Narazaciclib (ON123300) 是一种强效的，可透过血脑屏障的多激酶抑制剂，可抑制CDK4(IC50=3.9 nM），Ark5(IC50=5 nM)，PDGFRβ(IC50=26 nM)，FGFR1(IC50=26 nM)，RET(IC50=9.2 nM) 和FYN(IC50=11 nM)。Narazaciclib 在脑肿瘤中抑制 Akt 磷酸化及激活 Erk。Narazaciclib 抑制CDK6，IC50为 9.82 nM。
| 生物活性 | Narazaciclib (ON123300), a strong and brain-penetrant[1]multi-kinase inhibitor, inhibitsCDK4(IC50=3.9 nM),Ark5(IC50=5 nM),PDGFRβ(IC50=26 nM),FGFR1(IC50=26 nM),RET(IC50=9.2 nM), andFYN(IC50=11 nM). Single agent Narazaciclib causes a dose-dependent suppression of phosphorylation ofAktas well as activation ofErkin brain tumors[2]. Narazaciclib inhibitsCDK6with anIC50of 9.82 nM[3]. |
| IC50& Target[2][3] | Cdk4/cyclin D1 3.9 nM (IC50) | ARK5 5 nM (IC50) | CDK6/cyclinD1 9.82 nM (IC50) | RET 9.2 nM (IC50) | FYN 11 nM (IC50) | FGFR1 26 nM (IC50) | PDGFRβ 26 nM (IC50) | PI3K-δ 144 nM (IC50) |
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体外研究
(In Vitro) | Narazaciclib (ON123300) inhibits U87 glioma cell proliferation with an IC50of 3.4±0.1 μM[2].
Narazaciclib (1 and 10 μM) inhibits cell proliferation in a panel of 11 glioma models including a patient-derived model (GBM10)[2].
Narazaciclib (6.3 μM; 1 h) reduces phosphorylation of Akt and its downstream signaling components, P70S6K, 40S rpS6 and Rb S780, yet ON123300 induces Erk activation in U87 cells; both in a dose- and time-dependent manner[2].
ON123300 inhibits PI3Kδ with the IC50of 144nM[3].
Cell Cytotoxicity Assay[2] | Cell Line: | U87 glioma cells | | Concentration: | 0, 4, 8, 12, 16 μM | | Incubation Time: | 72 hour | | Result: | Had an IC50equal to 3.4±0.1 μM. |
Western Blot Analysis[2] | Cell Line: | U87 cells | | Concentration: | 6.3 μM | | Incubation Time: | 1 h | | Result: | Inhibited phosphorylation of Akt (at S473 site) and its downstream signaling components, P70S6K, 40S ribosomal protein S6 (rpS6) and Rb S780 (decreased to 40.1%; 31.8 %; 60.5%; 54.5% relatively to control), yet increased p-Erk (increased to 120% relative to control). |
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体内研究
(In Vivo) | Narazaciclib (ON123300) decreases p-Akt expression and increases p-Erk activity in brain tumors upon administration at both IV doses of 5 mg/kg and 25 mg/kg in U87 brain tumor-bearing mouse. The half-life (T1/2) is 1.5 h for 5 mg/kg and 25 mg/kg in plasma[2].
| Animal Model: | NIH Swiss nude mice bearing U87 glioma model[2]. | | Dosage: | 5 mg/kg or 25 mg/kg | | Administration: | IV bolus at a dose of either 5 mg/kg or 25 mg/kg via a tail vein. | | Result: | The p-Akt rapidly declined and reached nadir values of 73% and 60% of control within 30 min after 5 mg/kg and 25 mg/kg dose levels, respectively. |
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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 : 16.67 mg/mL(38.81 mM;ultrasonic and warming and heat to 60℃) 配制储备液 | 1 mM | 2.3282 mL | 11.6409 mL | 23.2818 mL | | 5 mM | 0.4656 mL | 2.3282 mL | 4.6564 mL | | 10 mM | 0.2328 mL | 1.1641 mL | 2.3282 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。 |
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