agonism

SB 258719 is a selective antagonist of 5-HT7 receptor(pKi of 7.5).

KN-62 is a potent and specific Ca2+/calmodulin-dependent protein kinase II (CaMKII) inhibitor with Ki of 0.9 μM.

AZD9496 maleate is a highly potent and selective antagonist of the estrogen receptor alpha (ERα), exhibiting an IC50 value of 0.28 nM. This compound, AZD9496 maleate, is an orally bioavailable selective estrogen receptor degrader (SERD).

Tirzepatide (LY3298176) Acetate (2023788-19-2 free base) is a new molecule that can control blood glucose levels by combining dual agonism of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors.[3]

OP-3633 is an effective and selective steroidal glucocorticoid receptor (GR) antagonist (IC50: 29 nM). OP-3633 shows low progesterone receptor (PR) agonism and androgen receptor (AR) antagonism. It also has an inhibition of GR transcriptional activity.

GSK-7227, a novel compound representing a novel class of peroxisome proliferator-activated receptor delta (PPARδ) partial agonists, demonstrates potent partial agonistic activity by upregulating the expression of PPARδ target genes, specifically carnitine palmitoyltransferase 1a (CPT1a) and pyruvate dehydrogenase kinase 4 (PDK4), in cultured skeletal muscle cells, indicating its potential role in modulating skeletal muscle metabolism and energy homeostasis.

Org GC 94 is a psychoactive small-molecule compound belonging to the tetracyclic antidepressant (TeCA) therapeutic family, extensively characterized as a noradrenergic and specific serotonergic antidepressant (NaSSA) with clinically documented antidepressant, anxiolytic, hypnotic, antiemetic, orexigenic, and antihistamine pharmacological effects. Org GC 94 mechanistically acting as an antagonist or inverse agonist at H1, 5-HT1D, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT3, 5-HT6, 5-HT7, α1-adrenergic, and α2-adrenergic receptors, inhibiting norepinephrine reuptake, exhibiting high-affinity H1 inverse agonism associated with sedation and weight gain, showing negligible affinity for muscarinic acetylcholine receptors and thus lacking anticholinergic effects.

COR659 is a GABAB positive allosteric modulator (PAM) . COR659 suppresses alcohol and chocolate self-administration in rats[1]. COR659 apparently exerts its effects via a composite mechanism, including positive allosteric modulation of the GABAB receptor and an action at the cannabinoid CB1 receptor[3]. COR659 (0, 2.5, 5 and 10 mg/kg) treatment is completely ineffective on lever-responding (FR10) for regular food pellets in food-deprived Wistar rats[1].COR659 is able to suppress lever-responding for a sucrose solution in sP rats and a chocolate solution in Wistar rats[2]. Animal Model: Male sP and Wistar rats[1]. [1]. Paola Maccioni, et al. Suppressing effect of COR659 on alcohol, sucrose, and chocolate self-administration in rats: involvement of the GABA B and cannabinoid CB 1 receptors. Psychopharmacology (Berl). 2017 Sep;234(17):2525-2543. [2]. Francesca Ferlenghi, et al. The GABA B receptor positive allosteric modulator COR659: In vitro metabolism, in vivo pharmacokinetics in rats, synthesis and pharmacological characterization of metabolically protected derivatives. Eur J Pharm Sci. 2020 Dec 1;155:105544. [3]. Paola Maccioni, et al. Anti-addictive properties of COR659 - Additional pharmacological evidence and comparison with a series of novel analogues. Alcohol. 2019 Mar;75:55-66.

NXN-188 is a novel dual-action small molecule compound that combines inhibition of neuronal nitric oxide synthase (nNOS) with 5-HT receptor agonism and is currently in development for the treatment of acute migraine.

SC-17599 exhibits dose-dependent analgesic effects in both the acetic acid-induced writhing test and the hot-water tail withdrawal test. This compound also induces a Straub tail reaction in a dose-dependent and naltrexone-sensitive manner, akin to morphine. However, unlike morphine, high doses of SC-17599 do not affect motor activity. Overall, SC-17599 demonstrates selective μ-opioid receptor agonism, showing behavior effects similar to morphine, with some differences.

5-Iodowillardiine is a selective agonist for specific kainate receptor subunits that robustly activates GluK1 (GluR5) and GluK5 (KA2)-containing receptors while displaying minimal activity at AMPA receptors and no measurable agonism toward GluK2 (GluR6) subunits. Despite its excitotoxic neurotoxic activity in vivo, 5-Iodowillardiine remains a powerful experimental tool for dissecting kainate receptor subtype distribution, synaptic function, and excitatory neurotransmission in the brain and spinal cord.

