G-protein Coupled Receptors and 7-TM Receptors

inhibitor of human CCR5 binding to HIV-1 gp120

RU 52583 is an alpha 2-adrenergic receptor antagonist.

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

<p>(R)-MrgprX2 antagonist-3 is an antagonist of MrgprX2. It is applicable in the study of inflammatory skin diseases. For more detailed information, please refer to compound E118 in patent document WO2021092240A1.</p>

PAR4 antagonist3 (Compound 36) is a selective antagonist of protease-activated receptor 4 (PAR4). It exhibits antiplatelet activity with an IC50 of 26.1 nM and enhances metabolic stability in human liver microsomes, with a half-life (T1/2) of 97.6 minutes.

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

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

<p>AMG-369 (AMG 247) is an S1P1/S1P5 dual agonist that delays the development of experimental autoimmune encephalomyelitis in rats.</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.

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>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>GRKs-IN-1 has remarkable potency against and selectivity for G protein-coupled receptor kinase 2 GRK2 (IC50: 130 nM) and GRK5 (IC50: 7.1 μM).</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>Compound 10o, a histamine H3 antagonist-1, functions as both a histamine H3 antagonist and a serotonin reuptake inhibitor, making it useful for research in depression [1].</p>

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

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>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>

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

CCR1 antagonist13 is a selective small molecule antagonist of CCR1.

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

<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>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>

(2R,3S)-N-(4-(2,6-dimethoxyphenyl)-5-(5-methylpyridin-3-yl)-4H-1,2,4-triazol-3-yl)-3-(5-methylpyrimidin-2-yl)butane-2-sulfonamide is an Apelin receptor agonist

<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>

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.

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].

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

GLP-1 Receptor Agonist 11 (compound 3) acts as an effective agonist for the GLP Receptor, finding use in research related to conditions like diabetes and non-alc. fatty liver disease [1].

CVN766 is an orally active orexin 1 receptor antagonist with blood-brain permeability, demonstrating IC50 values of 8 nM for OX1R and >10 μM for OX2R. CVN766 can be used to study schizophrenia [1].

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].

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].

EP-3945 is an agonist of Mas-related G protein-coupled receptors (MRGPR), exhibiting greater potency than the small molecule agonist β-Alanine targeting MRGPRD. MRGPRs play a crucial role in inflammatory itch and pain perception. These receptors interact with Gq (MRGPRX2, MRGPRX4, and MRGPRX1 are coupled with Gq; MRGPRX2 and MRGPRD couple with Gi), with EP-3945 having an EC50 value of 211.6 nM for Gq.

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

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

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].

RGH-122 (compound 43), characterized as an orally active, potent, and selective hV1a receptor antagonist, demonstrates significant affinity with a K i value of 0.3 nM and an IC 50 of 0.9 nM. It exhibits microsomal stability, indicated by a CL int value of 13/28/25 μL/min/mg [1].

Tebideutorexant, an orexin-1 receptor antagonist, shows anti-panic effects in rodents and humans, providing a tool for stress response and psychiatric research.

Iralukast is a cysteinyl-leukotriene antagonist (CysLT) with a pKi of 7.8 for CysLT1.

BIBO3304 (diTFA), a selective neuropeptide Y (NPY) Y1 receptor antagonist, demonstrates oral efficacy. It exhibits high affinity for Y1 receptors in both humans and rats, with IC50 values of 0.38 nM and 0.72 nM, respectively. Additionally, BIBO3304 (diTFA) enhances bone-tendon healing via the Wnt/β-catenin signaling pathway [1] [2] [3].

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

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

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

Compound 13 is a PAR-1 antagonist with a 3 nM IC50, useful for thrombosis and heart disease research.

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

Aeruginosin 98-B, a protease inhibitor, effectively inhibits trypsin, plasmin, and thrombin with IC50 values of 0.6, 7.0, and 10.0 μg/mL, respectively.

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

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

GLP-1R agonist 33 (Compound 224) is a GLP-1 receptor agonist with potential applications in research related to diabetes, obesity, and non-alcoholic fatty liver disease (NAFLD).

<p>K-8794 is an orally active and selective endothelin receptor ETB antagonist that can be utilized in cardiovascular disease research.</p>

<p>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).</p>

N-methyl LTC4 is a stable synthetic analog of LTC4 and a selective CysLT2 agonist, useful in studying leukotriene pharmacology.

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

<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>

BER-5 is a potent MrgX2 antagonist, demonstrating broad-spectrum antagonistic activity against various MrgX2 agonists. It can inhibit Substance P(SP)-induced degranulation in LAD2 cells and alleviate SP-induced allergic reactions in mice. BER-5 is useful for researching mechanisms related to allergic reactions.

<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>

RXFP1 receptor agonist-9 is a potent RXFP1 agonist with an EC50 value of 2.5 μM and a Ymax of 65%. This compound exhibits significant microsomal stability, desirable pharmacokinetic properties, and pharmacodynamic activity. RXFP1 receptor agonist-9 is useful in the study of heart failure.

PSB-KK1415 is a selective agonist for the human orphan G protein-coupled receptor GPR18, with an EC50 of 19.1 nM.

