bioavailability (mice 36%) and C
max
(mice 3616 nM) following oral administration (mice 20 mg/kg).
GNF-7 exhibits terminal elimination half-lives (mice 3.8 h) due to high plasma clearance (8.6 mL/min/kg) following intravenous injection (mice 5 mg/kg).
| 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%), C max (3616 nM), T 1/2 (3.2 h). |
GNF-7 价格(试剂级)
| 更新日期 | 产品编号 | 产品名称 | CAS号 | 包装 | 价格 |
|---|---|---|---|---|---|
| 2024-01-25 | HY-10943 | 1 mg | 490 | ||
| 2024-01-25 | HY-10943 | GNF-7 | 839706-07-9 | 5mg | 1080 |
