GPCR/G-Protein

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

<p>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.</p>

<p>Zaladenant is an adenosine receptor antagonist with antitumor properties.</p>

<p>Rodatristat ethyl is an oral TPH1 inhibitor reducing 5-HT levels &amp; lowering PAH at low doses.</p>

<p>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.</p>

<p>Ro 24-4736 is an effective and selective platelet-activating factor antagonist.</p>

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

<p>Abarelix acetate: synthetic GnRHR antagonist, spikes histamine, lowers LH and testosterone temporarily, used in advanced prostate cancer.</p>

<p>Nocloprost (SH 475) is a prostaglandin E2 (PGE2) analog, an EP1 and EP3 receptor agonist with local gastric protection and ulcer healing effects.</p>

<p>Dopamine D3 receptor antagonist-2 is a dopamine D3 receptor selective (Ki=2.16 nM) or multi-targeting dual ligand that shows potential effects in CNS disorders.</p>

<p>Etoperidone is an antidepressant that acts as an orally active reuptake inhibitor for serotonin (serotonin) and noradrenaline (nor-adrenaline). It demonstrates specific binding affinities (Kd) for several receptors: 36 nM at the 5-HT2 receptor, 38 nM at the α1-adrenergic receptor (α1-adrenergic receptor), 85 nM at the 5-HT1A receptor, and 570 nM at the α2-adrenergic receptor (α2-adrenergic receptor).</p>

<p>NMDAR antagonist 5 (Compound A17) is a multi-target antagonist that acts on NMDAR and monoamine transporters (SERT, DAT, and NET). It demonstrates strong NMDAR antagonistic efficacy (IC50= 0.3 μM) and effective activity on monoamine transporters (SERT IC50= 1.1 μM, DAT IC50= 0.7 μM, NET IC50= 2.7 μM). NMDAR antagonist 5 exhibits high safety with low toxicity (hepatic and renal toxicity IC50&gt; 100 μM; cardiac toxicity IC50= 24.5 μM). It has antidepressant properties and is useful for depression research.</p>

<p>1'-Naphthoyl-2-methylindole (Compound 88) acts as a cannabinoid mimic and an inhibitor of Win 55212-2, displaying a 34% inhibition of [3H]Win 55212-2 binding to cannabinoid receptors at a concentration of 3 μM.</p>

<p>MDA77 is a CB2 agonist with an EC50 value of 5.82 nM and exhibits no activity towards CB1.</p>

<p>UR-AK49 (compound 11) is an agonist for the human histamine H1 and H2 receptors. It exhibits an EC50 of 23 nM in the GTPase assay involving hH2R-Gsalpha fusion protein expressed in Sf9 insect cells. UR-AK49 is applicable in neurologically related research.</p>

<p>D3/5-HT receptor modulator-1 (compound 5i) is a selective antagonist of the dopamine D3 and 5-HT2A receptors, and a partial agonist at the 5-HT1A receptor. It exhibits Ki values of 4.5 nM, 11.9 nM, and 15.3 nM for the dopamine D3, 5-HT2A, and 5-HT1A receptors respectively. The compound shows lower affinity for the dopamine D2 receptor, 5-HT2C receptor, and hERG channel. D3/5-HT receptor modulator-1 possesses atypical antipsychotic properties.</p>

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

<p>Selective, high affinity competitive antagonist of the P2Y1 receptor</p>

<p>ASN-1377642 is an NK1 receptor antagonist with a Ki value of 251 nM. It demonstrates antitumor activity in breast cancer cells with high expression of NK1R-Tr.</p>

<p>ATL444 is an adenosine receptor antagonist with affinity (Ki values) for rA1AR, rA2AAR, rA2BAR, and rA3AR of 7.0, 2.5, 61.8, and &gt;1000 nM, respectively.</p>

<p>R-137696 is an orally active 5-HT1A receptor agonist that facilitates the relaxation of the proximal stomach. It is utilized in research related to functional dyspepsia.</p>

<p>Flucopride (Compound 4a) acts as an acetylcholinesterase inhibitor (AChE) with an IC50 value of 24 nM and serves as a partial agonist for the human 5-HT4 receptor (5-HT4R) with a Ki of 9.6 nM for (h)5-HT4R. It promotes non-amyloidogenic processing of APP in COS-7 cells transiently expressing (h)5-HT4R with an EC50 of 23.0 nM. Flucopride is also likely to exhibit significant gastrointestinal tract (GIT) penetration and blood-brain barrier (BBB) permeability, as determined in PAMPA experiments.</p>

<p>AGH-107 is a highly selective 5-HT7 receptor agonist that can cross the blood-brain barrier, featuring a Ki value of 6 nM and an EC50 value of 19 nM. Demonstrating high selectivity for central nervous system targets, AGH-107 also exhibits high metabolic stability and low toxicity in HEK-293 and HepG2 cell cultures.</p>

