ON 123300 is multikinase inhibitor with 3.87, 9.82, 4.95, 26, 26 and 144nM for Cdk4/cyclin D1, CDK6/cyclinD1, ARK5, FGFR1, PDGFRβ and PI3K-δ, respectively. ON 123300 exhibited potent activity against mantle cell lymphomas Z138C and GRANTA 519 with GI50 values of 25nM and 35nM, respectively, as well as inhibited the proliferation of cell lines of different tumor types with GI50 values ranging in 0.1-0.6μM. As a dual inhibitor of both Cdk4/6 and PI3K-δ, ON123300 inhibited phosphorylation of both Rb family proteins and proteins associated with the PI3K/AKT pathway, at concentration of 2.5-10μM post 24h, with apoptosis observed. Treatment of ibrutinib-sensitive and -resistant patient-derived MCLs with ON123300 also triggered apoptosis and inhibition of the Rb and PI3K/AKT pathways. Administration of ON 123300 at dose of 100mg/kg, i.p., daily for 2 weeks significantly inhibited tumor growth in a nude mouse model of Z138C MCL.
UCPH-101 细胞实验
Cell Line
Concentration
Treated Time
Description
References
HEK293 cells
0.34 µM
6 minutes
Investigate the inhibitory effect of UCPH-101 on EAAT1
J Neurosci. 2013 Jan 16;33(3):1068-87
Cortical pyramidal neurons (CPNs)
10 µM
15-18 minutes
To evaluate the effect of GLAST inhibitor on the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) in CPNs. Results showed that UCPH-101 did not significantly alter sEPSC frequency.
CNS Neurosci Ther. 2019 Apr;25(4):509-518
Astrocyte-microglia-neuron mixed culture
0.1 to 10 µM
24 hours
To evaluate the effect of UCPH-101 on L-glutamate uptake, it was found that UCPH-101 inhibited L-glutamate uptake in a concentration-dependent manner.
J Neuroinflammation. 2012 Dec 23;9:275
HEK293T cells
200 µM
5 minutes
To study the inhibitory effect of UCPH-101 on ASCT2, finding that it partially inhibits ASCT2's amino acid uptake activity.
Elife. 2023 Mar 1;12:e83464
HEK293 cells
2 µM to 100 µM
several seconds to minutes
To investigate the non-competitive inhibitory mechanism of UCPH-101 on EAAT1, confirming that it inhibits EAAT1 activity by slowing substrate translocation rather than substrate or Na+ binding.
Elife. 2023 Mar 1;12:e83464
UCPH-101 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Male mice
Fear conditioning model
Bilateral BLA injection
10 nmol/μl
Single injection, 30 minutes before training
Inhibition of EAAT1 activity impaired long-term fear memory formation
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