G-protein Coupled Receptors and 7-TM Receptors

5-HT6R/MAO-B modulator 1 blocks 5-HT6R and permanently inhibits MAO-B, protects glial cells, and reverses memory loss.

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

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

LY 292728 is a highly potent antagonist of leukotriene B4 receptor.

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].

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

GAT564, an allosteric CB1R modulator, shows EC50s of 87 nM (cAMP) & 320 nM (β-arrestin2) and lowers IOP effectively in glaucoma mice.

DMPX (3,7-Dimethyl-1-propargylxanthine) is a caffeine-like compound capable of crossing the blood-brain barrier. It serves as an A2-selective adenosine receptor (AR) antagonist, effectively and selectively blocking the hypothermia and behavioral inhibition induced by A2 adenosine receptor agonists, such as NECA. DMPX is utilized in research on diseases like Parkinson's disease.

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>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>

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].

RU 52583 is an alpha 2-adrenergic receptor antagonist.

SSR-241586: Neurokinin antagonist, treats depression, schizophrenia, urinary issues, emesis, IBS.

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.

BI-44370, a CGRP (calcitonin gene-related peptide) receptor antagonist, can be used to treat migraines and other chronic pain.

inhibitor of human CCR5 binding to HIV-1 gp120

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

<p>Compound 25l, also known as P2Y14R antagonist 4, is an orally active antagonist of the P2Y14R receptor with an IC50 of 5.6 nM. It exhibits higher binding affinity for P2Y14R compared to other PPTN receptors. P2Y14R antagonist 4 also possesses anti-inflammatory properties, reducing the release of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) induced by LPS.</p>

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

DCB-3503, a tylophorine analog, may treat cancer and suppress immunity by blocking protein synthesis and modulating HSC70's ATPase activity.

<p>BRL-37344 is a selective β3-adrenergic receptor agonist. It significantly reduces the body weight of obese mice.</p>

Ro 24-4736 is an effective and selective platelet-activating factor antagonist.

Danavorexton is an orexin receptor agonist.

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

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

GRPR antagonist-1 targets GRPR, kills specific cancer cells (e.g., PC3, Pan02, HGC-27), and promotes apoptosis by modulating Bcl-2 and Bax.

<p>AM9405: peripheral CB1/5-HT3 agonist, suppresses gut motility, relieves GI disorder symptoms in mice.</p>

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

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.

CBR Agonist-1 targets CB1R and CB2R with Ki of 0.18 μM and 1.22 μM, useful for studying cannabinoid-related diseases.

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).

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.

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

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

Potent 5-HT6/5-HT2A receptors dual antagonist with K i of 11 nM & 39 nM.

Nolpitantium besilate is a neurokinin-1 receptor antagonist.

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.

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.

PGD2 is involved in allergy, asthma, sleep, temperature regulation, inhibits clotting, and relaxes blood vessels; PGDM, its metabolite, is a biomarker.

8-iso PGF3α is an isoprostane produced from the free-radical peroxidation of EPA.

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>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>

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.

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

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

BI 639667, an azaindazole-class compound, potently inhibits CCR1 (IC50=1.8 nM in calcium flux assays).

CCR5 antagonist 1 is a CCR5 antagonist extracted from WO 2004054974 A2. It can inhibit HIV replication.

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

CCR3 antagonist2 (example 66) is a CCR3 antagonist useful for researching inflammatory or allergic diseases, particularly those affecting the respiratory tract, such as inflammatory or obstructive airway conditions.

KARI 201 hydrochloride is a selective, brain-penetrant, competitive inhibitor of acid sphingomyelinase (ASM) with an IC50 of 338.3 nM. It also acts as an agonist for the growth hormone-releasing peptide receptor (ghrelin receptor). Additionally, KARI 201 hydrochloride can enhance the neuropathological features of Alzheimer's disease.