GPCR/G-Protein

(±)-Penbutolol ((Rac)-Penbutolol) is the racemic form of Penbutolol. It acts as an orally active β-adrenergic receptor antagonist. (±)-Penbutolol mitigates the tachycardia induced by exercise, reduces the increase in peak expiratory flow rate (PEFR) caused by physical activity, and decreases plasma renin activity (PRA) at rest. The peak plasma concentration of this compound is achieved one hour after oral administration, with a half-life of 4.5 hours, and it is metabolized into active metabolites in the body. This compound is utilized in research related to cardiovascular diseases.

CCR4 antagonist 2 (Compound 31) is a novel potent, orally bioavailable small molecule antagonists of CC chemokine receptor 4 (CCR4) that inhibits Treg

AFP 07 free acid is a 7,7-difluoroprostacyclin derivative. It also acts as a selective and highly potent agonist for the IP receptor.

RBM10-8 irreversibly inhibits human sphingosine-1- phosphate lyase (hS1PL) while behaving also as an enzyme substrate.

Atumelnant (CRN04894) is an MC2R antagonist used in the study of congenital adrenocortical hyperplasia (CAH) and Cushing's disease (CD).

Rocavorexant is an antagonist of the orexin-1 receptor (orexin-1 receptor), exhibiting a pIC50 value of 9.1 for human OX1 and a pIC50 of 6.0 for human OX2.

Compound (−)-19, also known as (-)-5-HT2C agonist-3, is a selective 5-HT2C agonist exhibiting a preference for Gq signaling. It demonstrates efficiency with EC50 values for 5-HT2 receptor subtypes as follows: 5-HT2C at 103 nM, 5-HT2B at 570 nM, and 5-HT2A at 72 nM. This compound is utilized in research on antipsychotics.

PD 135158 is a CCK2 receptor antagonist.

Oral antiplatelet agent 1 is a potent antiplatelet agent with an IC50 of 2.94 μM in vitro.

Compound 2o, also known as CB2R/5-HT1AR agonist 1, serves as a partial orally active agonist for the CB2 receptor (EC50 = 479.6 nM) and a full agonist for the 5-HT1A receptor (EC50 = 2.7 μM). This compound demonstrates both anti-anxiety and anti-depressive effects and has favorable pharmacokinetic properties [1].

Lisuride: an oral D2 dopamine agonist, ergot derivative, used in Parkinson's, migraine, and high prolactin research.

Potent, oral SSTR5 antagonist 2 TFA may treat type 2 diabetes.

Dopamine D 3 receptor ligand is a potent, selective, high-affinity dopamine D3 receptor ligand that is 89 times more selective for D3 (Ki: 8 nM) than D2 (Ki:

A3AR antagonist 5 (Compound 16) acts as a selective antagonist for the human adenosine A3 receptor (human adenosine A3 receptor), with an affinity expressed as a pC value of 4.542 μM.

Acyline, a GnRH antagonist, suppresses gonadotropins and testosterone in animals and maintains the effect for 2 weeks in men with one dose.

K-14585 blocks PAR(2), reduces NFkappaB activity, and IL-8 response, but alone can boost IL-8.

SJPYT-310 is a selective PXR antagonist, exhibiting no noticeable cytotoxicity.

AAZ-A 154 hydrobromide is a selective, competitive, non-hallucinogenic 5-HT2AR antagonist. It promotes neuronal growth in rodents and yields enduring beneficial behavioral effects.

AAZ-A 154 hydrochloride is a selective, competitive, non-hallucinogenic antagonist of 5-HT2AR. It promotes neuronal growth in rodents and results in enduring beneficial behavioral effects.

5-HT1A modulator 4 (Compound 1) is a ligand for the 5-HT receptor, with Ki values of 2.18 μM for 5-HT1A and 19.7 μM for 5-HT2A.

9-Methyl-β-carboline is a cognitive enhancer with neuroprotective, neurorestorative, and anti-inflammatory properties. Its behavioral effects may be linked to hippocampal dopamine levels and the stimulation of dendritic and synaptic proliferation.

MRGPRX2 modulator-1 (example 17), a modulator of the mas-related G-protein receptor X2 (MRGPRX2), is employed in studies focused on inflammation, pain, and autoimmune disorders [1].

PGD2 is involved in allergy, asthma, sleep, temperature regulation, inhibits clotting, and relaxes blood vessels; PGDM, its metabolite, is a biomarker.

LTD4 antagonist 1 is a potent and orally active antagonist of leukotriene D4 (LTD4; Ki: 0.57 nM).