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

NPRA agonist-11 (Example 161) is an NPRA (NPR1) agonist with AC50 values of 1.681 μM and 0.989 μM for human and monkey, respectively. It is applicable in research on cardiovascular and other diseases.

CTW0404 is an effective positive allosteric modulator (PAM) of the 5-HT receptor, with promising implications for research into neuropsychiatric disorders.

2,3-MDMA hydrochloride is an inhibitor of the noradrenalin transporter and serotonin transporter, with IC50 values of 6.2 μM and 82 μM, respectively.

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

5-HT2A receptor agonist-8 (compound 8) is a potent 5-HT2A receptor agonist with an EC50 of 0.6784 nM. It is suitable for research related to depression and bipolar disorder.

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

OX2R agonist 1 is an OX2R activator with an EC50 of less than 100 nM. It is utilized in research related to narcolepsy and cataplexy.

LTB4 is a leukocyte-activating fatty acid via 5-lipoxygenase. Two receptors, BLT1 and BLT2, bind it. 14,15-dehydro LTB4 is a stronger BLT1 antagonist.

Sp-UTP-α-S serves as an activator of P2Y2 and P2Y4 receptors and is applicable in cancer research.

Cannabigerovarin (CBGV) is a compound categorized as a phytocannabinoid.

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

Jimscaline (compound R-(-)2) is a 5-HT2A agonist and a mescaline analogue, used in neuroscience research.

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

PD-147693 (compound II) is an active metabolite of the presynaptic dopamine autoreceptor agonist CI-1007, and it exhibits antipsychotic activity similar to CI-1007.

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

DNA crosslinker 6 (compound 1) is an anti-mitotic agent known for its strong binding affinity to AT-DNA and inhibition of AT-hook 1 binding to DNA (IC50=0.03 µM). Additionally, it exhibits anti-protozoal activity, effectively inhibiting T. brucei with an EC50 of 0.83 µM.

GLP-1 Receptor Agonist 10 (Compound 42), an agonist of the GLP receptor, reduces glucose excursions and inhibits food intake in mice. It is useful for research into type 2 diabetes (T2DM) and obesity [1].

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

RWJ-68022 (Example 9) is a cyclopentene derivative that serves as a motilin receptor antagonist. It competes with motilin and erythromycin at motilin receptor sites and is applicable in research on gastrointestinal disorders.

MRGPRX2 modulator-3 (Compound 4-400) is a quinoline derivative and an MRGPRX2 regulator. It is utilized in the investigation of MRGPRX2-related conditions, including allergies, itching, pain, inflammation, and autoimmune diseases.

GPR183 inverse agonist-1 (Compound 78) is an inverse agonist of GPR183. It inhibits GPR183-mediated Gi activation and β-arrestin2 recruitment while blocking PBMC migration. This compound is utilized in research concerning inflammation, autoimmune, and cancer-related diseases.

SLF1081851 (hydrochloride), a Spns2 inhibitor, effectively inhibits S1P release with an IC50 value of 1.93 μM. This compound is instrumental in the development and functioning of the immune system [1].

SSR 146977 hydrochloride is a potent, selective antagonist of the tachykinin NK 3 receptor, and it can be utilized in research on psychiatric disorders and airway inflammation [1].

(+)-15-epi Cloprostenol is a synthetic analogue of prostaglandin F2α (PGF2α) and functions as a potent FP receptor agonist. The compound (+)-15-epi Cloprostenol is the 15(S) or 15β-hydroxy enantiomer of (+)-(+)-15-epi Cloprostenol. Compared to the 15(R)-(+)-15-epi Cloprostenol, this epimer exhibits significantly lower activity as an FP receptor ligand. However, the specific activity of this isomer remains inadequately studied.

LPA5 antagonist 3 (Example 74), a lysophosphatidic acid receptor 5 (LPA5) antagonist, exhibits potent activity with an IC50 value of 170 nM. It is primarily utilized in the research of pain disorders and atherosclerosis [1].

25C-NBF hydrochloride is an agonist of 5-HT receptors, specifically activating 5-HT2A and 5-HT2C receptors, with an EC50 of approximately 0.3 μM.

GLP-1R modulator-1 (Compound 384) is a potent and orally active selective agonist of the glucagon-like peptide-1 receptor (GLP-1R). It activates G protein-coupled signaling, leading to increased intracellular cAMP levels, enhanced insulin secretion, delayed gastric emptying, and reduced appetite. GLP-1R modulator-1 holds potential for research in type 2 diabetes, obesity, and non-alcoholic steatohepatitis (NASH).

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.

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>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>

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.

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

VU0514009 is a competitive antagonist of chemokine-like receptor 1 (CMKLR1) with an EC50 of 2 nM. It effectively inhibits chemerin-9-induced arrestin recruitment and receptor internalization, significantly reducing Ca2+ flux responses in HEK293 cells. This compound shows potential for research in inflammatory diseases and metabolic syndrome.

Iloprost, a potent prostacyclin analog, binds to human IP & EP1 receptors with high affinity; inhibits platelet aggregation effectively.

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.

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.

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.