ON123300

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

ON123300 是一种有效的多靶点激酶抑制剂，对 ARK5、CDK4、PDGFRβ、FGFR1、RET 和 FYN 的 IC50 分别为 5、3.9、26、26、9.2 和 11 nM。

ON123300 is a potent, multi-targeted kinase inhibitor with IC50 of 5, 3.9, 26, 26, 9.2 and 11 nM for ARK5, CDK4, PDGFRβ, FGFR1, RET and FYN, respectively; inhibits U87 glioma cell proliferation with IC50 3.4 uM, and reduces phosphorylation of Akt, yet it also unexpectedly induces Erk activation and prevents phosphorylation of C-Raf S259; suppresses phosphorylation of Akt as well as activation of Erk in brain tumors in vivo; also exhibits potent activity against mantle cell lymphomas both in vitro and in vivo, triggers apoptosis and inhibition of the Rb and PI3K/AKT pathways.(In Vitro):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.(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.

Cell Cytotoxicity Assay Cell Line:U87 glioma cells Concentration:0, 4, 8, 12, 16 μM Incubation Time:72 hour Result:Had an IC50 equal to 3.4±0.1 μM.Western Blot AnalysisCell 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).

Animal Model:NIH Swiss nude mice bearing U87 glioma model.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.

ON-123300 | ON 123300

Angiogenesis

CDK

CDK

Cancer

——

1357470-29-1

429.5175

C24H27N7O

>98% (HPLC)

10 mM in DMSO

N#CC1=CC2=CN=C(NC3=CC=C(N4CCN(C)CC4)C=C3)N=C2N(C5CCCC5)C1=O

Pyrido[2,3-d]pyrimidine-6-carbonitrile, 8-cyclopentyl-7,8-dihydro-2-[[4-(4-methyl-1-piperazinyl)phenyl]amino]-7-oxo-

(-20℃)

With Ice Pack

≥ 2 years