Aganodine is a guanidine that activates presynaptic imidazoline receptors. Aganodine inhibits the presynaptic release of norepinephrine through its agonism at imidazoline receptors.

BIO592 is a modulator of RORγt. BIO592 triggers inverse agonism of RORγ.

Navafenterol saccharinate (AZD-887 saccharinate) is an inhaled, dual-acting, potent, selective, and long-lasting M3-antagonist/β2-agonist that demonstrates high affinity for the human M3 receptor with a pIC50 of 9.5 and strong β2-adrenoceptor agonism with a pEC50 of 9.5. Navafenterol provides a sustained bronchoprotective and antisialagogue effects with a favorable cardiovascular safety profile, and serving as a valuable investigational compound for chronic obstructive pulmonary disease research.

Fabomotizole hydrochloride (CM346 hydrochloride), an anxiolytic drug, produces anxiolytic and neuroprotective effects. The mechanism of Afobazole remains poorly defined, however, with GABAergic, NGF, and BDNF release promoting, MT1 receptor antagonism, MT3 receptor antagonism, and sigma agonism suggested as potential mechanisms. Afobazole inhibits MAO-A reversibly and there might be also some involvement with serotonin receptors.

PPARγ phosphorylation inhibitor 1 (Compound 10) is an effective PPARγ agonist (IC50=24 nM) that inhibits CDK5-mediated PPARγ Ser273 phosphorylation (IC50=160 nM) and exhibits antidiabetic activity.

SC13, a novel mitragynine analog, exhibits low-efficacy agonism at Mu opioid receptors and provides antinociception while minimizing adverse effects.

PPARγ agonist 1 is a potent agonist of PPARγ that efficiently activates hPPARγ without causing full agonism, thereby avoiding adverse effects. pparγ agonist 1 has shown research potential in cardiovascular diseases associated with metabolic disorders.

OL-135 is a CNS-penetrant, highly potent, and selective reversible inhibitor of FAAH, exhibiting analgesic pharmacology in various animal models without causing the motor impairment associated with direct CB1 agonism.

Fabomotizole, also known as Afobazole, Obenoxazine and CM346, is an anxiolytic drug launched in Russia in the early 2000s. It produces anxiolytic and neuroprotective effects without any sedative or muscle relaxant actions. Its mechanism of action remains poorly defined however, with GABAergic, NGF- and BDNF-release-promoting, MT1 receptor agonism, MT3 receptor antagonism, and sigma agonism suggested as potential mechanisms. Fabomotizole was shown to inhibit MAO-A reversibly and there might be also some involvement with serotonin receptors.

Fadolmidine, also known as MPV-2426, is a novel and potent alpha2 -adrenoceptor (alpha2) -AR) agonist developed for spinal analgesia. Fadolmidine displayed high affinity and full agonist efficacy at all three human alpha2-adrenoceptor subtypes (A, B and C) in transfected CHO cells with EC50 values (nM) of 0.4, 4.9 and 0.5, respectively. Fadolmidine inhibited also electrically evoked contractions in rat vas deferens demonstrating the activation of rodent presynaptic alpha2D-adrenoceptors with an EC50 value of 6.4 nM. Moreover, fadolmidine was a full agonist at human alpha1A-adrenoreceptor (EC50 value 22 nM) and alpha1B-adrenoreceptor (EC50 value 3.4 nM) in human LNCaP cells and transfected HEK cells, respectively. Agonism at the alpha1-adrenoceptor was also observed in rat vas deferens preparations although at lower potency (EC50 value 5.6 microM). Fadolmidine demonstrated potent alpha2-adrenoceptor agonist activity also in vivo by inhibiting electrically induced tachycardia i......

PF-04479745, also known as PF-4479745, is a potent and selective 5-HT2C agonist (EC50 = 10 nM). PF-4479745 displayed robust pharmacology in a preclinical canine model of stress urinary incontinence (SUI) and no measurable functional agonism at the key selectivity targets 5-HT2A and 5-HT2B in relevant tissue-based assay systems.

Romergoline, a newly synthesized ergoline-derivative, shows a unique pharmacological profile, displaying a full dopamine (DA) antagonism in normal animals but a full DA agonism in"denervated" animal models.

FX-909 is a covalent peroxisome proliferator–activated receptor gamma (PPARγ) inverse agonist developed for advanced solid malignancies, including muscle-invasive bladder cancer, and functional profiling and NMR studies demonstrate that FX-909 exhibits enhanced corepressor-selective inverse agonism and superior stabilization of a transcriptionally repressive PPARγ ligand-binding domain conformation compared with T0070907.