nachr agonist cmpi hydrochloride

CMPI hydrochloride, a potent and selective nAChR agonist, functions as a positive allosteric modulator (PAM) specifically targeting the α4:α4 subunit interface of the nAChR. It enhances the response of the (α4)3(β2)2 nAChR to acetylcholine (ACh) (10 μM) with an EC 50 of 0.26 μM. With its potential for researching nicotine dependence and various neuropsychiatric conditions linked to reduced brain cholinergic activity, CMPI hydrochloride stands as a significant compound in neurological research.

TLR7 8 agonist 4 hydroxy-PEG6-acid hydrochloride, a Drug-Linker Conjugate for ADC synthesis, is the hydrochloride variant of TLR7 8 agonist 4 hydroxy-PEG6-acid, with the TLR7 8 agonist 4 component attached to the hydroxy-PEG6-acid linker [1].

α7 nAchR-JAK2-STAT3 agonist 1 is a potent inhibitor of the α7 nAchR-JAK2-STAT3 pathway that acts on nitric oxide (NO) (IC50: 0.32 μM). It has demonstrated positive effects on iNOS, IL-1β, and IL-1β in murine macrophages RAW264.7, and inhibited the expression of iNOS, IL-1β, and IL-6 in mouse macrophages. Additionally, α7 nAchR-JAK2-STAT3 agonist 1 suppressed LPS-induced NO release, NF-κB activation, and cytokine production, making it useful for studying sepsis.

Compound 8, identified as a selective alpha4beta2 (α4β2) neuronal acetylcholine receptor (nAChR) agonist, demonstrates a dissociation constant (Kd) of 26 nM, indicating high affinity for this receptor subtype.

TLR7 8 agonist 4 hydroxy-PEG10-acid hydrochloride (compound 9) is a drug-linker conjugate used in antibody-drug conjugates (ADCs) with high tumor efficacy. It consists of TLR7 8 agonist 4, a potent TLR7 8 agonist, linked to the ADC linker hydroxy-PEG10-acid, which can be cleaved.

nAChR agonist 1 (DUN71755) is a brain-permeable and orally efficacious positive allosteric α7 nicotinic acetylcholine receptor (α7 nAChR)modulator.

Compound 8b hydrochloride, a selective S1R agonist, exhibits affinity with K i s of 1.1 nM for S1R and 88 nM for S2R. It demonstrates neuroprotective effects against ROS and NMDA-induced neurotoxicity [1].

TLR8 agonist 2 hydrochloride is a highly potent and selective agonist for human TLR8, with an EC50 of 3 nM, but demonstrates significantly weaker activity towards human TLR7 (EC50 of 33.33 μM).

Potent positive allosteric modulator of α4β2 nAChRs (EC50 values are 20 and 18 nM for rat and human, respectively). Selective for hα4β2 over hα3β2, hα3β4 and hα7. Inhibits (α4)2(β2)3, muscle-type and Torpedo nAChRs (IC50 values are 0.5, 0.7 and 0.2 μM, respectively), but not (α4)3(β2)2 receptors. Exhibits ability to photoincorporate into aliphatic and nucleophilic amino acid side chains. Hamouda (2016) Photolabeling a nicotinic acetylcholine receptor (nAChR) with an (α4)3(β2)2 nAChR-selective positive allosteric modulator. Mol.Pharmacol. 89 575 PMID:26976945 |Albrecht et al (2008) Discovery and optimization of substituted piperidines as potent, selective, CNS-penetrant α4β2 nicotinic acetylcholine receptor potentiators. Bioorg.Med.Chem.Lett. 18 5209 PMID:18789861 |Wang et al (2017) Unraveling amino acid residues critical for allosteric potentiation of (α4)3(β2)2-type nicotinic acetylcholine receptor responses. J.Biol.Chem. 292 9988 PMID:28446611

S1R Agonist 1 (Compound 6b) hydrochloride is a selective S1R agonist, displaying K i values of 0.93 nM for S1R and 72 nM for S2R, and has demonstrated neuroprotective effects against ROS and NMDA-induced neurotoxicity [1].