GPCR/Proteína-G

<p>Zafirlukast metabolite M1 (compound 15) is an inhibitor used in the treatment of asthma and other allergic pulmonary conditions, effectively antagonizing leukotriene activity.</p>

<p>PF-06372222: a small-molecule that modulates GCGR and antagonizes GLP-1R, affecting insulin and glucagon.</p>

<p>Nedocromil sodium is a pharmacologic stabilizer of mast cells, has been shown to normalize cytokine levels and attenuate cardiac remodeling.</p>

<p>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.</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>

LK-11, an alkaloid derivative, inhibits the passive uptake of norepinephrine (NA) by synaptic vesicles in the thalamus, similarly to cocaine.

<p>Potent 5-HT6/5-HT2A receptors dual antagonist with K i of 11 nM &amp; 39 nM.</p>

<p>PD 140376: Selective CCK-B/gastrin receptor antagonist radioligand for guinea pig stomach &amp; brain.</p>

<p>5-HT2A/5-HT2C inverse agonist 1 serves as a dual and potent inverse agonist for the 5-HT2A and 5-HT2C receptors, with hERG inhibition properties that mitigate cardiovascular risks. Demonstrating significant antipsychotic efficacy in the MK-801-induced mouse model, this compound holds potential for psychosis research.</p>

<p>CHF-6366: M3 antagonist &amp; β2 agonist (pKi 10.4/11.4), mild Ca channel blocker, used in COPD study.</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>PGD2 is involved in allergy, asthma, sleep, temperature regulation, inhibits clotting, and relaxes blood vessels; PGDM, its metabolite, is a biomarker.</p>

<p>L-796778 acetate is a selective sst3 receptor agonist. In CHO-K1 cells expressing hsst3 receptors, it acts as a partial agonist that inhibits Forskolin-induced cAMP production, with an IC50 value of 18 nM. Additionally, L-796778 acetate exhibits anticonvulsant properties.</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>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.</p>

<p>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.</p>

<p>5-HT2 receptor antagonist</p>

<p>KF26777 is a potent and selective antagonist of adenosine A3 receptor.</p>

8 Hydroxy PIPAT oxalate is a selective 5-HT1A receptor agonist that enhances the spontaneous release of histamine by promoting the degranulation of mast cells in guinea pig and human intestinal preparations. By activating the serotonin signaling pathway, this compound demonstrates potential in regulating gastrointestinal functions and offers insight into the management and suppression of functional gastrointestinal disorders such as irritable bowel syndrome. Its effects in increasing histamine release could play a crucial role in gastrointestinal regulation.

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

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

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

<p>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:</p>

<p>MRS4865 (compound 7a) serves as a chimeric antagonist for the P2Y14 receptor and an agonist for UDP-glucose, offering protection against neuropathic pain.</p>

<p>F 14679 is a potent 5-HT1A agonist (pKi=10.23) with a maximum Ca2t response similar to 5-HT.</p>

<p>SGLT inhibitor-1 is a potentsodium glucose co-transporter proteins (SGLTs) dual inhibitor(hSGLT1 and hSGLT2 with IC50s of 43 nM and 9 nM, respectively).</p>

<p>SB 243213 dihydrochloride is an orally active, selective and high-affinity antagonist of 5-hydroxytryptamine (5-HT)2C receptor(pKi of 9.37 and a pKb of 9.8 for</p>

<p>L-657926 is a stereoselective antagonist of the thromboxane A2 (TxA2) receptor, composed of (-)-9-chlorobenzyl-6-fluoro-1,2,3,4-tetrahydrocarbazol-1-yl acetic acid and (+)-9-chlorobenzyl-6-fluoro-1,2,3,4-tetrahydrocarbazol-1-yl acetic acid. The IC50 values for the (-) and (+) configurations against TxA2 are 0.27 nM and 124 nM, respectively.</p>

<p>GPR27 agonist-1 (compound I) is a selective agonist for GPR27 with a pEC50 value of 6.34.</p>