BAY 38-7271: potent neuroprotective, selective CB1/CB2 agonist, Ki of 1.85 nM (CB1) & 5.96 nM (CB2).

<p>Metrazoline (o-Methyl-tracizoline) acts as a ligand for adrenergic receptors (low affinity) and imidazoline I2 receptors.</p>

Alixorexton is an agonist of the orexin-2 receptor (orexin-2 receptor) and is utilized in obesity research.

NPR-C activator 1 is an activator of the natriuretic peptide receptor C (NPR-C), which can be used to study cardiovascular diseases.

Orvepitant is a potent and selective NK1 antagonist, which may be potentially useful for patients with major depressive disorder (MDD), anxiety and insomnia.

AM8936: potent CB1 agonist, EC50 rCB1=8.6nM/hCB1=1.4nM, Ki rat CB1=0.55nM; potential for CNS, metabolic, pain, glaucoma research.

Compound 18g, a potent A1AR blocker with Ki: 2.08 nM (hA1), 6.91 nM (hA2A), 31.2 nM (hA2B).

5-HT1A antagonist; Ki=8nM, Kb=0.04nM. PDE4B IC50=80.4μM; PDE7A IC50=151.3μM. Good biofilm penetration, stable, anticognitive, antidepressant.

Osanetant HCl is the (R)-enantiomer; neurokinin-3 receptor antagonist

SS-RJW100 is an enantiomer of RJW100 targeting LRH-1, SF-1, enhances Tif2 interaction, and disrupts LRH-1 networks with lowered stability.

CP-608039 is a selective adenosine A3 receptor agonist for both human A3 and human A1 receptors.

SSTR5 antagonist 6, an orally active antagonist specific to the somatostatin receptor subtype 5 (SSTR5), exhibits an IC50 value of 24 nM. This compound is utilized in researching type 2 diabetes [1].

ONO-9780307 is a specific antagonist of LPA1 (lysophosphatidic acid receptor 1) (IC50: 2.7 nM).

U92016A hydrochloride: potent, orally active 5-HT1A agonist, metabolically stable, high intrinsic activity, Ki=0.2 nM.

GRPR antagonist-1 targets GRPR, kills specific cancer cells (e.g., PC3, Pan02, HGC-27), and promotes apoptosis by modulating Bcl-2 and Bax.

OP-2507, a prostacyclin agonist, is used potentially for the treatment of hepatic insufficiency and hypertension.

Apafant (WEB 2086) is a PAF antagonist that blocks eosinophil activation and can be used to study experimental allergic conjunctivitis in guinea pigs.

Tonapofylline, orally active, selectively blocks A1 adenosine receptor (Ki: 7.4 nM), used in heart failure research.

Thielavin B, from Thielavia terricola, inhibits prostaglandin E2 synthesis and reduces rat oedema.

Neladenoson is an effective and selective agonist of the Adenosine A1 Receptor (A1R). EGFR-IN-162 shows potential for research in heart failure.

Opipramol (Ensidon) is an atypical tricyclic antidepressant (TCA) primarily functioning as a sigma (σ) receptor agonist. It interacts effectively with sigma recognition sites, having a Ki value of 50 nM. Opipramol is applicable in the study of generalized anxiety disorder (GAD).

SAR-114137 is a histone sphingomyelin kinase inhibitor used in the study of molluscum arteriosum and peripheral neuropathic pain.

CS-0777 is a potent, selective, and orally active S1P1 agonist (sphingosine 1-phosphate receptor modulator).

<p>SR 142948-C3-NHMe is the methylated form of SR 142948.</p>

SB 258741 hydrochloride is a potent antagonist of the 5-HT 7 receptor, designed specifically for studying schizophrenia [1].

Pentacosafluorotridecanoic Acid (PFTrDA) is a perfluoroalkyl substance (PFAS) that exhibits various biological impacts across different species. In zebrafish embryos, exposure to PFTrDA induces yolk sac edema and increases mRNA expression of thyroid hormone synthesis genes, including tshβ, at concentrations of 0.1 and 0.3 mg/L. At a dosage of 10 mg/kg, PFTrDA reduces serum testosterone and luteinizing hormone levels, as well as palmitic acid, linoleic acid, and oleic acid levels in the testicular interstitial cells of late adolescent rats. In humans, maternal plasma levels of PFTrDA during pregnancy are positively correlated with the development of eczema in female infants (but not male infants), and PFTrDA levels are higher in the livers of cancerous humans compared to non-cancerous ones. Additionally, PFTrDA is found in marine mammals.

