g protein-coupled receptors

CID 2745687 is a moderately potent, concentration-dependent antagonist at human GPR35 with pIC50 = 6.70. CID 2745687 cannot effectively antagonize the agonist effects of either Zaprinast or Cromolyn disodium at rodent ortholog of GPR35 in vitro[1]. However, CID 2745687 can reverse lodoxamide-mediated anti-fibrotic effects in mice in vivo[2].

Sphingosine-1-phosphate (S1P) is an agonist for S1P1-5 receptors and a ligand for GPR3, GPR6, and GPR12. As an intracellular second messenger, it mobilizes Ca2+ and acts as an extracellular ligand for G-protein coupled receptors. This important lipid mediator is generated from sphingosine or other membrane phospholipids.

Higenamine hydrochloride (norcoclaurine HCl) has been demonstrated to be a β2 adrenoreceptor agonist. Adrenergic receptors, or adrenoceptors, belong to the class of G protein–coupled receptors, and are the most prominent receptors in the adipose membrane, besides also being expressed in skeletal muscle tissue.

MS67 is a potent and selective degrader of WD40 repeat domain protein 5 (WDR5) with a dissociation constant (Kd) of 63 nM, exhibiting no activity against protein methyltransferases, kinases, G-protein-coupled receptors (GPCRs), ion channels, and transporters, and notably demonstrating significant anticancer properties.

N-phenylthiophene-2-carboximidamide is a thiophene derivative that functions as an inhibitor of protein tyrosine kinases (PTKs) and a ligand for G protein-coupled receptors (GPCRs).

Vasopressin acetate, a cyclic nonapeptide, is synthesized centrally in the hypothalamus. Vasopressin acetate acts as a neurotransmitter, exerting its action by binding to specific G protein-coupled receptors.

Protein Kinase C Peptide Substrate acetate targets specific cell spacers ina manner that is dependent on second messengers and specific adaptor proteins in response to extracellular signals that activate g protein-coupled receptors, tyrosine Kinase recept

BAM (8-22) acetate is a proteolytically cleaved product of proenkephalin A. BAM (8-22) acetate activates Mas-related G-protein-coupled receptors (Mrgprs), MrgprC11 and hMrgprX1, and induces scratching in mice in an Mrgpr-dependent manner.

Anandamide ((5Z,8Z,11Z,14Z)-N-(2-Hydroxyethyl)icosa-5,8,11,14-tetraenamide), an immune modulator, acts via not only cannabinoid receptors (CB1 and CB2) but also other targets (e.g., GPR18 GPR55) in the central nervous system.

1-Stearoyl-sn-glycerol 3-phosphate sodium, a biologically active phospholipid, plays a crucial role in regulating cell motility, proliferation, invasion, survival, and the production of growth factors through interactions with G protein-coupled receptors (GPCR). Synthesized during the formation of membrane phospholipids, this compound typically has a low plasma concentration (approximately 100nM) and originates from various cell types, including activated platelets, epithelial cells, leukocytes, neuronal cells, and tumor cells. Its distinctive structure features stearic acid at the sn-1 position and a hydroxyl group at the sn-2 position.

Vasopressin-d5 TFA is the TFA salt form of Vasopressin-d5, an isotopically labeled derivative of Vasopressin. Vasopressin, a cyclic nonapeptide, is synthesized in the medial hypothalamus and plays a critical role in the hypothalamic-pituitary-adrenal axis by enhancing the stimulation of corticotropin-releasing factor, thereby regulating the secretion of adrenocorticotropic hormone. Additionally, Vasopressin acts as a neurotransmitter, exerting its effects through interaction with specific G-protein-coupled receptors.

AB-FUBICA (Compound 13) is a CB1 and CB2 receptor agonist that activates G protein-coupled inwardly-rectifying potassium channels (GIRK) through binding to CB1 and CB2 receptors, demonstrating significant cannabinoid-like activity. Its EC50 values are 21 nM for CB1 and 15 nM for CB2. AB-FUBICA may be applicable for research in pain management, neurodegenerative diseases, and inflammation-related mechanisms.

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.

Somatostatin RC 102 is a peptide hormone. It regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G protein-coupled somatostatin receptors and inhibition of the release of numerous secondary hormones.

