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.

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.

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.

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.

Dynasore (Dynamin Inhibitor I) is a highly selective, reversible small-molecule dynamin inhibitor with an IC₅₀ of 15 μM. Dynasore also inhibits the mitochondrial dynamin Drp1 without affecting other small GTPases. By inhibiting the GTPase activity of dynamin, Dynasore blocks its function in membrane fission, thereby inhibiting clathrin-mediated endocytosis. Dynasore can be used in research on endocytosis, membrane transport, viral entry, and receptor signaling regulation.

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).

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.

CT-996 is an orally active GLP-1 receptor agonist that exhibits preferential cAMP signaling and reduces endocytosis. Oral administration of CT-996 improves glycemic control and reduces body weight and body fat.

Pitstop 2d is a Clathrin inhibitor with an IC50 of less than 2 μM. It binds to the Clathrin N-terminal β-propeller domain, thereby inhibiting Clathrin's function and dynamics and blocking the entry of VSV. Pitstop 2d specifically inhibits clathrin-mediated endocytosis (Endocytosis) and does not interfere with non-clathrin-dependent endocytic processes.

Pitstop 2c is a Clathrin inhibitor with an IC50 of less than 2 μM. It binds to the Clathrin N-terminal β-propeller domain, impairing Clathrin's function and dynamics, and blocking the entry of vesicular stomatitis virus (VSV). Pitstop 2c inhibits clathrin-mediated endocytosis (Endocytosis) but does not inhibit non-clathrin-dependent endocytosis.

TMU454 is a prototype GalNAc-PROTAC conjugate. It binds to ASGPR on the cell membrane and is internalized through ASGPR-mediated endocytosis. TMU454 selectively degrades BRD4 and exhibits anticancer activity against hepatocellular carcinoma.

JNJ-89862175 is an antibody-drug conjugate (ADC) that targets ENPP3. JNJ-89862175 specifically recognizes ENPP3 on the surface of tumor cells; after endocytosis and formation of endosomes, the released payload inhibits microtubule polymerization to block mitosis, ultimately inducing tumor cell apoptosis. JNJ-89862175 is intended for use in studies of ENPP3-positive advanced solid tumors.

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).