G-protein Coupled Receptors and 7-TM Receptors

BMS-986104 is a potent and selective S1P1 receptor modulator.

<p>NCATS-SM4420 (Compound A35) is an orally effective ligand for the thyroid-stimulating hormone receptor (TSHR) that inhibits the proliferation of MDA-T32 and MDA-T85 cells both in vitro and in vivo, with IC50 values of 0.71 μM and 0.38 μM, respectively. Additionally, it suppresses the metastasis of MDA-T85F1 in mice. NCATS-SM4420 holds potential for research in the field of thyroid cancer.</p>

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

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

<p>AAZ-A 154 mesylate mesylate is a selective, competitive, and non-hallucinogenic antagonist of 5-HT2AR. It enhances neuronal growth in rodents and produces enduring beneficial behavioral effects.</p>

<p>Toladryl is a derivative of Diphenhydramine that can cross the blood-brain barrier and exhibits oral activity, with antihistamine and anticholinergic properties. Its anticholinergic effects are approximately a tenth of those seen with Diphenhydramine, yet it offers 2-4 times the protection against lethal doses of histamine in guinea pigs. The side effects of Toladryl are fewer and milder compared to Diphenhydramine; however, at higher doses, it may cause symptoms such as insomnia, agitation, and disorientation related to the central nervous system. Toladryl is utilized in the research of allergic diseases.</p>

CP-199330: non-toxic alternative to Zafirlukast & Pranlukast, blocks cysteyl LT1 receptors.

Potent CB1/2 agonist 1; crosses blood-brain barrier; anti-inflammatory, analgesic; for multiple sclerosis research.

GPBAR1-IN-3 (Compound 14) is both a selective agonist for GPBAR1, with an EC50 value of 0.17 μM, and an antagonist for CysLT1R [1].

Terguride: treats hyperprolactinemia, blocks 5-HT2A/B, activates dopamine receptors, studied for PAH.

<p>LY210073 is an antagonist of the Leukotriene B4 (LTB4) receptor (IC50: 6.2 nM).</p>

MK-0812 is a dual antagonist of the CCR2 and CCR5 receptors that can alleviate adipose inflammation in ob/ob mice.

ZK118182 isopropyl ester is a PG analog with potent DP-agonist activity (EC50 = 16.5 nM) and high affinity for the DP receptor (Ki = 74 nM).

U75302 is an antagonist of thymosin beta-4 (TB4) receptor with a Ki value of 159 nM on guinea pig lung membranes.

AL-8810 is an 11β-fluoro analog of PGF 2α with selective antagonist effects at the PGF 2α receptor (FP receptor) [1].

SB-423557 is an orally active antagonist of calcium-sensing receptor (CaR) with IC50 of 520 nM

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

RS 61756-007 is a selective thromboxane receptor (TP) agonist.

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

BIIE-0246: A potent, non-peptide Y2 receptor antagonist; >650-fold more selective than Y1, Y4, Y5.

L-796778 acetate is a selective sst3 receptor agonist. In CHO-K1 cells expressing hsst3 receptors, it acts as a partial agonist that inhibits Forskolin-induced cAMP production, with an IC50 value of 18 nM. Additionally, L-796778 acetate exhibits anticonvulsant properties.

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

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].

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].

UK 432097 is an adenosine A2A agonist.

IRL 2500 is an antagonist of Endothelin receptor with IC50s of 1.3 and 94 nM for Endothelin A receptor and Endothelin B receptor.

Danavorexton is an orexin receptor agonist.

<p>EP4 receptor agonist 3 is an activator of the EP4 receptor and is useful for research in the DSS-induced colitis mouse model.</p>

DSP-1053: Benzylpiperidine-based, potent SERT inhibitor (Ki=1.02nM), partial 5-HT1A receptor agonist (Ki=5.05nM), antidepressant.

R-137696 is an orally active 5-HT1A receptor agonist that facilitates the relaxation of the proximal stomach. It is utilized in research related to functional dyspepsia.

Flucopride (Compound 4a) acts as an acetylcholinesterase inhibitor (AChE) with an IC50 value of 24 nM and serves as a partial agonist for the human 5-HT4 receptor (5-HT4R) with a Ki of 9.6 nM for (h)5-HT4R. It promotes non-amyloidogenic processing of APP in COS-7 cells transiently expressing (h)5-HT4R with an EC50 of 23.0 nM. Flucopride is also likely to exhibit significant gastrointestinal tract (GIT) penetration and blood-brain barrier (BBB) permeability, as determined in PAMPA experiments.

Butopamine hydrochloride is an orally active inotropic compound that is more effective at increasing heart rate compared to Dobutamine.

AB-FUBINACA 3-fluorobenzyl isomer is a synthetic cannabinoid and an indazole derivative, exhibiting high affinity for central CB1 receptors (Ki= 0.9 nM) and possessing anticonvulsant activity.

