Clathrin-IN-1

Clathrin-IN-1 is a selective clathrin-mediated endocytosis (CME) inhibitor. Clathrin-IN-1 selectively inhibits amphiphysin association of clathrin terminal domain (TD) with an IC50 value of 12 μM. Clathrin-IN-1 acutely interferes with receptor-mediated endocytosis, entry of HIV, and synaptic vesicle recycling.

Preincubation of HeLa cells with Clathrin-IN-1 (Pitstops 2) leads to a dose-dependent inhibition of Tf uptake with an IC₅₀ value (12-5 μM). Application of 30 μM Clathrin-IN-1 completely blocked Tf endocytosis. Clathrin-IN-1-induced block of Tf endocytosis in HeLa cells was completely reversed within 1-3 hr of drug washout. In U2OS cells, the IC₅₀ for Tf uptake is 9.7 μM. Pitstop 2 also causes a potent inhibition of EGF uptake^[1].
Clathrin-IN-1 (Pitstops 2) potently and specifically reduced HIV-1 infectivity by >90% in HeLa cells^[1].
Pitstop-induced inhibition of clathrin TD function acutely interferes with receptor-mediated endocytosis, entry of HIV, and synaptic vesicle recycling. Endocytosis inhibition is caused by a dramatic increase in the lifetimes of clathrin coat components, including FCHo, clathrin, and dynamin, suggesting that the clathrin TD regulates coated pit dynamics^[1].

References:
[1]. Lisa von Kleist, et al. Role of the clathrin terminal domain in regulating coated pit dynamics revealed by small molecule inhibition. Cell. 2011 Aug 5;146(3):471-84.