GPCR/G Protein

CTCE-0214 is a chemokine CXC receptor 4 (CXCR4) agonist, SDF-1α (stromal cell-derived factor-1α) peptide analog. CTCE-0214 shows anti-inflammatory activity, and can be used in inflammation sepsis and systemic inflammatory syndromes research.

Somatostatin-28 (sheep, human rat mouse) is a biologically active polypeptide, synthesised in the proximal intestinal epithelial cells. Somatostatin-28 (sheep, human rat mouse) suppresses glucose-stimulated insulin secretion without affecting circulating basal insulin concentration. Somatostatin-28 (sheep, human rat mouse) also targets to somatostatin receptor subtype 5 (SSTR5) to regulate GLP-1 secretion.

DOTA-LM3 is a somatostatin receptor (SSTR) antagonist. LM3 refers to p-Cl-Phe- cyclo(D-Cys-Tyr-D-4-amino-Phe(carbamoyl)-Lys-Thr-Cys)D-Tyr- NH2, as well as a somatostatin antagonist. DOTA-LM3 is often isotopically labeled for tracing tumors in vivo, such as 177Lu-DOTA-LM3 and 68 Ga-DOTA-LM3. 68 Ga-DOTA-LM3 shows favorable biodistribution, high tumor uptake, good tumor retention, and few safety concerns. 177Lu-DOTA-LM3 can be used for research in DOTATOC-negative liver metastases, such as pancreatic NET and extensive tumor thrombosis.

Antileukinate, a hexapeptide, is a potent inhibitor of CXC-chemokine receptor (CXCR). Antileukinate inhibits neutrophil chemotaxis and activation. Antileukinate can be used for the research of acute inflammation and injury.

AY254 is an analogue of AY77. AY254 is ERK-biased PAR2 agonist with an EC50 of 2 nM. AY254 relieves cytokine-induced caspase 3/8 activation. AY254 also promotes scratch-wound healing and induced IL-8 secretion via PAR2-ERK1/2 signaling.

R715 is a selective bradykinin B1 receptor antagonist. R715 significantly attenuates the hyperalgesic effect developed in Streptozotocin-diabetic mice.

AY77 is a calcium-biased PAR2 agonist. AY77 shows an EC50 of 0.17 and 2 nM in PAR2-mediated the activation in the Gq pathway and recruitment of β-arrestin-2, respectively. AY77 potently induces intracellular Ca2+ release.

N,N′-Diferuloylputrescine acts as a pigment inhibitor, showing a 57% reduction in pigmentation. It also considerably diminishes the protein expression of MITF and displays potent antioxidant properties as a radical scavenger against reactive oxygen species.

Ornipressin (POR-8) is a vasopressin analog and selective V1 receptor agonist. It is used as a local vasoconstrictor and can effectively reverse hypotension associated with combined general/epidural anesthesia. Ornipressin exhibits antidiuretic activity and, in renal failure models, decreases renal vascular resistance while increasing renal blood flow.

Pimethixene maleate is a potent antihistamine and antiserotonergic compound used as an antimigraine agent. It exhibits strong antagonistic activity at multiple receptors, including serotonin 5-HT1A (pKi 7.63), 5-HT2A (pKi 10.22), 5-HT2B (pKi 10.44), 5-HT2C (pKi 8.42), histamine H1 (pKi 10.14), dopamine D2 (pKi 8.19), dopamine D4.4 (pKi 7.54), muscarinic M1 (pKi 8.61), and muscarinic M2 (pKi 9.38) receptors. Its broad receptor-binding profile contributes to its therapeutic efficacy in migraine management.

Balixafortide (POL6326) is a potent, selective, and well-tolerated peptidic antagonist of the CXCR4 receptor, with IC50 values below 10 nM. It demonstrates over 1000-fold selectivity for CXCR4 compared to other receptors, including CXCR7. Balixafortide effectively blocks β-arrestin recruitment and calcium flux, and is a strong mobilizer of hematopoietic stem and progenitor cells (HSPCs). It also exhibits anti-cancer activity, making it a promising candidate for oncology and hematology research.