SPM-242 is an orthosteric agonist of Sphingosine 1-phosphate (S1P) and a bitopic antagonist. S1P is a lysophospholipid signaling molecule that regulates important biological functions, including vascular development and lymphocyte trafficking, by activat

Kisspeptin-54 is a peptide ligand of the orphan G protein-coupled receptor GPR54 (Kis = 1.81 and 1.45 nM for rat and human receptors, respectively).1 It is a 54 amino acid peptide encoded by the metastasis suppressor gene KISS-1. Kisspeptin-54 induces calcium mobilization in CHO-K1 cells expressing rat and human receptors (EC50s = 1.39 and 5.47 nM, respectively). It also induces arachidonic acid release in CHO cells expressing rat and human GPR54 in a concentration-dependent manner. Kisspeptin-54 (10-1,000 nM) inhibits insulin secretion from isolated mouse pancreatic β-cells in the presence of 2.8 mM, but not 11.1 mM, glucose.2 Kisspeptin-54 (1-5 nmol, i.c.v.) increases serum levels of luteinizing hormone (LH) and follicular stimulating hormone (FSH) in mice, an effect which is reversed by the gonadotropin releasing hormone (GNRH) antagonist acycline.3References1. Kotani, M., Detheux, M., Vandenbogaerde, A.L., et al. The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54. J. Biol. Chem. 276(37), 34631-34636 (2001).2. Vikman, J., and Ahrén, B. Inhibitory effect of kisspeptins on insulin secretion from isolated mouse islets. Diabetes Obes. Metab. 11(Suppl 4), 197-201 (2009).3. Gottsch, M.L., Cunningham, M.J., Smith, J.T., et al. A role for kisspeptins in the regulation of gonadotropin secretion in the mouse. Endocrinology 145(9), 4073-4077 (2004). Kisspeptin-54 is a peptide ligand of the orphan G protein-coupled receptor GPR54 (Kis = 1.81 and 1.45 nM for rat and human receptors, respectively).1 It is a 54 amino acid peptide encoded by the metastasis suppressor gene KISS-1. Kisspeptin-54 induces calcium mobilization in CHO-K1 cells expressing rat and human receptors (EC50s = 1.39 and 5.47 nM, respectively). It also induces arachidonic acid release in CHO cells expressing rat and human GPR54 in a concentration-dependent manner. Kisspeptin-54 (10-1,000 nM) inhibits insulin secretion from isolated mouse pancreatic β-cells in the presence of 2.8 mM, but not 11.1 mM, glucose.2 Kisspeptin-54 (1-5 nmol, i.c.v.) increases serum levels of luteinizing hormone (LH) and follicular stimulating hormone (FSH) in mice, an effect which is reversed by the gonadotropin releasing hormone (GNRH) antagonist acycline.3 References1. Kotani, M., Detheux, M., Vandenbogaerde, A.L., et al. The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54. J. Biol. Chem. 276(37), 34631-34636 (2001).2. Vikman, J., and Ahrén, B. Inhibitory effect of kisspeptins on insulin secretion from isolated mouse islets. Diabetes Obes. Metab. 11(Suppl 4), 197-201 (2009).3. Gottsch, M.L., Cunningham, M.J., Smith, J.T., et al. A role for kisspeptins in the regulation of gonadotropin secretion in the mouse. Endocrinology 145(9), 4073-4077 (2004).

C16 Lactosylceramide is an endogenous bioactive sphingolipid. It forms membrane microdomains with Lyn kinase and the αi subunits of inhibitory G protein-coupled receptors (GPCRs), suggesting a role in cell signaling. Plasma levels of C16 lactosylceramide are elevated in insulin-resistant cattle. C16 Lactosylceramide is also upregulated in a mouse model of Niemann-Pick type C1 disease, a neurodegenerative cholesterol-sphingolipid lysosomal storage disorder.

Prostaglandin E2 activates four distinct G protein-coupled receptors, EP1-4. Rivenprost is a potent and selective agonist for the EP4 receptor (Ki = 0.7, 56, 620, and >10,000 nM for EP4, EP3, EP2, and EP1, respectively). It has been used to promote EP4-mediated bone formation, prevent bone loss related to osteoporosis, drive osteoblast differentiation, and stabilize bone implants.[1][2][3][4][5] Rivenprost has also been used to support wound healing.[6]

RWJ-56110 dihydrochloride is a potent, selective, peptide-mimetic inhibitor of PAR-1 activation and internalization (binding IC50=0.44 μM), showing no effect on PAR-2, PAR-3, or PAR-4. It inhibits the aggregation of human platelets induced by SFLLRN-NH2 (IC50=0.16 μM) and thrombin (IC50=0.34 μM), with high selectivity relative to U46619. RWJ-56110 dihydrochloride also blocks angiogenesis and the formation of new vessels in vivo, and induces cell apoptosis[1][2].

