GPCR/Proteína-G

<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>

<p>ATX inhibitor 27 (Compound 31) is an ATX inhibitor. It demonstrates IC50 values of 13 nM against human autotaxin (hATX) and 23 nM against lysophosphatidylcholine (LPC). By inhibiting the ATX enzyme, ATX inhibitor 27 reduces LPA levels in the body. This compound is applicable in research related to ATX-LPA-associated conditions such as inflammation, neurodegenerative disorders, and cancer.</p>

<p>A1 adenosine receptor antagonist</p>

<p>L 668750 is an inhibitor of platelet-activating factor.</p>

<p>BAY-3153 is a selective CCR1 ( C-C motif chemokine receptor 1 ) antagonist (human IC 50 =3 nM ; rat IC 50 =11 nM ; mice IC 50 =81 nM) .</p>

<p>FK-3657 is a non-peptide antagonist of bradykinin (BK)-B2 receptor.</p>

<p>RS 61756-007 is a selective thromboxane receptor (TP) agonist.</p>

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

<p>Taprostene (CG-4203), a stable Prostacyclin analogue, protects endothelium and myocardium post-ischemia in cats, with minimal hemodynamic impact.</p>

<p>Enprostil: synthetic PGE2 analog, reduces gastric acid, protects mucosa, lowers post-meal gastrin, treats ulcers effectively and safely.</p>

<p>KMN-80 is a potent, selective EP4 agonist with IC50 3 nM, spurring osteoblast differentiation, and showing in vivo bone repair efficacy.</p>

<p>TAK-075 is an orally active CaSR antagonist with an IC50 value of 0.94 nM. It transiently stimulates parathyroid hormone (PTH) secretion in rats and effectively prevents significant reduction in PTH secretion due to the accumulation of active metabolites, thereby maintaining a normal secretion pattern. TAK-075 is applicable in research related to metabolic diseases and osteoporosis.</p>

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

<p>BI-44370, a CGRP (calcitonin gene-related peptide) receptor antagonist, can be used to treat migraines and other chronic pain.</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>inhibitor of human CCR5 binding to HIV-1 gp120</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>

<p>SSTR5 antagonist 2 hydrochloride: potent, oral SSTR5 blocker with potential in type 2 diabetes research.</p>

<p>VGD071, a compound that targets sortilin, presents a promising avenue for forthcoming research utilizing mouse models of breast cancer.</p>

Danavorexton is an orexin receptor agonist.

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

<p>AA 497, a beta-2 agonist, causes relaxation and suppresses Ca spike frequency.</p>

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

<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>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>Beloxepin is an oral dual selective inhibitor of serotonin and norepinephrine uptake.</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>MK-8825 is a CGRP receptor antagonist.</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>(Rac)-Nebivolol, a racemic β1-adrenergic blocker (IC50=0.8 nM), has vasodilatory properties and mitigates ethanol-induced cardiac harm.</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>5-HT7R antagonist 1 is a G protein-biased antagonist with Ki of 6.5 nM for 5-HT 7R.</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>

TAK-024 is an inhibitor of platelet(IC50s of 31, 79 and 51 nM in human, monkey and guinea pig, respectively).

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

<p>Rodatristat is an effective tryptophan hydroxylase 1 and TPH2 inhibitor (IC50s: 33 nM and 7 nM, respectively).</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>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>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>F 14679 is a potent 5-HT1A agonist (pKi=10.23) with a maximum Ca2t response similar to 5-HT.</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>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>(R)-BAY-899: R-isomer, selective LH-R antagonist, effective on hLH (IC50: 185 nM) and rLH (IC50: 46 nM), orally active.</p>

<p>Kendomycin is a proteasome inhibitor and endothelin receptor antagonist. It induces apoptosis in lymphoma.</p>

<p>hA3AR agonist 1 is a potent human A 3 adenosine receptor (hA 3 AR) agonist (Ki = 2.40 nM) .</p>

<p>Nolpitantium besilate is a neurokinin-1 receptor antagonist.</p>

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

<p>Burapitant (SSR 240600) is a novel non-peptide tachykinin neurokinin 1 (NK) receptor antagonist with anti-coke oven and antidepressant activity.</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>MRS2179 blocks turkey P2Y1 receptor (Kb 102 nM, pA2 6.99), affects platelet aggregation, and has varying IC50s on P2 receptors.</p>

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

<p>KAG-308: selective EP4 agonist; Ki: 2.57 nM, EC50: 17 nM; suppresses colitis, promotes mucosal healing, inhibits TNF-α.</p>

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

<p>GPR27 agonist-1 (compound I) is a selective agonist for GPR27 with a pEC50 value of 6.34.</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>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>Org 274179-0 is an effective allosteric antagonist of the thyroid-stimulating hormone (TSH) receptor, with an IC50 in the nanomolar range. It fully inhibits TSH (and TSI)-mediated activation of the TSH receptor with minimal impact on the efficacy of TSH. This compound can be utilized in studies of Graves' disease (GD).</p>

<p>Serotonin hydrogen maleate serves as a monoaminergic neurotransmitter and an endogenous 5-HT receptor agonist within the central nervous system (CNS). It also functions as an inhibitor of catechol O-methyltransferase (COMT), exhibiting a Ki value of 44 μM.</p>

<p>Inupadenant (EOS-850) is a selective A2a receptor antagonist, targeting immunosuppression in tumors.</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>LP 12 hydrochloride hydrate: potent, selective 5-HT7 agonist (Ki: 0.13 nM); less affinity for D2, 5-HT1A/2A receptors.</p>

BW A868C is a potent, selective PGD2 antagonist and a BW245C analogue, inert to other prostaglandin receptors.