Ladarixin (DF 2156A free base) is an orally active, allosteric, non-competitive antagonist of the chemokine receptors CXCR1 and CXCR2. By blocking these receptors, Ladarixin inhibits neutrophil recruitment and inflammatory responses. It is under investigation for the treatment of inflammatory airway diseases such as chronic obstructive pulmonary disease (COPD) and asthma.

LIT-927 is a locally and orally active CXCL12 neutraligand with anti-inflammatory properties. It binds to CXCL12 with a Ki of 267 nM, thereby preventing its interaction with the CXCR4 receptor. LIT-927 is a valuable tool for studying CXCL12/CXCR4-mediated signaling in inflammatory and immune-related conditions.

Calhex 231 hydrochloride is a potent negative allosteric modulator of the calcium-sensing receptor (CaSR), with an IC50 of 0.39 μM for inhibiting \[³H]inositol phosphate accumulation induced by CaSR activation. It transiently blocks signaling through the human wild-type CaSR and is utilized in research related to traumatic hemorrhagic shock (THS) and diabetic cardiomyopathy (DCM), where dysregulated calcium signaling contributes to disease pathology.

AC-265347 is a calcium-sensing receptor (CaSR) agonist and positive allosteric modulator (ago-PAM) with a functional affinity (pK\_B) of 5.1. It enhances CaSR activation and is useful for research into disorders related to calcium metabolism, such as hyperparathyroidism and other CaSR-associated diseases.

Calindol hydrochloride is a positive allosteric modulator (PAM) of the calcium-sensing receptor (CaSR), acting as a calcimimetic compound. It enhances CaSR activation with an EC50 of 132 nM, making it a valuable tool for studying calcium homeostasis and related signaling pathways.

Encaleret (CLTX-305) is an orally active and highly potent antagonist of the calcium-sensing receptor (CaSR), with an IC50 of 0.012 μM. It promotes the secretion of parathyroid hormone (PTH) by inhibiting CaSR activity and is being investigated for the treatment of conditions such as osteoporosis and autosomal dominant hypocalcemia type 1 (ADH1).

Lycoperodine-1 (Cyclomethyltryptophan) is a bioactive compound isolated from tomato fruits (*Lycopersicon esculentum*). It functions as an agonist of calcium-sensing receptors (CaSR), making it a useful molecule for studying CaSR-mediated signaling pathways and calcium homeostasis.

Ronacaleret hydrochloride (SB 751689A) is an orally active, potent, and selective antagonist of the calcium-sensing receptor (CaSR). It stimulates the endogenous release of parathyroid hormone (PTH) from the parathyroid glands, supporting its use in the study of postmenopausal osteoporosis and related metabolic bone disorders.

Ronacaleret (SB 751689) is an orally active, potent, and selective calcium-sensing receptor (CaSR) antagonist that stimulates the endogenous release of parathyroid hormone (PTH) from the parathyroid glands. By modulating calcium homeostasis and enhancing PTH secretion, Ronacaleret is used in the study of postmenopausal osteoporosis and other bone-related metabolic disorders.

TAK-075 is an orally active and highly potent calcium-sensing receptor (CaSR) antagonist with an IC50 of 0.94 nM. It promotes transient parathyroid hormone (PTH) secretion in rats and effectively prevents the sustained suppression of PTH caused by the buildup of active metabolites, thereby preserving normal PTH secretion dynamics. TAK-075 is a valuable compound for research in metabolic bone diseases, including osteoporosis.

Antalarmin hydrochloride is an orally active, non-peptide antagonist of corticotropin-releasing hormone receptor 1 (CRHR1) with a Ki of 1 nM. It effectively suppresses CRH-induced adrenocorticotropic hormone (ACTH) secretion and blocks both CRH- and novelty-induced anxiety-like behaviors in animal models. Antalarmin hydrochloride also exhibits anti-inflammatory activity in arthritis models and alleviates stress-induced gastric ulceration, supporting its potential in research related to irritable bowel syndrome and stress-related inflammatory conditions.

NBI-27914 is a potent and selective antagonist of corticotropin-releasing factor receptor 1 (CRFR1), a member of the G protein-coupled receptor (GPCR) superfamily. By selectively blocking CRFR1, NBI-27914 is useful for studying stress-related pathways and disorders mediated by CRF signaling, such as anxiety and depression.

