Pitstop2 is a clathrin inhibitor that inhibits amphoteric binding of clathrin terminal domains with an IC50 value of 12μM[1-2].
In Hela cells, Pitstop2 (5-30µM) inhibits clathrin-independent endocytosis in a dose-dependent manner. In BEAS-2B and COS-7 cells, Pitstop2 (20μM) inhibits the uptake of transferrin and major histocompatibility complex class I (MHCI) proteins[3]. Pitstop2 inhibits gridin-mediated transferrin uptake in HeLa and U2OS cells with IC50 values of 12-15μM and 9.7μM, respectively [1].
Pitstop2 (10µg/kg) pretreatment can partially prevent nitroglycerin (NTG)-induced hyperalgesia in rat chronic migraine (CM) model. Compared with NTG+ vehicle group, Pitstop2 can significantly reduce the expression of CGRP and c-Fos in trigeminal ganglion (TG) and reduce the activation of trigeminovascular system (TVS) in CM rats [4].
References:
[1] von Kleist, L., Stahlschmidt, W., Bulut, H., et al. Role of the clathrin terminal domain in regulating coated pit dynamics revealed by small molecule inhibition. Cell 146(3), 471-484 (2012).
[2] Smith CM, Haucke V, McCluskey A, Robinson PJ, Chircop M. Inhibition of clathrin by pitstop 2 activates the spindle assembly checkpoint and induces cell death in dividing HeLa cancer cells. Mol Cancer. 2013 Jan 17;12:4.
[3] Dutta D, Williamson C D, Cole N B, et al. Pitstop 2 is a potent inhibitor of clathrin-independent endocytosis[J]. 2012.
[4] Zhang L, Zhou Y, Wang Y, Yang L, Wang Y, Shan Z, Liang J, Xiao Z. Inhibiting PAC1 receptor internalization and endosomal ERK pathway activation may ameliorate hyperalgesia in a chronic migraine rat model. Cephalalgia. 2023 Apr;43(4):3331024231163131.
Pitstop2是一种网格蛋白抑制剂，可抑制网格蛋白末端结构域的两性结合，IC50值为12μM[1-2]。
在Hela细胞中，Pitstop2（5-30µM）以剂量依赖性方式抑制网格蛋白独立的内吞作用。在BEAS-2B和COS-7细胞中，Pitstop2（20μM）可抑制转铁蛋白和主要组织相容性复合物I类蛋白（MHCI）的摄取[3]。Pitstop2可抑制HeLa和U2OS细胞中网格蛋白介导的转铁蛋白摄取，IC50值分别为12-15μM和9.7μM[1]。
在大鼠慢性偏头痛（CM）模型中，Pitstop2（10µg/kg）预处理可部分预防硝酸甘油（NTG）诱导的痛觉过敏，与NTG+载体组相比，Pitstop2可以显著降低三叉神经节（TG）中CGRP、c-Fos的表达，减轻CM大鼠的三叉神经血管系统（TVS）激活[4]。