12(S)-HETrE is an endogenous metabolite produced by oxidation of ω-6 PUFA dihomo-γ-linolenic acid (DGLA) by 12-lipoxygenase (12-LOX) in platelets, which acts on Gαs-coupled G-protein-coupled receptors, has antithrombotic properties, and has potential therapeutic use in cardiovascular disease. 12(S)-HETrE is reported to inhibit agonist-mediated platelet activation (IC50 = 40 μM), α granule secretion, integrin αIIbβ3 activation, Rap1 activation, and thrombin-induced clot retraction in vitro.

1-Oleoyl Lysophosphatidic Acid (1-Oleoyl LPA) is a biologically active phospholipid that can exert multiple biological effects in various disease states of the kidney by activating a complex network of at least six homologous G protein-coupled receptors and their heterotrimeric G proteins. 1-Oleoyl Lysophosphatidic Acid promotes polarization of BV-2 and primary murine microglia toward an M1-like phenotype and can be used to study cancer and atherosclerosis.

CXCR3 antagonist 6c is an antagonist of chemokine (C-X-C motif) receptor 3 (CXCR3).1It inhibits calcium mobilization induced by chemokine (C-X-C motif) ligand 11 (CXCL11) in HEK293 cells expressing the human receptor (IC50= 0.06 μM). It is selective for CXCR3 over a panel of 14 human G protein-coupled receptors at 10 μM. CXCR3 antagonist 6c inhibits CXCR3-mediated migration of isolated human T cells (IC50= ~100 nM). 1.Cole, A.G., Stroke, I.L., Brescia, M.-R., et al.Identification and initial evaluation of 4-N-aryl-[1,4]diazepane ureas as potent CXCR3 antagonistsBioorg. Med. Chem. Lett.16(1)200-203(2006)

Lysosphingomyelin is an endogenous bioactive sphingolipid and a constituent of lipoproteins.1,2It is produced by the removal of the acyl group from sphingomyelin by a deacylase and acts as a precursor in the biosynthesis of sphingosine-1-phosphate . D-erythroLysosphingomyelin is an agonist of the S1P receptors S1P1, S1P2, and S1P3(EC50s = 167.7, 368.1, and 482.6 nM, respectively, for the human receptors).3It is also an agonist of the orphan receptor ovarian cancer G protein-coupled receptor 1 (ORG1) that induces calcium accumulation in cells overexpressing OGR1 (EC50= ~35 nM).4Levels of D-erythrolysosphingomyelin are increased in skin isolated from patients with atopic dermatitis, as well as postmortem brain from patients with Niemann-Pick disease type A, but not type B.2,5L-threolysosphingomyelin is also an S1P1-3agonist (EC50s = 19.3, 131.8, and 313.3 nM, respectively).3This product is a mixture of D-erythroand L-threolysosphingomyelin. [Matreya, LLC. Catalog No. 1321] 1.Ito, M., Kurita, T., and Kita, K.A novel enzyme that cleaves the N-acyl linkage of ceramides in various glycosphingolipids as well as sphingomyelin to produce their lyso formsJ. Biol. Chem.270(41)24370-24374(1995) 2.Nixon, G.F., Mathieson, F.A., and Hunter, I.The multi-functional role of sphingosylphosphorylcholineProg. Lipid Res.47(1)62-75(2008) 3.Im, D.-S., Clemens, J., Macdonald, T.L., et al.Characterization of the human and mouse sphingosine 1-phosphate receptor, S1P5 (Edg-8): Structure-activity relationship of sphingosine1-phosphate receptorsBiochemistry40(46)14053-14060(2001) 4.Meyer zu Heringdorf, D., Himmel, H.M., and Jakobs, K.H.Sphingosylphosphorylcholine-biological functions and mechanisms of actionBiochim. Biophys. Acta1582(1-3)178-189(2002) 5.Rodriguez-Lafrasse, C., and Vanier, M.T.Sphingosylphosphorylcholine in Niemann-Pick disease brain: Accumulation in type A but not in type BNeurochem. Res.24(2)199-205(1999)

1-Palmitoyl lysophosphatidic acid (1-Palmitoyl LPA) is a LPA analog containing palmitic acid at the sn-1 position. LPA binds to one of five different G protein-coupled receptors (GPCRs) to mediate a variety of biological responses including cell proliferation, smooth muscle contraction, platelet aggregation, neurite retraction, and cell motility. In addition to playing a role in the aforementioned biological responses, 1-palmitoyl LPA enhances the action of β-lactam antibiotics (ampicillin, piperacillin, and ceftazidime) on various strains of Pseudomonas aeruginosa, a pathogen associated with pulmonary disease and pneumonia, via binding both Ca2+ and Mg2+.