GNF-7 是一种多重激酶抑制剂。GNF-7 是Bcr-Abl的抑制剂，对 Bcr-AblWT和 Bcr-AblT315I作用的IC50值分别为 133 nM 和 61 nM。GNF-7 对ACK1和GCK也具有抑制活性，IC50分别为 25 nM 和 8 nM。GNF-7 可用于血液恶性肿瘤的研究。
| 生物活性 | GNF-7 is a multikinase inhibitor. GNF-7 is aBcr-Ablinhibitor, withIC50s of 133 nM and 61 nM forBcr-AblWTandBcr-AblT315I, respectively. GNF-7 also possesses inhibitory activity against bothACK1(activated CDC42 kinase 1) andGCK(germinal center kinase) withIC50s of 25 nM and 8 nM, respectively. GNF-7 can be used for the research of hematologic malignancies[1][2][3]. |
| IC50& Target | IC50: 133 nM (Bcr-AblWT)[1], 61 nM (Bcr-AblT315I)[1], 25 nM (ACK1)[3], 8 nM (GCK)[3] |
体外研究
(In Vitro) | GNF-7 potently inhibits wild-type Bcr-Abl (IC50<5 nm) and bcr-abl mutants such as t315i (ic50=11 nM), G250E (IC50<5 nm), e255v (ic50=10 nM), F317L (IC50<5 nm) and m351t (ic50<5 nm) in cellular assays[2].
GNF-7 (1 μM; 2 hours) suppresses AKT/mTOR signaling and GCK downstream[3].
GNF-7 (1 μM; 24 hours) induces of apoptosis and cell cycle arrest in NRAS mutant cell lines[3].
Western Blot Analysis[3] | 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[3] | 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[3] | Cell Line: | OCI-AML3 cells | | Concentration: | 1 μM | | Incubation Time: | 24 hours | | Result: | Induced of G0-G1 arrest. |
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体内研究
(In Vivo) | 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[2].
GNF-7 exhibits moderate oral bioavailability (mice 36%) and Cmax(mice 3616 nM) following oral administration (mice 20 mg/kg)[2].
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)[2].
| Animal Model: | 6-8 weeks old SCID beige female mice, with Ba/F3-T315I-Bcr-Abl cells xenograft[2] | | 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)[2] | | 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). |
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| 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 |
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| 溶解性数据 | In Vitro: DMSO : ≥ 33 mg/mL(60.27 mM) *"≥" means soluble, but saturation unknown. 配制储备液 | 1 mM | 1.8264 mL | 9.1319 mL | 18.2638 mL | | 5 mM | 0.3653 mL | 1.8264 mL | 3.6528 mL | | 10 mM | 0.1826 mL | 0.9132 mL | 1.8264 mL |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂： ——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；
以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂： 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2 mg/mL (3.65 mM); Clear solution
此方案可获得 ≥ 2 mg/mL (3.65 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 20.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。 2. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 2 mg/mL (3.65 mM); Clear solution
此方案可获得 ≥ 2 mg/mL (3.65 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 20.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。 *以上所有助溶剂都可在本网站选购。
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