PCC0208017

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

PCC0208017 是有效的微管亲和力调节激酶 MARK3/MARK4 抑制剂，IC50 值分别为 1.8 和 2.01 nM。 PCC0208017 对 MARK1 和 MARK2 的抑制活性要低得多，IC50 值分别为 31.4 和 33.7 nM。 PCC0208017 在体内外都抑制神经胶质瘤进展。PCC0208017 破坏微管动力学并诱导 G2/M 期细胞周期停滞和细胞凋亡。PCC0208017 具有强大的抗肿瘤活性并显示出良好的 BBB 通透性。

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.

PCC0208017 inhibits the activity of MARK3 and MARK4 and decreased the phosphorylation of Tau.PCC0208017 (1-5 μM; 24?hours) treatment results in decreased phosphorylation of Tau, the subtract of MARKs. PCC0208017 (3-21 μM; 24?hours) suppresses the proliferation of glioma cells.Cell Proliferation Assay 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 Cell Line: Concentration:Glioma cell lines GL261 and U2511, 2, 5 μM Incubation Time:24?hours Result:Decreased the phosphorylation of Tau.

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).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.Animal Model:C57BL/6 mice bearing murine glioma GL261?xenograft tumor Dosage: 50?mg/kg and 100?mg/kg (suspended in a 0.5% methylcellulose solution).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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Apoptosis

Apoptosis

Apoptosis

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2623158-64-3

403.4

C19H20F3N7

>98% (HPLC)

In Vitro:?DMSO 中的溶解度 : 125 mg/mL (309.87 mM; 超声助溶 )

CN1CCc2cc(Nc3ncc(c(NCc4cc[nH]n4)n3)C(F)(F)F)ccc2C1

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(-20℃)

With Ice Pack

≥ 2 years