endocytosis

Pitstop2 is an amphipathic protein-bound inhibitor of the clathrin terminal domain (IC50=12 μM) with selectivity. Pitstop2 severely interferes with receptor-mediated endocytosis, HIV entry and synaptic vesicle cycling. Pitstop2 has antitumor activity.

Clathrin-IN-1 is a inhibitor of clathrin, and inhibits clathrin-mediated endocytosis (CME) by associating with the terminal domain of clathrin. It has the potential for anti-cancer research.

Hydroxy-Dynasore (Dyngo-4a) , a effective dynamin inhibitor, inhibits withDynI (brain), DynI (rec), and DynII (rec) of IC50 of 0.38 μM, 1.1 μM, and 2.3 μM, respectively.

ES9-17, an analog of ES9 (endosidin9), is an inhibitor of clathrin-mediated endocytosis (CME). ES9-17 inhibits the uptake of FM4-64 and transferrin. ES9-17 inhibits root growth of Arabidopsis seedings.

Ikarugamycin is a macrolide antibiotic discovered in Streptomyces, exhibiting antiprotozoal activity, inducing apoptosis and activating caspases, and also acting as a CME (clathrin-mediated endocytosis) inhibitor.

AAK1-IN-1 (example 123) is an AAK1 (adaptor associated kinase 1) inhibitor with an IC50 of 2.2 nM. AAK1-IN-1 can be used for neurodegenerative diseases research[1]. Adaptor associated kinase 1 (AAK1) is a member of the Arkl/Prkl family of serine/threonine kinases. AAKl mRNA exists in two splice forms termed short and long. The long form predominates and is highly expressed in brain and heart. AAKl is enriched in synaptosomal preparations and is co-localized with endocytic structures in cultured cells. AAKl modulates clatherin coated endocytosis, a process that is important in synaptic vesicle recycling and receptor-mediated endocytosis[1]. [1]. Guanglin Luo, et al. Biaryl kinase inhibitors. WO2015153720A1.

Dynamin IN-2 (compound 43) is a Wiskostatin analogue. Dynamin IN-2 is a potent dynamin inhibitor (dynamin I GTPase, IC50= 1.0 μM). Dynamin IN-2 blocks clathrin mediated endocytosis (CME) (IC50= 9.5 μM).

Dopamine hydrochloride (ASL279) is a natural catecholamine neurotransmitter that mainly acts on dopamine receptors (D1-5 receptors) (EC50=2.7 nM). Dopamine hydrochloride induces VEGFR2 endocytosis through D2 dopamine receptor and has pro-angiogenic activity.

Barbadin is a novel and specific inhibitor of β-arrestin/β2-adaptin interaction with an IC50 value of 19.1 μM for β-arestin1 and 15.6 μM for β-arestin2. Barbadin potentiates the long term effects of lorcaserin on POMC neurons and weight loss. Barbadin potentiates the long-term effects of lorcaserin on POMC neurons and weight loss, blocks agonist-promoted endocytosis of prototypic β2-adrenergic, V2-vasopressin, and angiotensin-II-1 receptors, and may be useful in the study of obesity.

UNI418 is a dual inhibitor targeting PIKfyve and PIP5K1C, exhibiting antiviral activity against SARS-CoV-2 (EC50=1.4 μM). It inhibits the endocytosis of the virus mediated by ACE2 by suppressing PIP5K1C (IC50=60.1 nM; Kd=61 nM). Additionally, UNI418 impedes the entry of SARS-CoV-2 into host cells by inhibiting the proteolytic activation regulated by PIKfyve (Kd=0.78 nM).

AAK1/HDACs-IN-1 (Compound 12) is a dual inhibitor targeting AAK1 and HDACs, effectively inhibiting AAK1, HDAC1, and HDAC6, with IC50 values of 15.9, 148.6, and 5.2 nM, respectively. This compound also hinders SARS-CoV-2 infection by blocking the endocytosis of the ACE2-SARS-CoV-2 complex and the AP2M1-ACE2 interaction.

1-Stearoyl-2-arachidonoyl-sn-glycero-3-phospho-(1'-myo-inositol-3',4'-bisphosphate) ammonium can modulate the activity of the actin network associated with endocytosis.

TIM-098a is a selective AAK1 inhibitor with an IC50 of 0.24 µM. It does not inhibit CaMKK isoforms. By inhibiting AAK1 kinase activity, TIM-098a disrupts AAK1-regulated endocytosis.

IAV-IN-2 (Compound MC-22) inhibits influenza A virus (IAV) by preventing its entry into host cells via clathrin-mediated endocytosis (CME).

