β subtype

Luzindole (N-0774) is a selective melatonin receptor antagonist that inhibits experimental autoimmune encephalomyelitis and exhibits antidepressant-like activity. It preferentially targets MT2 (Mel1b) over MT1 (Mel1a), with Ki values of 10.2 nM for human MT2 and 158 nM for MT1.

EP4 receptor antagonist 7 (Compound 14) is an antagonist of the prostaglandin E2 (PGE2) receptor subtype EP4, with an IC50 of 1.1 nM. This compound inhibits PGE2-induced β-arrestin recruitment in HEK293 cells with an IC50 of 0.9 nM. In RAW 264.7 macrophages, it reduces the expression of PGE2-induced IL-4, macrophage mannose receptor 1 (Mrc1), chitinase-like protein 3 (Chil3), chemokine (C-X-C motif) ligand 1 (Cxcl1), triggering receptor expressed on myeloid cells 2 (Trem2), and arginase 1 (Arg1) mRNA. In the CT26 mouse colon cancer model, EP4 receptor antagonist 7, combined with an anti-PD-1 antibody, inhibits tumor growth and enhances CD8+ T cell infiltration into the tumor.

Donecopride is a partial agonist of the serotonin (5-HT) receptor subtype 5-HT4E(Ki= 8.5 nM) and an inhibitor of acetylcholinesterase (AChE; IC50= 16 nM).1It is selective for AChE over butyrylcholinesterase (BChE; IC50= 3,530 nM) but does bind to 5-HT2Band sigma-2 (σ2) receptors (Ki= 1.6 nM for both) in a panel of 42 neurotransmitter receptors and transporters. Donecopride induces release of soluble amyloid precursor protein-α (sAPP-α) in COS-7 cells transiently expressing 5-HT4with an EC50value of 11.3 nM. Oral administration of donecopride (1 mg/kg) reduces brain soluble and insoluble amyloid-β (1-42) levels and increases the time spent exploring the novel object in the novel object recognition (NOR) test in the 5XFAD transgenic mouse model of Alzheimer's disease. Donecopride (3 mg/kg, p.o.) prevents a reduction in spontaneous alternation behavior induced by intracerebroventricular administration of soluble Aβ42 (sAβ42) in the Y-maze in mice.2 1.Lecoutey, C., Hedou, D., Freret, T., et al.Design of donecopride, a dual serotonin subtype 4 receptor agonist/acetylcholinesterase inhibitor with potential interest for Alzheimer's disease treatmentProc. Natl. Acad. Sci. USA111(36)E3825-E3830(2014) 2.Rochais, C., Lecoutey, C., Hamidouche, K., et al.Donecopride, a Swiss army knife with potential against Alzheimer's diseaseBr. J. Pharmacol.177(9)1988-2005(2020)

Afloqualone (HQ-495) is a quinazolinone family GABAergic drug that acts as an agonist of the β subtype of the GABAa receptor, exhibiting sedative and muscle-relaxant effects.

PI3Kγ inhibitor 4 is a selective, potent, orally active PI3Kγ inhibitor (IC50: 40 nM). PI3Kγ inhibitor 4 is ~7-fold more selective for PI3Kγ than the α subtype, 43-fold more selective than the β subtype and 18-fold more selective than the δ subtype. inflammation.

Bopindolol ((±)-Bopindolol) fumarate is an orally active β-adrenoceptor (ARs) antagonist with partial agonist activity, non-selective for β1- and β2-ARs, and with low affinity for the β3-AR subtype. It is a precursor to Pindolol and is used to study primary and renal vascular hypertension.

Scorpion toxin Tf2, a β-scorpion toxin first identified in the venom of the Brazilian scorpion Tityus fasciolatus, acts as an activator of the neuronal voltage-gated sodium (Nav) subtype Nav1.3, associated with epilepsy and nociception. It increases hNav1.3 activation voltage, prompting channel opening at resting membrane potentials [1].

EP4 antagonist 14 is a prostaglandin E2 receptor subtype EP4 antagonist, demonstrating an IC50 of 1.1 nM in a HEK293 human receptor reporter assay and blocking β-arrestin recruitment due to PGE2 with an IC50 of 0.9 nM. At 10 µM, it reduces PGE2-stimulated mRNA levels of Il-4, macrophage mannose receptor 1 (Mrc1), chitinase-like protein 3 (Chil3), chemokine (C-X-C) motif ligand 1 (Cxcl1), triggering receptor expressed on myeloid cells 2 (Trem2), and arginase-1 (Arg1) in RAW 264.7 macrophages. When used at 30 mg/kg per day alongside anti-PD-1 antibodies, it curbs tumor growth and enhances CD8+ T cell infiltration in tumors using a CT26 murine colon cancer model.

ZTA-261 is a highly selective and low-toxicity agonist for the thyroid hormone receptor subtype β (THR-β), with an IC50 of 6.3 nM. It operates through the Liothyronine-mediated pathway to reduce body weight and visceral fat. This compound has applications in the study of lipid metabolism and obesity.

Bopindolol is an orally active antagonist of β-adrenoceptors (ARs) with partial agonist activity. Bopindolol is non-selective for β1- and β2-ARs and has low affinity for β3-AR subtype. Bopindolol is a prodrug of pindolol and can be rapidly metabolized to an active hydrolyzed form. Bopindolol can be used for essential and renovascular hypertension research [1] [2].