<p>Rodatristat ethyl is an oral TPH1 inhibitor reducing 5-HT levels &amp; lowering PAH at low doses.</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>CS-0777 is a potent, selective, and orally active S1P1 agonist (sphingosine 1-phosphate receptor modulator).</p>

<p>Dopamine D4 receptor ligand 3 (Compound 16) functions as a dopamine D4 receptor (D4R) antagonist with a pKi of 8.86. In HEK-293T cells, it shows pIC50 values of 5.78, 5.55, and 6.17 for Go, Gi, and βArr2 sensors, respectively. This compound inhibits the activity of human glioma cell lines U87 MG, T98G, and U251 MG, and it induces ROS production and mitochondrial dysfunction in these glioma cells.</p>

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

<p>AM9405: peripheral CB1/5-HT3 agonist, suppresses gut motility, relieves GI disorder symptoms in mice.</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>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>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>Sigma-1 receptor antagonist 6 (Compound 12), a σ1R antagonist, demonstrates significant antiallodynic effects by targeting the Sigma-1 receptor (σ1R). This compound is effective in animal models for neuropathic pain, particularly for reducing mechanical allodynia caused by paclitaxel.</p>

<p>S1P1 agonist 4 exhibits enhanced potency with an EC 50 value of less than 0.05 mg/kg and a predicted human half-life (t1/2) of approximately 5 days, indicating</p>

<p>YM-49598 iodide is a tachykinin NK-1 receptor antagonist. It inhibits drug-induced bladder contractions in rats with an IC50 of 11 μg/kg.</p>

<p>IRL 2500 is an antagonist of Endothelin receptor with IC50s of 1.3 and 94 nM for Endothelin A receptor and Endothelin B receptor.</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>Thielavin B, from Thielavia terricola, inhibits prostaglandin E2 synthesis and reduces rat oedema.</p>

<p>MDMB-FUBICA is a potent agonist of the cannabinoid receptors and exhibits psychoactive properties. It can be utilized in e-cigarettes.</p>

<p>SphK2-IN-2 (21g) is a potent and selective inhibitor of SphK2 (IC50: 0.23 μM).</p>

<p>Nedemelteon is an agonist of the melatonin receptor (melatonin receptor).</p>

<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>BMS-986104 is an effective selective modulator of the S1P1 receptor. It demonstrates efficacy in the mouse EAE model, comparable to that of FTY720. Furthermore, BMS-986104 shows promising remyelination properties in three-dimensional brain cell cultures subjected to lysophosphatidylcholine (LPC)-induced demyelination.</p>

<p>Fosrolapitant is an antagonist of the neurokinin 1 (NK1) receptor.</p>

<p>MRS4833 (compound 15) is an orally active, potent, competitive antagonist of P2Y14R, exhibiting IC50 values of 5.92 nM for hP2Y14R and 4.8 nM for mP2Y14R. It reduces airway eosinophilia in protease-mediated asthma models and reverses chronic neuropathic pain in mouse CCI models.</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>Methacycline, a tetracycline antibiotic, inhibits bacterial protein synthesis and effectively suppresses epithelial-mesenchymal transition (EMT). It blocks EMT in vitro and inhibits fibrogenesis in vivo without directly affecting the TGF-β1Smad signaling pathway. As an antimicrobial agent, Methacycline holds potential for research in pulmonary fibrosis.</p>

<p>UMB24 is an effective antagonist of the σ2 receptor, exhibiting dissociation constants (Ki values) of 170 nM for the σ2 receptor and 322 nM for the σ1 receptor. This compound mitigates cocaine-induced convulsions and hyperactivity without causing mortality.</p>

<p>BMS-741672 is a potent, selective CCR2 antagonist for the treatment of neuropathic pain.</p>

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

<p>L-654284 is an α2-adrenergic receptor antagonist characterized by its notable selectivity. It competes with 3H-clonidine and 3H-rauwolscine for binding in vitro, exhibiting Ki values of 0.8 nM and 1.1 nM, respectively. L-654284 effectively blocks the pre-ejaculatory effects of clonidine in isolated rat vas deferens, with a pA2 value of 9.1. The compound demonstrates significant selectivity for α2 over α1 adrenergic receptors, with a Ki value of 110 nM against 3H-prazosin binding. In vivo, L-654284 significantly increases the turnover of norepinephrine in the rat cerebral cortex, indicating its activity in blocking α2-adrenergic receptors within the central nervous system.</p>

<p>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.</p>

SB 243213 hydrochloride 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).It

<p>Nifeviroc (TD-0232) is an orally active CCR5 antagonist, useful in HIV-1 infection 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>LTD4 antagonist 1 is a potent and orally active antagonist of leukotriene D4 (LTD4; Ki: 0.57 nM).</p>