SGLT1/2-IN-1 is a dual SGLT1/SGLT2 inhibitor.

MRS2279 diammonium, a P2Y1 antagonist with K i 2.5 nM, IC 50 51.6 nM, blocks ADP-induced platelet aggregation, pK b 8.05.

Elsovaptan is an antagonist of the vasopressin receptor and is applicable for research in Alzheimer's disease.

SPL-IN-1 (compound C17) acts as a dual species inhibitor of sphingosine-1-phosphate lyase [1].

AL 6598, a prodrug of PGD2 agonist AL 6556, reduces IOP by 53% at 1μg twice daily in monkeys; binds DP receptors with Ki of 3.2μM.

8-iso PGF3α is an isoprostane produced from the free-radical peroxidation of EPA.

AFP-07 is a highly selective and potent agonist. It was used for the prostacyclin receptor.

Y1 receptor antagonist 1 is an antagonist of neuropeptide Y1 receptor.

LY210073 is an antagonist of the Leukotriene B4 (LTB4) receptor (IC50: 6.2 nM).

Spns2-IN-3 (compound 510) is an SPNS2 inhibitor with an IC50 value of 1.2 μM for hSPNS2. It is applicable in research on autoimmune diseases such as multiple sclerosis (MS) and inflammatory bowel disease (IBD), as well as fibrosis, muscle atrophy, metastasis, acute lung injury, rheumatoid arthritis, colitis, Alzheimer's disease, and other conditions linked to SPNS2 activity.

Tixanox sodium effectively blocks histamine release in the lungs triggered by anti-IgE. It has also been demonstrated that when administered orally, Tixanox sodium can successfully counteract exercise-induced asthma.

YM158 free base is a potent and selective antagonist of TXA2 and LTD4 receptor (pA2s: about 8.81 and 8.87).

Meluadrine, a potent agonist of the β2 adrenergic receptor, is one of the metabolites of Tulobuterol [1].

Iloprost, a potent prostacyclin analog, binds IP & EP1 receptors (Ki 11 nM), contains 16(S/R) isomers, and inhibits platelets (IC50 65 nM).

FDU-PB-22, a novel synthetic cannabinoid, undergoes rapid metabolism in human liver microsomes (HLM) with a half-life of 12.4 minutes.

O-1269 acts as a partial agonist for the cannabinoid receptor 1 (CB1R), with a binding affinity (Ki) of 32 nM. Additionally, it exhibits analgesic properties.

AB-FUBINACA 3-fluorobenzyl isomer is a synthetic cannabinoid and an indazole derivative, exhibiting high affinity for central CB1 receptors (Ki= 0.9 nM) and possessing anticonvulsant activity.

12(S)-HEPE, made from EPA by 12-LO, is an anti-inflammatory ω-3 derivative affecting leukotriene formation.

Dinoxyline is a potent dopamine receptor agonist, with dissociation constants (Ki values) for D1, D2, D3, and D4 receptors being 7 nM, 6 nM, 5 nM, and 43 nM, respectively. It is utilized in neuroscience research.

<p>S1PR1 agonist 1 is a potent agonist of S1PR1. S1PR1 agonist 1 has potential in autoimmune diseases.</p>

M1069 is an oral A2A/A2B receptor antagonist, 100x more selective over A1/A3, with antitumor properties by blocking adenosine's immunosuppressive effects.

Elzasonan hydrochloride is a serotonin 1B and serotonin 1D receptor antagonist. It is utilized in the study of depression.

Selective, orally active PAR-1 antagonist with an IC50 of 7 nM, potential for cardiovascular disease studies.

CCR7-Cmp2105 is a thiadiazole-dioxide allosteric antagonist for CCR7 with a Kd of 3 nM and IC50 of 7.3 μM against arrestin binding.

LPA receptor antagonist-1 (example 52) serves as an antagonist for the lysophosphatidic acid (LPA) receptor and is applicable in various types of studies [1].

Selective, high affinity competitive antagonist of the P2Y1 receptor

SB-423557 is an orally active antagonist of calcium-sensing receptor (CaR) with IC50 of 520 nM

GnRH antagonist 2 is a GnRH receptor antagonist, useful for studying endocrine diseases.

Anti-MRSA agent 19 (Compound 1) is an antibiotic that exhibits activity against Staphylococcus aureus. It is active against 40 clinical isolates from the CDC, representing diverse bacterial species with various resistance factors, including resistance to vancomycin, aminoglycoside/tetracycline, and oxazolidinone (median MIC=4 μg/mL).

