internalization

SEW 2871 is an orally available, highly selective S1P1 agonist with an EC50 of 13.8 nM.It reduces the number of lymphocytes in the blood and is used in studies related to diabetes, Alzheimer's disease, liver fibrosis, and inflammation. It activates ERK, Akt and Rac signaling pathways and induces S1P1 internalization and recycling.

NUCC-390, a novel small-molecule CXCR4 receptor agonist, selectively induces CXCR4 receptor internalization while acting antagonistically to AMD3100. This compound facilitates nerve functional recovery following neurodegeneration in vivo.

Kukoamine B mesylate is a novel cationic alkaloid derived from dermatophytes with antioxidant activity, inhibits LPS internalization in Kupffer and RAW 264.7 cells, and can be used to study acute inflammation and diabetes.

CYM5442 is an S1P agonist, targeting to Sphingosine.

Rasarfin inhibits Ras and ARF6.

ELA-14(human) acetate is a fragment of ELA that binds to APJ, activates the Gαi1 and β-arrestin-2 signaling pathways, and induces receptor internalization similarly to its parent endogenous peptide.

ACT-389949 is a potent and selective agonist of formyl peptide receptor type 2 (FPR2) Lipoxin A4 receptor (ALX), with an EC50 of 3 nM for FPR2 ALX internalization into monocytes. It has the potential for the treatment of inflammatory disorders.

Tephrosin induces degradation of of EGFR and ErbB2 by inducing internalization of the receptors, has potent antitumor activities.

R 59-022 (DKGI-I) is a diacylglycerol kinase (DGK) inhibitor and a 5-HT Receptor antagonist that blocks filovirus internalization in host cells. R 59-022 activates protein kinase C (PKC), inhibits intestinal smooth muscle contractility, and enhances O2- production induced by 1-oleoyl-2-acetylglycerol.

BQ0413 exhibits high affinity for PSMA, with a dissociation constant (KD) of 89 pM. It demonstrates effective uptake and internalization, with an internalization rate of 44% in PC3-pip cells. After being labeled with [99mTc], BQ0413 can serve as an imaging agent for tumors.

Selective medium-chain free fatty acid receptor GPR84 agonist (EC50 = 139 nM). Exhibits no response at GPR40, GPR41, GPR119 or GPR120 at 100 μM. Activates calcium mobilization, inhibits cAMP accumulation, and induces ERK1/2 phosphorylation, receptor desensitization and internalization in vitro. Liu et al (2016) Design and synthesis of 2-alkylpyrimidine-4,6-diol and 6-alkylpyridine-2,4-diol as potent GPR84 agonists. ACS Med.Chem.Lett. 7 579 PMID:27326330 |Zhang et al (2016) Discovery and characterization of a novel small-molecule agonist for medium-chain free fatty acid receptor G protein-coupled receptor 84. J.Pharmacol.Exp.Ther. 357 337 PMID:26962172

RWJ-56110 dihydrochloride is a potent, selective, peptide-mimetic inhibitor of PAR-1 activation and internalization (binding IC50=0.44 μM), showing no effect on PAR-2, PAR-3, or PAR-4. It inhibits the aggregation of human platelets induced by SFLLRN-NH2 (IC50=0.16 μM) and thrombin (IC50=0.34 μM), with high selectivity relative to U46619. RWJ-56110 dihydrochloride also blocks angiogenesis and the formation of new vessels in vivo, and induces cell apoptosis[1][2].

R-8507 is a small molecule antagonist of the TNF-α type 1 receptor (TNF-αRI). It inhibits the expression of intercellular adhesion molecule-1 (ICAM-1) induced by TNF-α and IL-1β with EC50 values of 2.45 and 3.79 μM, respectively, in an ELISA using A549 lung epithelial cells.{|Gururaja2007|} It also disrupts the interaction of the TNF-αRI with receptor interacting protein 1 (RIP1) and TNF-αR-associated death domain protein (TRADD), preventing internalization of the receptor complex.