Urocortin, human, is a 40-amino acid neuropeptide that functions as a selective agonist of the endogenous corticotropin-releasing factor receptor 2 (CRF₂). It exhibits high binding affinity with Kᵢ values of 0.4 nM for human CRF₁, 0.3 nM for rat CRF₂α, and 0.5 nM for mouse CRF₂β. Urocortin plays a role in modulating stress responses, cardiovascular function, and feeding behavior.

JNJ19567470 (R317573) is a selective, non-peptidergic corticotropin-releasing factor type 1 (CRF₁) receptor antagonist. It effectively blocks sodium lactate (NaLac)-induced panic-like behavior and associated cardiovascular responses. JNJ19567470 also reduces regional glucose utilization in the amygdala and attenuates anxiety-related responses

Antalarmin is a selective, nonpeptide antagonist of corticotropin-releasing factor receptor 1 (CRHR1), with a Ki of 2.7 nM. It is capable of crossing the blood–brain barrier, making it a valuable compound for investigating CRHR1-mediated central nervous system functions and stress-related disorders.

α-Helical CRF(9-41) is a competitive antagonist of the corticotropin-releasing factor receptor 2 (CRF₂) with a K\_B of approximately 100 nM. It also acts as a partial agonist at the CRF₁ receptor, with an EC₅₀ of 140 nM. This dual activity makes it a useful tool for studying CRF receptor signaling and stress-related physiological responses.

Tildacerfont is a potent and orally active corticotropin-releasing factor type 1 (CRF1) receptor antagonist. It effectively reduces levels of adrenocorticotropic hormone (ACTH) and adrenal androgens, demonstrating a favorable safety profile. Tildacerfont is being investigated for the treatment of congenital adrenal hyperplasia (CAH) and holds promise for research into disorders of the hypothalamic-pituitary-adrenal (HPA) axis.

C16-PAF (PAF (C16)) is a phospholipid mediator and a potent platelet-activating factor that functions as a ligand for the PAF G-protein-coupled receptor (PAFR). It exhibits anti-apoptotic effects by inhibiting caspase-dependent cell death through PAFR activation. C16-PAF is a strong activator of the MAPK and MEK/ERK signaling pathways and is known to induce increased vascular permeability.

Buspirone is an orally active anxiolytic agent that acts as a partial agonist at 5-HT1A receptors and an antagonist at dopamine D2 autoreceptors. It is commonly used in the research and treatment of generalized anxiety disorder (GAD), offering anxiolytic effects without the sedative or dependence-forming properties of benzodiazepines.

AL-8810 is a potent and selective antagonist of the prostaglandin F2α (PGF2α) receptor (FP receptor), with Ki values of 0.2 ± 0.06 μM in mouse 3T3 cells and 0.4 ± 0.1 μM in rat A7r5 cells. In addition to its antagonistic activity, AL-8810 also activates MAPK and ERK1/2 signaling pathways. It is commonly used in research related to elevated intraocular pressure (OHT) and primary open-angle glaucoma (POAG).

CDPPB is a selective, orally active allosteric modulator of the metabotropic glutamate receptor 5 (mGluR5). It enhances AKT and ERK1/2 signaling and upregulates BDNF mRNA expression. CDPPB also inhibits caspase-3 activation and mitigates mitochondrial dysfunction, demonstrating therapeutic potential in improving cognitive impairment, depression, and Huntington’s disease.

I-287 is an orally active and selective protease-activated receptor 2 (PAR2) inhibitor that functions as a negative allosteric modulator, specifically targeting Gαq and Gα12/13 signaling pathways and their downstream effectors. By disrupting PAR2-mediated signaling, I-287 effectively reduces inflammation in preclinical models, including Complete Freund's Adjuvant (CFA)-induced inflammation in mice.

Fenoprofen (LILLY-53858) is a nonsteroidal anti-inflammatory drug (NSAID) that functions primarily by inhibiting cyclooxygenase (COX) enzymes, thereby reducing the synthesis of pro-inflammatory prostaglandins. In addition to its classical NSAID activity, Fenoprofen has been identified as a positive allosteric modulator (PAM) of melanocortin receptors (MCRs), enhancing MCR-mediated signaling. Fenoprofen also promotes ERK1/2 activation in HEK293T cells, suggesting additional modulation of intracellular signaling pathways involved in inflammation and cellular proliferation.

