Arrestin Activator

Tyr-c [D-Lys-p-F-Phe-Phe-Asp]-D-Pro-NH2 is a multi-opioid receptor (Opioid Receptor) modulator, acting as a MOR/KOR agonist and a DOR antagonist. Tyr-c [D-Lys-p-F-Phe-Phe-Asp]-D-Pro-NH2 activates the G protein-mediated cAMP inhibitory pathway and β-arrestin2 recruitment pathway downstream of MOR, with an EC₅₀ of 159 nM for β-arrestin2 recruitment, an EC₅₀ of 1.1 nM for MOR-mediated calcium mobilization, and an EC₅₀ of 397 nM for KOR. Tyr-c [D-Lys-p-F-Phe-Phe-Asp]-D-Pro-NH2 exhibits potent analgesic activity in vivo. It can be used in studies related to opioid receptor function and analgesia.

Abaloparatide (BA 058) is a parathyroid hormone receptor 1 (PTHR1) analog. Abaloparatide also is a selective PTHR1 activator. Abaloparatide enhances Gs/cAMP signaling and β-arrestin recruitment. Abaloparatide enhances bone formation and cortical structure in mice. Abaloparatide has the potential for the research of osteoporosis.

Abaloparatide TFA (BA 058 TFA) is a parathyroid hormone receptor 1 (PTHR1) analogue. Abaloparatide TFA also is a selective PTHR1 activator. Abaloparatide TFA enhances Gs/cAMP signaling and β-arrestin recruitment. Abaloparatide TFA enhances bone formation and cortical structure in mice. Abaloparatide TFA has the potential for the research of osteoporosis.

SBI-810 hydrochloride is a blood-brain barrier-permeable NTSR1 modulator. SBI-810 hydrochloride promotes the recruitment of β-arrestin-2 to NTSR1 and antagonizes NTSR1-mediated Gq activation. SBI-810 hydrochloride inhibits excitatory synaptic transmission, NMDA receptor and extracellular signal-regulated kinase (ERK) signaling in spinal nociceptive neurons, reduces surface expression of Nav1.7 and action potential firing in primary sensory neurons, and attenuates C-fiber responses. SBI-810 hydrochloride effectively alleviates acute and chronic pain in various rodent models through peripheral and central modulation. SBI-810 hydrochloride is applicable to research related to multiple pain disorders.

Elabela(19-32) is an active fragment of ELABELA (ELA) that binds to apelin receptor (APJ). Elabela(19-32) activates the G_αi1 and β-arrestin-2 signaling pathways with EC₅₀s of 8.6 nM and 166 nM. Elabela(19-32) induces receptor internalization and reduces arterial pressure, exerts positive inotropic effects on the heart.

IHCH-7113 is a 5-HT2AR agonist with EC₅₀ values of 58.9 nM (Gq bioluminescence resonance energy transfer assay) and 44.7 nM (β-arrestin 2 bioluminescence resonance energy transfer assay). IHCH-7113 activates both Gαq-mediated signaling pathways and β-arrestin 2 recruitment pathways. IHCH-7113 is applicable for research related to depression.

Elabela(19-32) TFA is an active fragment of ELABELA (ELA) that binds to apelin receptor (APJ). Elabela(19-32) TFA activates the G_αi1 and β-arrestin-2 signaling pathways with EC₅₀s of 8.6 nM and 166 nM. Elabela(19-32) TFA induces receptor internalization and reduces arterial pressure, exerts positive inotropic effects on the heart.

PW0729 is a selective GPR52 agonist. PW0729 activates G protein/cAMP signaling pathway, with bias toward this pathway over β-arrestin recruitment, and induces GPR52 desensitization. PW0729 can be used for the research of neuropsychiatric and neurological diseases.

SBI-810 is a blood-brain barrier-permeable NTSR1 modulator. SBI-810 promotes the recruitment of β-arrestin-2 to NTSR1 and antagonizes NTSR1-mediated Gq activation. SBI-810 inhibits excitatory synaptic transmission, NMDA receptor and extracellular signal-regulated kinase (ERK) signaling in spinal nociceptive neurons, reduces surface expression of Nav1.7 and action potential firing in primary sensory neurons, and attenuates C-fiber responses. SBI-810 effectively alleviates acute and chronic pain in various rodent models through peripheral and central modulation. SBI-810 is applicable to research related to multiple pain disorders.

ELA-21 (human) is an apelin receptor agonist with a pK_i of 8.52. ELA-21 (human) completely inhibits Forskolin-induced cAMP production and stimulates β-arrestin recruitment with subnanomolar potencies. ELA-21 (human) is an agonist in G-protein-dependent and -independent pathways.

NCGC00135472 is a potent agonist of resolvin D1 receptor (DRV1), with the EC₅₀ of 0.37 nM and 0.05 μM for β-arrestin and cAMP activities, respectively.

