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

Narazaciclib (ON123300), a strong and brain-penetrant multi-kinase inhibitor, inhibits CDK4 (IC 50 =3.9 nM), Ark5 (IC 50 =5 nM), PDGFRβ (IC 50 =26 nM), FGFR1 (IC 50 =26 nM), RET (IC 50 =9.2 nM), and FYN (IC 50 =11 nM). Single agent Narazaciclib causes a dose-dependent suppression of phosphorylation of Akt as well as activation of Erk in brain tumors. Narazaciclib inhibits CDK6 with an IC 50 of 9.82 nM.

Solid

Cdk4/cyclin D1 3.9 nM (IC50) ARK5 5 nM (IC

Narazaciclib (ON123300) inhibits U87 glioma cell proliferation with an IC50 of 3.4±0.1 μM.Narazaciclib (1 and 10 μM) inhibits cell proliferation in a panel of 11 glioma models including a patient-derived model (GBM10).
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.ON123300 inhibits PI3Kδ with the IC50 of 144nM. has not independently confirmed the accuracy of these methods. They are for reference only.

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 (T 1/2 ) is 1.5 h for 5 mg/kg and 25 mg/kg in plasma. has not independently confirmed the accuracy of these methods. They are for reference only.

Room temperature in continental US; may vary elsewhere.

Powder -20°C 3 years；4°C 2 years

[1]. Hua Lv, et al. Integrated pharmacokinetic-driven approach to screen candidate anticancer drugs for brain tumor chemotherapy. AAPS J. 2013 Jan;15(1):250-7.
[2]. Xiaoping Zhang, et al. Preclinical pharmacological evaluation of a novel multiple kinase inhibitor, ON123300, in brain tumor models. Mol Cancer Ther. 2014 May;13(5):1105-16.

In Vitro: DMSO : 16.67 mg/mL (38.81 mM; ultrasonic and warming and heat to 60°C)配制储备液