Firazorexton (TAK-994 free base) is an orally active, brain-penetrant, and highly selective agonist of the orexin type 2 receptor (OX2R). By activating OX2R, Firazorexton enhances wakefulness and has demonstrated efficacy in preclinical models, notably improving narcolepsy-like symptoms in mice. Its targeted action on the orexin system positions it as a promising therapeutic candidate for sleep disorders such as narcolepsy and excessive daytime sleepiness.

4′-Demethylnobiletin is a bioactive metabolite derived from citrus polymethoxyflavones, known for its neuroprotective and cognition-enhancing properties. It activates the PKA/ERK/CREB signaling pathway and enhances CRE (cAMP response element)-mediated transcription in hippocampal neurons, processes essential for synaptic plasticity and memory formation. Additionally, 4′-Demethylnobiletin reverses memory impairment caused by NMDA receptor antagonism by stimulating ERK signaling, highlighting its therapeutic potential for neurodegenerative diseases and cognitive dysfunction.

Firazorexton hydrate (TAK-994) is an orally active, brain-penetrant selective agonist of the orexin type 2 receptor (OX2R). It effectively promotes wakefulness by stimulating OX2R signaling, which plays a critical role in regulating the sleep–wake cycle. In preclinical studies, Firazorexton hydrate has demonstrated the ability to alleviate narcolepsy-like symptoms in mouse models, making it a promising therapeutic candidate for sleep disorders such as narcolepsy and excessive daytime sleepiness.

Brophenexin (compound 8) is a potent inhibitor of the interaction interface between NMDA receptors (NMDAR) and TRPM4 channels, exhibiting significant neuroprotective activity. It prevents NMDA-induced excitotoxicity, including cell death and mitochondrial dysfunction in hippocampal neurons, with an IC₅₀ of 2.1 μM. In vivo, Brophenexin protects against brain damage in mice subjected to middle cerebral artery occlusion (MCAO) and preserves retinal ganglion cells from NMDA-induced degeneration. These findings support its potential as a therapeutic agent for neurodegenerative diseases and ischemic brain injury.

Chemerin-9 (149–157) TFA is a potent peptide agonist of chemokine-like receptor 1 (CMKLR1), exhibiting significant anti-inflammatory activity. It activates downstream signaling pathways by stimulating the phosphorylation of Akt and ERK and promoting reactive oxygen species (ROS) production. Chemerin-9 (149–157) TFA has demonstrated neuroprotective effects, including the amelioration of Aβ₁₋₄₂-induced memory impairment in Alzheimer's disease models. Additionally, it plays important roles in modulating immune responses, regulating adipocyte differentiation, and improving glucose metabolism, making it a valuable tool for research in inflammation, neurodegeneration, and metabolic disorders.

KR-39038 is a potent and orally bioavailable inhibitor of G protein-coupled receptor kinase 5 (GRK5), with an IC₅₀ of 0.02 μM. It effectively suppresses angiotensin II–induced cellular hypertrophy by inhibiting the HDAC5 signaling pathway in neonatal cardiomyocytes. KR-39038 exhibits strong anti-hypertrophic activity and improves cardiac function in preclinical models, making it a promising candidate for research in heart failure and related cardiovascular diseases.

Oleuropein Aglycone (3,4-DHPEA-EA) is a bioactive polyphenol and the aglycone form of oleuropein, generated through enzymatic, acidic, or acetylated hydrolysis. It exhibits a broad range of pharmacological effects. In a TgCRND8 transgenic mouse model of Alzheimer’s disease, dietary supplementation (50 mg/kg) increases neuronal autophagic vesicles, reverses cognitive deficits, and reduces histone deacetylase 2 (HDAC2) levels in the cortex and hippocampus. In a high-fat diet-induced obesity rat model, Oleuropein Aglycone elevates urinary norepinephrine, interscapular brown adipose tissue epinephrine, and UCP1 protein levels, while reducing plasma leptin levels and total abdominal fat mass. Additionally, in a carrageenan-induced pleurisy mouse model, it mitigates lung neutrophil infiltration, lipid peroxidation, and IL-1β production. These findings highlight its potential in neurodegenerative, metabolic, and inflammatory disease research.