S1p receptor agonist 1 (S1p-receptor-agonist-1) is an S1P receptor agonist.

NUCC-390 dihydrochloride, a novel and selective CXCR4 receptor agonist, effectively induces the internalization of CXCR4 receptors and acts antagonistically to AMD3100 [1]. This small-molecule compound has demonstrated the ability to facilitate functional nerve recovery following neurodegeneration in vivo [2].

HF51116 is a potent antagonist of CXCR4 that significantly inhibits SDF-1α-induced cell migration, calcium mobilization, and CXCR4 internalization. It also prevents HIV-1 infection utilizing CXCR4. HF51116 has shown investigational potential for HIV-1 infection, hematopoietic stem cell mobilization, and cancer metastasis.

Epofolate is folate receptor-targeting antimitotic agent with potential antineoplastic activity. Folate receptor-targeted epothilone BMS753493 contains an epothilone moiety linked to a single folate molecule. Mediated through the folate moiety, this agent delivers the antimitotic epothilone component into cells expressing folic acid receptors, frequently upregulated in many types of tumor cells. After ligand-receptor internalization, the epothilone moiety induces microtubule polymerization and stabilizes microtubules against depolymerization, resulting in the inhibition of mitosis and cellular proliferation. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).

PD-1 PD-L1-IN-29 (S4-1) is a potent inhibitor of the PD-1 PD-L1 interaction with an IC50 value of 6.1 nM. It effectively binds to PD-L1, promoting its dimerization and internalization, enhancing its localization to the endoplasmic reticulum, and demonstrating anticancer activity.

Bufrolin, an analog of Cromoglycate (histamine release inhibitor) and a potent agonist of GPR35, enhances the interaction between β-arrestin-2 and both human GPR35a and rat GPR35. It stabilizes mast cells, exhibiting antiallergic properties, and inhibits anti-inflammatory responses triggered by internalization peptides. Furthermore, Bufrolin is researched for its anti-inflammatory properties in pharmaceutic applications associated with internalization peptides [1] [2] [3].

Anticancer agent 81 (Compound 37b3) induces tumor cell cycle arrest and apoptosis, and serves as a payload for conjugation with Trastuzumab, forming the antibody-drug conjugate (ADC) T-PBA, which retains Trastuzumab's targeting and internalization properties [1].

MC-GGFG-AM-(10Me-11F-Camptothecin) serves as a linker-payload conjugate in the synthesis of ZW251, an antibody-drug conjugate (ADC) targeting human GPC3. ZW251 comprises a humanized IgG1 antibody linked to ZD06519, a novel camptothecin-based topoisomerase 1 inhibitor, through a maleimide-anchor and a cleavable glycyl glycyl phenylalanyl glycine (GGFG)-aminomethyl (AM) linker. ZW251 demonstrates strong affinity for GPC3 in both human and cynomolgus monkey cells, characterized by rapid internalization in GPC3-positive Hepatocellular Carcinoma (HCC) cell lines and induces bystander-mediated killing of GPC3-negative cancer cells [1].

Elabela(19-32) TFA, an effective fragment of ELABELA (ELA), selectively engages with the apelin receptor (APJ). This compound initiates G αi1 and β-arrestin-2 signaling, demonstrating EC50 values of 8.6 nM and 166 nM, respectively. It facilitates receptor internalization, lowers arterial pressure, and has a positive inotropic impact on cardiac function [1].

CCZ01048 TFA, an α-MSH analogue, demonstrates a strong binding affinity for the melanocortin 1 receptor (MC1R), displaying a K i value of 0.31 nM. It exhibits rapid internalization into B16F10 melanoma cells and maintains high in vivo stability. CCZ01048 TFA holds potential as an effective agent for PET imaging of malignant melanoma [1].

Targefrin is a potent antagonist targeting EphA2, exhibiting a dissociation constant of 21 nM and an IC50 value of 10.8 nM for the EphA2-LBD. It promotes receptor internalization and degradation across multiple pancreatic cancer cell lines [1].