β subtype

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.

BIBO3304 TFA is an effective, orally active, and selective neuropeptide Y (NPY) Y1 receptor antagonist (IC50:0.38 and 0.72 nM for the human and the rat Y1 receptor).

GFB-8438 is a potent and subtype selective inhibitor of TRPC5(IC50s of 0.18 and 0.29 μM of hTRPC5 and hTRPC4, respectively).

Flindokalner (BMS-204352) is a potassium channel modulator and a positive modulator of all neuronal Kv7 channel subtypes expressed in HEK293 cells. It is also a positive modulator of large conductance calcium-activated K channels (BKca) and displays negative modulatory activity at Kv7.1 channels (Ki = 3.7 μM). Additionally, Flindokalner acts as a negative modulator of GABAA receptors and demonstrates anxiolytic efficacy in vivo.

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.

CDPPB is a modulator of mGluR5 positive allosteric(with an EC50 of 27 nM in Chinese hamster ovary cells expressing human mGluR5).

Difamilast is an inhibitor of phosphodiesterase IV.

AGN 205327 is a potent synthetic agonist of retinoic acid receptors (RARs), with EC50 values of 3766 nM for RARα, 734 nM for RARβ, and 32 nM for RARγ, and AGN 205327 demonstrates no inhibitory activity against retinoid X receptors (RXRs), thereby exhibiting selective receptor subtype targeting that makes AGN 205327 an important tool for probing retinoid signaling pathways and investigating therapeutic applications of RAR activation.

β-Naltrexamine dihydrochloride is an orally administered, irreversible opioid receptor antagonist. Its derivatives exhibit optimised subtype selectivity and can be used for pain research.

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)

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].