MRS542 is a nucleoside A3 AR antagonist with a pK_i of 8.74. MRS542 also acts as a partial agonist (pEC₅₀ = 7.76) in promoting β-arrestin translocation. MRS542 can be converted into an agonist by LUF6000 (HY-13236). MRS542 can be used for cardiovascular disease research.

ISAM-CG557 is a selective CB2R agonist, with a K_i of 54.6 nM. ISAM-CG557 reduces intracellular ROS levels and caspase activity. ISAM-CG557 exhibits significant MAPK bias and moderate G-protein bias, with CB2R EC₅₀s of 0.60 nM (cAMP), 60.9 nM (β-arrestin) and 0.03 nM (MAPK). ISAM-CG557 exerts potent anti-inflammatory effects by reducing pro-inflammatory cytokines and increasing anti-inflammatory cytokines in cells. ISAM-CG557 can be used for the study of neuroinflammatory and neurodegenerative disorders.

AT1R-agonist-1 is an angiotensin II type 1 receptor (AT1R) agonist with a K_i value of 1.4 nM. AT1R-agonist-1 exhibits low Gαq activity, retains β-arrestin recruitment function, and accesses the deep allosteric pocket inside AT1R via its flexible side chain. AT1R-agonist-1 possesses positive inotropic effects (enhancing cardiac contractile function) and causes almost no increase in blood pressure. AT1R-agonist-1 can be used for research on conditions such as refractory cardiogenic shock.

3-Ethoxy-5,6-dibromosalicylaldehyde is an IRE1/ERN1 inhibitor, with an IC₅₀ of 0.12 μM, a K_i of 71-88 nM, and a K_d of 100 nM against the ribonuclease activity of hIRE1α, as well as an IC₅₀ of 4.8 μM against yeast Ire1. It shows selectivity toward IRE1 ribonuclease. 3-Ethoxy-5,6-dibromosalicylaldehyde blocks the IRE1/ERN1-mediated unfolded protein response (UPR) signaling pathway, including XBP-1 mRNA splicing, induction of XBP1 target genes, and activation of MAPK8/9/10, but does not alter the phosphorylation level of IRE1α or the PERK/ATF6 pathway. 3-Ethoxy-5,6-dibromosalicylaldehyde inhibits chikungunya virus replication, induces growth arrest, apoptosis and clonogenic inhibition in pancreatic cancer cells, reduces FB1 (Fumonisin B1) (HY-N6719)-induced autophagy and cell death, regulates PGG-induced senescence and apoptosis, and alleviates Sorafenib (HY-10201)-induced vacuolization and damage in hepatic stellate cells. 3-Ethoxy-5,6-dibromosalicylaldehyde can be used in research related to chikungunya virus infection, pancreatic cancer, FB1-induced nephrotoxicity, liver cancer, breast cancer, lung cancer and liver fibrosis.

ML138 is a blood-brain barrier-permeable κ-opioid receptor (KOR) agonist, with an EC₅₀ value of 0.87 μM and a human K_i value of 2.4 nM for human receptors; it exhibits high selectivity for KOR over μ, δ and other receptors. ML138 activates β-arrestin (beta-arrestin)-mediated signaling pathways, stimulates G protein coupling, and activates the downstream extracellular regulated protein kinase 1/2 (ERK1/2) mitogen-activated protein kinase (MAP kinase) signaling pathway. ML138 is applicable to research related to addictive behaviors.

BMS-986331 is an orally active selective N-Formyl Peptide Receptor 2 (FPR2) agonist with an EC₅₀ of 0.5 nM in humans and 1 nM in rats. BMS-986331 activates Gαi2, GαoA, Gα12, Gα13 signaling pathways, recruits β-arrestin1 and β-arrestin2, and inhibits downstream cAMP. BMS-986331 induces the expression and release of the pro-resolution cytokine IL-10. BMS-986331 improves cardiac structure and function in a rat model of heart failure induced by permanent coronary artery occlusion. BMS-986331 can be used for the research of heart failure.

GPR35 agonist 6 is a potent and selective agonist targeting GPR35, with an EC₅₀ of 12.1 nM against human GPR35. GPR35 agonist 6 activates the human splice variant GPR35b with comparable efficacy, showing an EC₅₀ of 22.1 nM. GPR35 agonist 6 also exhibits weak GPR55 antagonistic activity, with an IC₅₀ of 21.7 μM, and its agonistic activity towards GPR35 is significantly stronger than its antagonistic activity towards GPR55. GPR35 agonist 6 initiates GPR35 downstream signaling by inducing β-arrestin recruitment. GPR35 agonist 6 is used to investigate GPR35-mediated diseases, such as gastrointestinal lesions and gastric cancer.