<p>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.</p>

<p>SB 224289: selective 5-HT1B antagonist, pKi 8.2, 60x selectivity, effective orally.</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>BD-1047 is a selective functional antagonist of sigma receptors. It can alleviate climbing behavior induced by Apomorphine and head twitching caused by Phencyclidine.</p>

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

<p>ASP-2205, a 5-HT2C receptor agonist (human 5-HT2C receptor, EC50=0.85 nM; rat 5-HT2C receptor, EC50=2.5 nM), enhances the urethral closure reflex mediated by the genital nerve, thereby preventing urinary incontinence.</p>

<p>HU 433, a synthetic cannabinoid, acts as a CB2 receptor agonist and is an enantiomer of HU 308. It provides anti-inflammatory and neuroprotective effects by binding to the CB2 receptor, primarily found on immune cells, thereby modulating immune responses and inflammation. Additionally, HU 433 influences microglial signaling pathways, particularly LPS and IFNγ-mediated routes, affecting the phosphorylation of MAPKs, including ERK1/2, JNK, p38, and Akt. This compound is valuable in researching neuroinflammation and retinal diseases.</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>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>

<p>Pexacerfont (BMS-562086) is a selective antagonist of the corticotropin-releasing factor receptor (IC50: 6.1±0.6 nM for the human CRF1 receptor).</p>

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

<p>SORT1-IN-5 (compound 3) is a SORT1 inhibitor capable of crossing the blood-brain barrier. The MSOH salt form of SORT1-IN-5 exhibits a certain degree of oral bioavailability.</p>

<p>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>

<p>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.</p>

<p>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.</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>

SAR-150640, a selective β3-adrenergic receptor agonist, prevents an increase in MMP activity and production observed after LPS stimulation or in cases of chorioamnionitis.

<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>Compound 6.4, also known as 5-HT7R antagonist 3, is a selective antagonist of the 5-HT7R with a Ki of 8 nM. It exhibits significantly less affinity towards D2R, 5-HT1AR, and 5-HT2AR with Ki values of 511 nM, 8930 nM, and 5786 nM, respectively. In mice, 5-HT7R antagonist 3 demonstrates anti-depressant and anti-anxiety activities.</p>

<p>RGS10 modulator-1 (compound 15) is an effective regulator of RGS10. It significantly reverses IFNγ-induced expression of both RGS10 protein and mRNA, as well as COX-2 mRNA and iNOS expression triggered by IFNγ.</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>

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.

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

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

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

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

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

<p>LX2761 is a stable inhibitor for SGLT1/2 with IC50s of 2.2/2.7 nM; it targets SGLT1 in the GI tract.</p>

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

<p>GLP-1 receptor agonist 15 (Example 4) is a GLP receptor agonist with an EC50 of 0.74 nM. It exhibits an IC50 of 10.1 μM against the hERG potassium ion channel. This compound is applicable for research in the diabetes field.</p>

<p>2,3-dinor-11β-Prostaglandin F2α (2,3-dinor-11β-PGF2α) was recovered from the urine of both normal monkeys and humans when infused with radiolabeled PGD2, where</p>

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

LRH-1 modulator-1: potent agonist, boosts IL-10, reduces IL-1b/TNFa, anti-inflammatory in gut.

<p>COX-2-IN-6: Potent, selective COX-2 inhibitor; oral; IC50 0.84μM, Ki 69nM; blocks PGE2 synthesis; prevents colorectal cancer.</p>

<p>AChE/BChE-IN-21 is an antagonist of the histamine H3 receptor, a calcium channel blocker, and an acetylcholinesterase inhibitor. It exhibits neuroprotective activities against H2O2 and Aβ1-40, and can restore cognitive functions in AD mice.</p>

<p>P2Y2 and P2Y4 receptor agonist</p>

<p>Mafoprazine, a phenylpiperazine derivative, exhibits varying affinities for neuronal receptors, primarily exerting its antipsychotic effects through blocking D2 receptors and enhancing α-adrenergic activity. It also increases the activity of dopamine metabolites.</p>

