agonism

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

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.

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.

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.

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 a potent PPARγ binding agent (IC50: 24 nM) with antidiabetic effects, inhibiting CDK5-mediated PPARγ Ser273 phosphorylation (IC50: 160 nM) and displaying minimal PPARγ agonism.

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.

Thrombospondin-1 (1016-1023) [human, bovine, mouse], a segment of Thrombospondin-1 (TSP-1), functions as a CD47 agonist.

Compound 114 (D3R/MOR antagonist 1) exhibits dual antagonistic activity at dopamine D3 receptors (D3R) and mu-opioid receptors (MOR), with K i values of 46.5 nM and 691 nM, respectively. It offers analgesic benefits through partial agonism at MOR and may decrease the risk of opioid misuse through its D3R antagonistic properties [1].

Compound 121, a D3R/MOR antagonist with K i values of 361 nM and 85.2 nM for D3R and MOR respectively, has the potential for analgesic effects through MOR partial agonism and may reduce opioid-misuse liability through D3R antagonism [1].

Compound 46, designated as MOR agonist-2, serves as a D3R antagonist and a MOR agonist with respective K i values of 7.26 nM and 564 nM. This compound holds potential for analgesic effects attributed to its partial agonism at MOR and may decrease opioid misuse liability owing to its antagonistic action at D3R [1].

Ac-DArg-c[Cys-Glu-His-DPhe-Arg-Trp-Cys]-NH2 is a synthetic cyclic octapeptide acting as a melanocortin-4 receptor (MC4R) agonist, significantly elevating heart rate and blood pressure [1].

MOR agonist-3 (Compound 84) is a dual D3R/MOR antagonist with Ki values of 382 nM and 55.2 nM, respectively. It shows promise for analgesia via partial agonism at MORs and may mitigate opioid abuse via D3R antagonism. This compound is utilized in research pertaining to inflammation and neuropathic pain [1].