| Description |
PCC0208017 is a microtubule affinity regulating kinases (MARK3/MARK4) inhibitor with IC50s of 1.8 and 2.01 nM, respectively. PCC0208017 has much lower inhibitory activity against MARK1 and MARK2, with IC50s of 31.4 and 33.7 nM, respectively. PCC0208017 suppresses glioma progression in vitro and in vivo. PCC0208017 disrupts microtubule dynamics and induces G2/M phase cell cycle arrest and cell apoptosis. PCC0208017 demonstrates robust antitumor activity in vivo and displays good BBB permeability[1].
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| Related Catalog |
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| In Vitro |
PCC0208017 inhibits the activity of MARK3 and MARK4 and decreased the phosphorylation of Tau[1]. PCC0208017 (1-5 μM; 24 hours) treatment results in decreased phosphorylation of Tau, the subtract of MARKs[1]. PCC0208017 (3-21 μM; 24 hours) suppresses the proliferation of glioma cells[1]. Cell Proliferation Assay[1] Cell Line: The glioma cell lines GL261, U87-MG, U251 Concentration: 0, 3, 6, 9, 12, 15, 18, 21 μM Incubation Time: 24 hours Result: The IC50 values for GL261, U87-MG and U251 were calculated as 2.77, 4.02 and 4.45 μM, respectively. Cell Proliferation Assay[1] Cell Line: Concentration: Glioma cell lines GL261 and U251 1, 2, 5 μM Incubation Time: 24 hours Result: Decreased the phosphorylation of Tau.
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| In Vivo |
PCC0208017 demonstrates robust antitumor activity in vivo and displays good BBB permeability. PCC0208017 (50 and 100 mg/kg; orally administrated) inhibits the growth of xenograft tumors derived from GL261 cells in a dose-dependent manner. Inhibition rates are 56.15% and 70.32%, respectively. Co-treatment of PCC0208017 at dosage of 50 mg/kg significantly enhances the anti-tumor activity of Temozolomide (TMZ; 100 mg/kg), with an increase in tumor inhibition rates from 34.15% (TMZ only) to 83.5% (TMZ+PCC0208017)[1]. PCC0208017 (after a single oral administration at a dose of 50 mg/kg) could be detected in both plasma and brain following a single oral dose of 50 mg/kg. In plasma, Cmax is 1.36 μg/mL and Tmax is 0.833 h. In brain, Cmax is 0.14 μg/mL and Tmax is 0.833 h[1]. Animal Model: C57BL/6 mice bearing murine glioma GL261 xenograft tumor[1] Dosage: 50 mg/kg and 100 mg/kg (suspended in a 0.5% methylcellulose solution)[1]. Administration: Orally administrated every day at a volume of 10 mL/kg Result: Inhibited GL261 cells growth in xenograft mouse model.
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| References |
[1]. Fangfang Li, et al. PCC0208017, a novel small-molecule inhibitor of MARK3/MARK4, suppresses glioma progression in vitro and in vivo. Acta Pharm Sin B.2020 Feb;10(2):289-300.
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