CGRP antagonist 7 is a potent calcitonin gene-related peptide receptor (CGRP) antagonist with a Ki value of 0.029 nM. It effectively inhibits CGRP receptor-mediated cyclic adenosine monophosphate (cAMP) production, with an IC50 value of 1.5 nM. This compound is useful in migraine research.

<p>HU-308, a synthetic cannabinoid analogue, is a highly selective agonist of the CB2 receptor. It demonstrates an affinity for the CB2 receptor that is over 440 times greater than its affinity for the CB1 receptor, which are predominantly found in immune cells. This compound plays a crucial role in modulating the immunosuppressive effects of the endocannabinoid system (ECS). Additionally, HU-308 possesses anti-inflammatory and neuroprotective properties, and it regulates the function of microglia. Its potential applications include research into neuroinflammation and retinal diseases.</p>

NBI 35965 hydrochloride is a selective CRF1 (corticotropin-releasing factor receptor 1) antagonist that is both orally active and capable of penetrating the brain. It possesses a K i value of 4 nM and a pK i of 8.5, and does not affect CRF2. This compound effectively diminishes CRF or stress-triggered ACTH (adrenocorticotropic hormone) production in vivo, demonstrating pIC 50 values of 7.1 and 6.9. Additionally, NBI 35965 hydrochloride exhibits anxiolytic properties [1] [2].

Compound 12a (D1R antagonist 1) is a D1R antagonist that participates in both G-protein-coupled and β-arrestin-mediated signaling pathways [1].

BIIE-0246: A potent, non-peptide Y2 receptor antagonist; >650-fold more selective than Y1, Y4, Y5.

AM11638 is an endogenous cannabinoid analogue that targets cannabinoid receptors (CB1 and CB2 receptors), exhibiting analgesic properties. It shows potential for research in neurological disorders and inflammation-related diseases.

SSTR4 agonist5 (Compound 5) is an orally active agonist of the somatostatin receptor 4 (SSTR4) with an EC50 of 0.228 nM. It demonstrates good stability in human/rat liver microsomes and can inhibit mechanical hyperalgesia in rat models.

(Rac)-BI 703704 is a potent activator of soluble guanylyl cyclase (sGC).

WIN 66306: Cyclic heptapeptide, blocks NK1/NK2 receptors, inhibits substance P-triggered contractions in guinea pig ileum.

MRT-92 is an antagonist of Smoothened (Smo) with anti-cancer activity, featuring a binding affinity (Ki) of 0.7 nM. It inhibits the Hedgehog signaling pathway by obstructing the overlapping binding sites within the transmembrane domain of the Smoothened receptor and suppresses the proliferation of cerebellar granule cells in rodents (IC50=0.4 nM). MRT-92 is utilized for research into cerebellar gliomas.

GRK6-IN-5 is an inhibitor of the GRK6 polypeptide, with an IC50 of 4.48 μM. GRK6-IN-5 is utilized in research focused on hematological malignancies, inflammatory diseases, and autoimmune disorders.

Remlifanserin is a potent inverse agonist of the serotonin receptor (5-HT2A).

<p>Mrgx2 antagonist-3 (Compound B-40) is a highly selective antagonist of the MrgX2 receptor, with an IC50 range of 0.042-2.5 nM. It blocks downstream G protein signaling and β-arrestin recruitment, inhibiting Mrgx2 receptor-mediated calcium influx and cell degranulation. Mrgx2 antagonist-3 shows potential for research in inflammation-associated diseases and pruritus, such as chronic urticaria and allergic asthma.</p>

Neflumozide (HRP 913) is an orally effective derivative of benzisoxazole, characterized by its potent dopamine antagonist properties and antipsychotic activity. It is utilized in research related to psychiatric disorders.

Sigma-2 Radioligand 2 (compound 4) exhibits low nanomolar affinity for the σ2 receptor (Ki=2.30 nM) and high subtype selectivity (Ki(σ1)/Ki(σ2) > 1500).

AzoLPA ammonium is a photoswitchable lipid that activates signaling of lysophosphatidic acid receptors 1-5 (LPA1-5).

<p>EP4 receptor agonist 3 is an activator of the EP4 receptor and is useful for research in the DSS-induced colitis mouse model.</p>

PF-07054894: potent CCR6 antagonist, targets GPCR, for inflammatory bowel disease research.

LTB4 dimethyl amide: inhibits human neutrophil degranulation and rat lysozyme release; antagonizes LTB4 receptor on guinea pig lung membranes (Ki = 130 nM).