AG-825 is a selective, ATP-competitive inhibitor of ErbB2 (HER2) tyrosine kinase, with an IC₅₀ of 0.35 μM. It exhibits both anticancer and anti-inflammatory activities and has been shown to significantly accelerate apoptosis in human neutrophils. AG-825 also increases β₁-adrenergic receptor (β₁AR) density, suggesting potential cardiomodulatory effects. Due to its multifaceted biological activity, AG-825 is a valuable compound for research in oncology, inflammation, and cardiovascular disease.

AR420626 is a selective agonist of free fatty acid receptor 3 (FFAR3, also known as GPR41), with an IC₅₀ of 117 nM. It demonstrates anti-inflammatory, antitumor, and antidiabetic activities. AR420626 improves neurogenic diarrhea by modulating neural pathways mediated by nicotinic acetylcholine receptors (nAChRs). In cancer models, it suppresses the growth of HepG2 xenografts and inhibits hepatoma cell proliferation through apoptosis induction. Additionally, AR420626 mitigates allergic asthma and eczema and enhances glucose uptake by activating FFAR3-mediated Ca²⁺ signaling, offering potential therapeutic benefits in metabolic disorders such as diabetes.

Glepaglutide (ZP1848) is a long-acting glucagon-like peptide-2 (GLP-2) analogue and a potent agonist of the GLP-2 receptor (GLP-2R). It enhances intestinal absorption, reduces faecal output, and alleviates small intestinal inflammation. Glepaglutide is a valuable agent for research in inflammatory bowel disease (IBD), including Crohn’s disease.

1-Oleoyl lysophosphatidic acid sodium is a potent LPA receptor activator, functioning primarily as a bioactive phospholipid. This compound promotes mitosis by inducing DNA synthesis, making it critical for studies in cell proliferation. Additionally, 1-Oleoyl lysophosphatidic acid sodium plays a role in mediating both normal and pathological emotional responses, including anxiety and depression, contributing to research in neurobiology and mental health disorders.

RTIOXA-43 is an orexin receptor agonist that exhibits potent activity with EC50 values of 24 nM for both OX1 and OX2 receptors. This compound is valuable for research applications related to sleep regulation, appetite control, and energy metabolism. By activating orexin receptors, RTIOXA-43 facilitates investigations into neurodegenerative diseases and sleep disorders.

N-Arachidonylglycine (NA-Gly) selectively acts as an agonist for the GPR18 receptor, exhibiting an EC50 value of 44.5 nM. Unlike its structural analog anandamide, NA-Gly does not engage with CB1 or CB2 receptors. This compound also demonstrates inhibitory activity on GLYT2 with an IC50 of 5.1 μM. Additionally, N-Arachidonylglycine has been shown to effectively promote the migration of endometrial cells, making it a valuable tool for research in cellular migration and cannabinoid receptor activity.

Propranolol hydrochloride is a nonselective β-adrenergic receptor antagonist that effectively crosses the blood-brain barrier. It exhibits high affinity for both β1AR and β2AR receptors, with Ki values of 1.8 nM and 0.8 nM, respectively, and inhibits [3H]-DHA binding in rat brain membranes with an IC50 of 12 nM. This reagent is widely used in research related to hypertension, pheochromocytoma, myocardial infarction, cardiac arrhythmias, angina pectoris, and hypertrophic cardiomyopathy.

Indoramin is an orally active antihypertensive agent targeting the α1A-adrenoceptor. This compound works by selectively blocking α1-adrenoceptors, leading to vasodilation and a reduction in blood pressure. Indoramin is utilized in cardiovascular research to study blood pressure regulation and the mechanisms of hypertension.

GSA-10 is a potent agonist of the smooth (Smo) receptor, playing a crucial role in mediating Hedgehog (Hh) signaling pathways. This compound exhibits significant osteogenic activity and is valuable in regenerative medicine and research on cancer pathologies. Additionally, GSA-10 can be utilized in studies focused on adipogenesis and fat development, making it a versatile tool in biological research.