BCY17901 TFA is a potent irreversible inhibitor of transferrin receptor 1 (TfR1) with a Ki value of 12 nM. It disrupts TfR1-mediated endocytosis and iron transport, thereby inhibiting the proliferation of tumor cells reliant on iron metabolism. BCY17901 TFA is applicable in research on solid tumors, such as breast cancer and glioblastoma, as well as neurodegenerative diseases.

Fentomycin is a dual-functional lipolysis-targeting chimera (LIPTAC). It specifically targets plasma membrane phospholipids and, following endocytosis, activates lysosomal iron, which promotes phospholipid oxidation and degradation leading to ferroptosis. This compound effectively kills primary sarcoma and pancreatic ductal adenocarcinoma cells, particularly those subpopulations that are metastatic, drug-resistant, and exhibit high CD44 expression. Fentomycin shows antitumor activity.

Dynamin I inhibitor

Cho-Arg is a steroid-based cationic lipid that contains a cholesterol skeleton coupled to an L-arginine head group. It forms a complex with plasmid DNA and decreases plasmid DNA migration in an agarose-gel retardant assay at charge ratios greater than or equal to 4. Cho-Arg facilitates transfection of plasmid DNA into H1299 and HeLa cells in the presence or absence of fetal bovine serum, an effect that is reversed by the lipid raft-mediated endocytosis inhibitor methyl-β-cyclodextrin and the caveolae-mediated endocytosis inhibitor genistein . It is cytotoxic to H1299 cells (IC50 = 88.5 μg/ml).

Dios-Arg is a steroid-based cationic lipid that contains a diosgenin skeleton coupled to an L-arginine head group. It forms a complex with plasmid DNA and decreases plasmid DNA migration in an agarose-gel retardant assay at charge ratio greater than or equal to 4. Dios-Arg facilitates transfection of plasmid DNA into H1299 and HeLa cells in the presence and absence of fetal bovine serum, an effect that is reversed by the lipid raft-mediated endocytosis inhibitor methyl-β-cyclodextrin and the caveolae-mediated endocytosis inhibitor genistein . It has been used, coupled to 1,2-dioleoyl-sn-glycero-3-PE , to bind siRNA and plasmid DNA to form cationic lipid nanoparticles for intracellular transport. Dios-Arg is cytotoxic to H1299 and HeLa cells (IC50s = 83.5 and 74.1 μg/ml, respectively).

2H-Cho-Arg is a steroid-based cationic lipid that contains a 2H-cholesterol skeleton coupled to an L-arginine head group and can be used to facilitate gene transfection. It forms a complex with plasmid DNA (pDNA) and decreases pDNA migration in an electrophoretic mobility shift assay at +/- charge ratios of 4 or higher. 2H-Cho-Arg facilitates transfection of a luciferase gene into H1299 cells, an effect that is reversed by the lipid raft-mediated endocytosis inhibitor methyl-β-cyclodextrin and the caveolae-mediated endocytosis inhibitor genistein , but not by inhibitors of clathrin- or micropinocytosis-mediated endocytosis. It induces cytotoxicity in H1299 cells (IC50 = 92.7 μg/ml).

BLX3887 is an inhibitor of 15-lipoxygenase type 1 (15-LO-1; IC50 = 32 nM in a cell-free enzyme assay).1 It is selective for 15-LO-1 over 15-LO-2, which it does not inhibit, 5-LO (IC50 = 472 nM), and 12-LO (IC50 = 3,310 nM). BLX3887 inhibits the production of 15-LO metabolites selectively in eosinophils over neutrophils when used at a concentration of 10 μM. It also inhibits endocytosis in, and the migration of, isolated human peripheral blood mononuclear cell-derived dendritic cells in vitro. |1. Archambault, A.-S., Turcotte, C., Martin, C., et al. Comparison of eight 15-lipoxygenase (LO) inhibitors on the biosynthesis of 15-LO metabolites by human neutrophils and eosinophils. PLoS One 13(8), e0202424 (2018).

RTIL 13 is a highly effective inhibitor of dynamin GTPase, exhibiting an IC50 value of 2.3 μM for dynamin I GTPase. Furthermore, it selectively interacts with the pleckstrin homology lipid binding domain. This compound effectively suppresses both receptor-mediated and synaptic vesicle endocytosis, demonstrating IC50 values of 9.3 μM and 7.1 μM, respectively.

Biotin-TAT (47-57) is a biotin-tagged transactivator of transcription, commonly employed as a protein transduction domain (PTD) in various primary cells. Its transduction capacity is contingent on ATP and temperature, suggesting the participation of endocytosis.

PD-1/PD-L1-IN-14 (compound 17) is an inhibitor of PD-1/PD-L1 interaction (IC50=27.8 nM) that promotes PD-L1 dimerization, endocytosis, and degradation.