<p>CRHR1 antagonist 1 (compound 10a) is a non-peptide antagonist of corticotropin-releasing hormone receptor 1 (CRHR1). It serves as a useful tool in the study of psychiatric disorders.</p>

<p>(±)-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.</p>

<p>5-HT6R/MAO-B modulator 1 blocks 5-HT6R and permanently inhibits MAO-B, protects glial cells, and reverses memory loss.</p>

<p>APJ receptor agonist 3 is a highly effective and orally administerable agonist of the APJ receptor, demonstrating a potent EC50 value of 0.027 nM.</p>

<p>TAK-661 is an inhibitor of eosinophil chemotaxis (eosinophil chemotaxis) that significantly alleviates late-phase bronchoconstriction while inhibiting the proliferation of eosinophils in bronchoalveolar lavage (BAL) and their infiltration into the airway walls.</p>

<p>CCR1 antagonist13 is a selective small molecule antagonist of CCR1.</p>

<p>LY 245769 is an inhibitor of leukotriene E4 (LTE4).</p>

<p>(Rac)-Nebivolol, a racemic β1-adrenergic blocker (IC50=0.8 nM), has vasodilatory properties and mitigates ethanol-induced cardiac harm.</p>

<p>UK 432097 is an adenosine A2A agonist.</p>

<p>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.</p>

<p>CB1 antagonist 4 is an inverse agonist of cannabinoid receptor 1 (CB1) with an IC50 of 0.4 nM. It can reduce body weight, improve plasma inflammatory markers, and enhance glucose homeostasis [1].</p>

<p>Teoprolol is a blocker of β-adrenergic receptor.</p>

<p>AM9405: peripheral CB1/5-HT3 agonist, suppresses gut motility, relieves GI disorder symptoms in mice.</p>

<p>PAR-2-IN-2 (compound P-596) is an inhibitor of protease-activated receptor 2 (PAR-2), with an IC50 of 10.79 μM for SLIGKV and an IC50 greater than 200 μM for trypsin.</p>

<p>MrgprX2 antagonist-7 is an anti-allergic agent with significant anti-allergic effects and inhibits mast cell degranulation.</p>

<p>Compound 29 is a potent, CB2-selective antagonist/reverse agonist. Derivatives 23 &amp; 24 offer antinociception; 24 activates cannabinoid/TRPV1 receptors.</p>

<p>CI-624 reduces the secretion and output of hydrogen ions, sodium ions, potassium ions, and pepsin. This compound may be utilized in research focusing on cancer and autoimmune diseases.</p>

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

<p>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.</p>

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

<p>Y1 receptor antagonist 1 is an antagonist of neuropeptide Y1 receptor.</p>

<p>Monlunabant ((S)-MRI-1891), a solid dispersion compound, functions as an inhibitor of the cannabinoid CB1 receptor [1].</p>

<p>LPA2 antagonist 5 (EX1) functions as an antagonist of LPA2, with an IC50 value of 4.05 nM.</p>

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).

<p>Burapitant (SSR 240600) is a novel non-peptide tachykinin neurokinin 1 (NK) receptor antagonist with anti-coke oven and antidepressant activity.</p>

<p>SGL5213 is a potent oral SGLT1 inhibitor (IC50: 29 nM) with potential for treating type 2 diabetes.</p>

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

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

<p>LB-102 is an orally active inhibitor of dopamine D2, D3, and serotonin 5-HT7 receptors, utilized in the study of schizophrenia and other psychiatric disorders.</p>

PF-00446687 is a selective agonist of melanocortin-4 receptor (MC4R) (EC50 of 12 ± 1 nM).

<p>VA012 (compound 11) acts as a positive allosteric modulator (PAM) of the serotonin 5-HT2C receptor. It has been shown to reduce food intake and prevent weight gain during subchronic administration without causing central nervous system-related discomfort. VA012 is applicable in obesity research.</p>

<p>Taranabant: potent CB1 receptor inverse agonist; inhibits agonists with 0.13 nM Ki in vitro.</p>

<p>RS 12254 is a dopamine agonist and antihypertensive agent.</p>

<p>Cicaprost (ZK 96480) is an IP agonist with artery relaxing effects; EC50 is 5.8 nM.</p>

<p>Henagliflozin (SHR3824): an oral, selective SGLT2 inhibitor, weak on SGLT1.</p>

<p>Revexepride, a 5-HT4 agonist, may boost CYP3A4, used for treating GERD.</p>

<p>5-HT2A and 2C receptor antagonist</p>

<p>Selective oral S1P1 agonist 5 inhibits lymphocyte drainage, potential for MS research.</p>

<p>Bometolol Hydrochloride is a beta-adrenergic blocking compound used for the treatment of cardiovascular disease.</p>

<p>Beloxepin is an oral dual selective inhibitor of serotonin and norepinephrine uptake.</p>

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

<p>AH22921 is an EP4 prostaglandin receptor antagonist with the ability to antagonize the activation of adenylyl cyclase by prostaglandins in CHO cells. It induces a rightward shift in the PGE? concentration-response curve in these cells, functioning as a non-competitive antagonist. AH22921 is selective for the EP4 receptor, inhibiting its activity in CHO cells without affecting the PGE? concentration-response curve in NPE cells that contain the EP2 receptor.</p>

<p>TAK-637 is a tachykinin 1 (NK1) receptor antagonist.</p>

BMS-986120: Oral, reversible PAR4 antagonist. IC50: 9.5 nM (human), 2.1 nM (monkey). Potent, selective antiplatelet.