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

<p>Aplaviroc (AK 602), a SDP derivative, is a CCR5 antagonist. With IC50s of 0.1-0.4 nM for HIV-1Ba-L, HIV-1JRFL and HIV-1MOKW.</p>

<p>PF-4693627 is an effective and selective microsomal prostaglandin E synthase-1 inhibitor (IC50=3 nM).</p>

<p>Potent D4R antagonist-2: selective, IC50=6.52 μM, good in vitro PK and brain penetration, potential for Parkinson's research.</p>

<p>ZK118182 isopropyl ester is a PG analog with potent DP-agonist activity (EC50 = 16.5 nM) and high affinity for the DP receptor (Ki = 74 nM).</p>

<p>AL-8810 is an 11β-fluoro analog of PGF 2α with selective antagonist effects at the PGF 2α receptor (FP receptor) [1].</p>

<p>Nifeviroc (TD-0232) is an orally active CCR5 antagonist, useful in HIV-1 infection research.</p>

<p>Arpromidine (BU-E-50) acts as an agonist for the histamine H2 receptor and an antagonist for the histamine H1 receptor. It demonstrates positive inotropic effects with a lower risk of inducing arrhythmias. Arpromidine can be utilized in studies related to congestive heart failure.</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>YM158 free base is a potent and selective antagonist of TXA2 and LTD4 receptor (pA2s: about 8.81 and 8.87).</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>

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

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

<p>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].</p>

<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].</p>

<p>AChE-IN-5: oral, crosses blood-brain barrier, targets AChE/5-HT1A/SERT, potent with 2.29 nM IC50.</p>

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

<p>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.</p>

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

<p>APJ receptor agonist 8 is a small molecule agonist of the APJ receptor, enhancing load-independent cardiac contractility in isolated perfused rat hearts.</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>CP-608039 is a selective adenosine A3 receptor agonist for both human A3 and human A1 receptors.</p>

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

<p>Bzo-poxizid is a synthetic cannabinoid and a psychoactive substance.</p>

<p>CB1/2 receptor-1 (compound 5.3) serves as an agonist for CB1/2 receptors and is utilized in angiogenesis research.</p>

<p>Substituted piperidines-1 can promote the release of growth hormone in humans and animals.</p>

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

<p>GLP-1 receptoragonist 16 (Example 53) is a GLP-1 agonist applicable for research in diabetes, obesity, or diseases related to non-alcoholic steatohepatitis.</p>

<p>Serlopitant is a selective antagonist of Neurokinin-1 (NK-1) receptor.</p>

<p>Befiradol HCl (NLX-112) is a selective 5-HT1A receptor agonist with anxiolytic effects and prevents ATXN3 aggregation.</p>

<p>Oral CCR1 antagonist A1B1 targets h/m/rCCR1 (IC50: 0.03/0.58/0.32 μM), potential for treating inflammatory diseases.</p>

<p>inhibitor of human CCR5 binding to HIV-1 gp120</p>

<p>Toladryl is a derivative of Diphenhydramine that can cross the blood-brain barrier and exhibits oral activity, with antihistamine and anticholinergic properties. Its anticholinergic effects are approximately a tenth of those seen with Diphenhydramine, yet it offers 2-4 times the protection against lethal doses of histamine in guinea pigs. The side effects of Toladryl are fewer and milder compared to Diphenhydramine; however, at higher doses, it may cause symptoms such as insomnia, agitation, and disorientation related to the central nervous system. Toladryl is utilized in the research of allergic diseases.</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>Tiprenolol hydrochloride is a β-adrenoceptor (β-adrenoceptor) antagonist. This compound is effective in eliminating ventricular arrhythmias in dogs caused by intravenous administration of adrenaline, following inhalation of halothane.</p>

<p>SGLT1/2-IN-8 (compound 8) is a potent and orally active dual inhibitor of SGLT1/2, exhibiting IC50 values of 4 nM and 1 nM, respectively. It shows antihyperglycemic properties, making it suitable for related research.</p>