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。
货号:ajcx39218
CAS:2623158-64-3
分子式:C19H20F3N7
分子量：403.4
溶解度:DMSO : 125 mg/mL (309.87 mM; Need ultrasonic)
纯度：98%
存储：Store at -20°C
库存：现货

Background:

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].

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].

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].

[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.