<p>MK-8825 is a CGRP receptor antagonist.</p>

<p>Setomagpran is an antagonist of the mas-related G protein-coupled receptor (MRGPR) and possesses anti-inflammatory properties.</p>

<p>Aclidinium, a dual-action compound, serves as a long-acting muscarinic antagonist and a β2-adrenoceptor (β2-AR) agonist, exhibiting bronchodilator properties. It effectively reduces lung hyperinflation, enhances lung function, and prolongs exercise endurance time. This compound is commonly utilized in studies focusing on chronic obstructive pulmonary disease (COPD).</p>

<p>Aplaviroc, a potent CCR5 inhibitor, binds selectively, blocking HIV entry and specific monoclonal antibody attachment in vitro.</p>

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

Monohydroxy Netupitant is a highly selective antagonist of NK1 receptor, and is Netupitant metabolite.

<p>CVT-5440 is a selective, high-affinity (2B) adenosine receptor antagonist with good selectivity.</p>

<p>SphK1-IN-1: SphK1 ATPase inhibitor, IC50=2.48 μM, potential for cancer research.</p>

<p>IMP-1575 is a highly effective inhibitor of hedgehog acyltransferase (HHAT), with an IC50 of 0.75 μM when inhibiting purified HHAT. IMP-1575 has potential applications in cancer research.</p>

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

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

<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.</p>

<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>

Tofogliflozin specifically inhibits SGLT2; IC50s are 2.9 nM (human), 14.9 nM (rat), 6.4 nM (mouse).

<p>MK-3207 Hydrochloride (MK-3207 HCl) is a potent CGRP receptor antagonist with IC50 and Kiof 0.12 nM and 0.022 nM, highly selective versus human AM1, AM2, CTR, and AMY3. Phase 2.</p>

<p>(1R,2S,3R)-Aprepitant (Compound ent-4) is a competitive antagonist of the human neurokinin-1 (NK-1) receptor. It holds potential for research in the treatment of nausea and vomiting related to cancer or postoperative conditions.</p>

<p>GAT564, an allosteric CB1R modulator, shows EC50s of 87 nM (cAMP) &amp; 320 nM (β-arrestin2) and lowers IOP effectively in glaucoma mice.</p>

<p>Compound 10 is a potent dual A1/A3 AR antagonist, with Ki values of 37.6 nM (hA1), 25.4 nM (hA3), and 1.47 nM (rA1), studied in renal, lung, and Alzheimer's.</p>

<p>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.</p>

<p>Rivenprost, selective EP4 agonist (Ki: 0.7 nM), promotes bone growth, osteoblast differentiation, and aids wound healing.</p>

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

<p>RF9 hydrochloride is a potent and selective Neuropeptide FF receptor antagonist that acts on hNPFF1R (Ki: 58 nM) and hNPFF2R (Ki: 7 nM).</p>

<p>MRS2179 blocks turkey P2Y1 receptor (Kb 102 nM, pA2 6.99), affects platelet aggregation, and has varying IC50s on P2 receptors.</p>

<p>Disulergine is a dopamine receptor agonist. It also prolactin release-inhibiting 8 alpha-amino-ergoline.</p>

<p>U75302 is an antagonist of thymosin beta-4 (TB4) receptor with a Ki value of 159 nM on guinea pig lung membranes.</p>

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

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

<p>INCB-9471 HCl: a potent CCR5 antagonist, blocks monocyte migration &amp; HIV-1.</p>

<p>SJPYT-310 is a selective PXR antagonist, exhibiting no noticeable cytotoxicity.</p>

<p>SB 224289: selective 5-HT1B antagonist, pKi 8.2, 60x selectivity, effective orally.</p>

<p>Tipelukast (KCA 757), an oral drug for asthma research, blocks leukotrienes and fights inflammation and fibrosis.</p>

<p>LPA2 antagonist 3 (compound 15) serves as an Lp(a) antagonist. Lp(a) is a pathogenic risk factor for atherosclerotic cardiovascular disease (ASCVD).</p>

<p>Compound 21a: Oral GnRH-R antagonist, IC50=0.57 nM, potent against prostate cancer/prevents LH surges.</p>

<p>Pareptide monohydrochloride is a metabolically stable analog of melatonin inhibitor (MIF).</p>

<p>LPA2 antagonist 6 (example 2) acts as an antagonist of Lp(a). It inhibits the formation of Lp(a) with an IC50 value of 2.33 nM, making it useful for cardiovascular disease research.</p>