non-classical

Fezolamine is a novel orally available non-tricyclic compound with antidepressant activity. It is three to two times more selective in blocking synaptosomal uptake of [3H]norepinephrine than uptake of [4H]3-hydroxytryptamine or [3H]dopamine in vitro. It blocked the inhibitory effects of rifampicin and tetraphenyl in classical behavioral tests using monoamine-depleted animals.

2,2,2-Trichloroethanol, the active form of the sedative hypnotic drug chloral hydrate, is an agonist for the nonclassical K2P channels TREK-1 (KCNK2) and TRAAK (KCNK4). It activates a nonclassical potassium channel in cerebrovascular smooth muscle and dilates the middle cerebral artery [1]. [1]. Nikhil K Parelkar, et al. 2,2,2-trichloroethanol Activates a Nonclassical Potassium Channel in Cerebrovascular Smooth Muscle and Dilates the Middle Cerebral Artery. J Pharmacol Exp Ther. 2010 Mar;332(3):803-10.

Foxy-5 Ammonium Salt is a WNT5A agonist, a mimetic peptide of WNT5A, a non-classical member of the Wnt family.Foxy-5 Ammonium Salt triggers cytoplasmic free calcium signaling without affecting β-catenin activation and inhibits migration and invasion of epithelial cancer cells.Foxy-5 Foxy-5 Ammonium Salt effectively reduces the metastatic spread of prostate cancer cells with low WNT5A expression in an in situ mouse model.

AM7499 is a non-selective cannabinoid receptor agonist with remarkably high in vitro and in vivo potency. It is readily hydrolysed by plasma esterases and to be less prone to deposition in bodily fat than existing classical cannabinoid agonists.

Antibacterial agent 197 (compound 1-deAA) functions as a termination inhibitor targeting non-classical anhydroglycosyl receptors and anhydrowall peptide-type peptidoglycan (PG) within bacterial TGase and exhibits efficacy against Staphylococcus aureus. It acts synergistically with Vancomycin, serving as its antibacterial adjuvant [1].

Zimberelimab, a fully human IgG4 monoclonal antibody targeting PD-1 with high affinity and selectivity, exhibits antitumor activities. It is applicable in research on various cancers, including cervical cancer, non-small cell lung cancer, and classical Hodgkin’s lymphoma [1].

Sintilimab (IBI308) is a humanized IgG4 monoclonal antibody with significant anti-tumor activity that restores endogenous anti-tumor T-cell responses by binding to PD-1 and thereby blocking the interaction of PD-1 with its ligands (PD-L1 and PL-L2).Sintilimab is used in combination with other compounds for the treatment of classical Hodgkin's lymphoma, non-cellular lung cancer and esophageal cancer. Sintilimab is used in combination with other compounds to treat classical Hodgkin's lymphoma, non-small cell lung cancer and esophageal cancer.

Arachidoyl ethanolamide, a saturated fatty acyl ethanolamide lacking classical (CB1/CB2) activity, plays a role in a complex system comprising central cannabinoid (CB1), peripheral cannabinoid (CB2), and non-CB receptor-mediated pharmacology. This system has paved the way for extensive research in diverse fields such as memory, weight loss and appetite, neurodegeneration, tumor surveillance, analgesia, and inflammation. Unlike other compounds, Arachidoyl ethanolamide does not bind to the murine CB1 receptor nor does it compete with anandamide for the fatty acid amide hydrolase, the endocannabinoid hydrolytic enzyme. The non-CB receptor-mediated actions of saturated ethanolamides like Arachidoyl ethanolamide are currently under investigation.

L-Homopropargylglycine is an alkyl chain-based PROTAC linker utilized in the synthesis of PROTACs[1].

Polzastobart (JTX-8064), a humanized IgG4 monoclonal antibody, functions as an antagonist selectively targeting LILRB2. It inhibits its interaction with both classical and non-classical MHC I molecules. By preventing LILRB2 from binding to HLA-A/B and HLA-G, which are associated with immunotolerance in cancer cells, Polzastobart promotes the production of pro-inflammatory cytokines in macrophages, thereby serving as a macrophage immune checkpoint inhibitor [1].