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

(±)-Penbutolol ((Rac)-Penbutolol) is the racemic form of Penbutolol. It acts as an orally active β-adrenergic receptor antagonist. (±)-Penbutolol mitigates the tachycardia induced by exercise, reduces the increase in peak expiratory flow rate (PEFR) caused by physical activity, and decreases plasma renin activity (PRA) at rest. The peak plasma concentration of this compound is achieved one hour after oral administration, with a half-life of 4.5 hours, and it is metabolized into active metabolites in the body. This compound is utilized in research related to cardiovascular diseases.

Tipindole is a serotonin antagonist utilized in research related to depression.

Sulfinalol hydrochloride is an orally active β-adrenoceptor (β-adrenoceptor) antagonist that exhibits direct vasodilatory activity. It is also classified as an antihypertensive agent.

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).

Ac-Atovaquone, an ester-acetylated derivative of atovaquone, acts as a potent inhibitor of cytochrome bc1 (cytochrome bc1). This compound shows potential for use in malaria research.

<p>GHSR-1a agonist-1 (Compound 4b) is an orally active agonist of the human growth hormone secretagogue receptor 1a (GHSR-1a) with an EC50 of 0.49 nM. It effectively stimulates the release of endogenous growth hormone by activating GHSR-1a. Doses as low as 0.1 mg/kg (administered orally) can increase body weight and length in 4-week-old rats. GHSR-1a agonist-1 is applicable in research on pediatric growth and developmental delays.</p>

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

CP-865569 is a CCR1 antagonist useful in the research of inflammatory and autoimmune diseases, including conditions such as rheumatoid arthritis and multiple sclerosis.

A1 adenosine receptor antagonist

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

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

<p>AChE/BChE-IN-21 is an antagonist of the histamine H3 receptor, a calcium channel blocker, and an acetylcholinesterase inhibitor. It exhibits neuroprotective activities against H2O2 and Aβ1-40, and can restore cognitive functions in AD mice.</p>

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

5-HT7R antagonist 1 is a G protein-biased antagonist with Ki of 6.5 nM for 5-HT 7R.

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.

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].

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.

Pareptide monohydrochloride is a metabolically stable analog of melatonin inhibitor (MIF).

<p>BD-1047 is a selective functional antagonist of sigma receptors. It can alleviate climbing behavior induced by Apomorphine and head twitching caused by Phencyclidine.</p>

Atumelnant (CRN04894) is an MC2R antagonist used in the study of congenital adrenocortical hyperplasia (CAH) and Cushing's disease (CD).

MRS2179 blocks turkey P2Y1 receptor (Kb 102 nM, pA2 6.99), affects platelet aggregation, and has varying IC50s on P2 receptors.

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

MF-592: EP4 receptor antagonist, hEP4 IC50 3 nM, hWB IC50 78 nM, great oral PK, rat arthritis ED50 0.1 mg/kg/day, promising for development.

<p>Fasitibant is a potent and selective nonpeptide kinin B2 receptor antagonist.</p>

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.

JKC 302 is an ET-A receptor antagonist that partially inhibits the contraction of tracheal rings in asthmatic rats induced by ET-1.

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

Inupadenant (EOS-850) is a selective A2a receptor antagonist, targeting immunosuppression in tumors.

Teoprolol is a blocker of β-adrenergic receptor.

Monlunabant ((S)-MRI-1891), a solid dispersion compound, functions as an inhibitor of the cannabinoid CB1 receptor [1].

YM158 free base is a potent and selective antagonist of TXA2 and LTD4 receptor (pA2s: about 8.81 and 8.87).

Selective, orally active PAR-1 antagonist with an IC50 of 7 nM, potential for cardiovascular disease studies.

LY 245769 is an inhibitor of leukotriene E4 (LTE4).

Merigolix is a potent gonadotrophin releasing hormone (GnRH) antagonist .

<p>(S)-YNT-3708 is the S-isomer of YNT-3708, demonstrating relatively low activity against OX1R and OX2R receptors, with EC50 values of 3595 nM and 1661 nM, respectively.</p>

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.

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

PF-07054894: potent CCR6 antagonist, targets GPCR, for inflammatory bowel disease research.

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

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

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).

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.

<p>GnRH antagonist 2 is a GnRH receptor antagonist, useful for studying endocrine diseases.</p>

Aplaviroc (AK 602), a SDP derivative, is a CCR5 antagonist. With IC50s of 0.1-0.4 nM for HIV-1Ba-L, HIV-1JRFL and HIV-1MOKW.

<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>

SR 140333 is a NK1 receptor antagonist.

Diosuxentan is an inhibitor of ETA and is utilized in research pertaining to cardiovascular, renal, and neuronal inflammatory diseases.

<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>

<p>BNS808 is an orally active, selective CB1R antagonist with an IC50 of 0.8 nM, demonstrating significant selectivity for CB2R and minimal brain penetration. It is being studied for the treatment of obesity and related metabolic complications, such as metabolic dysfunction-associated steatotic liver disease (MASLD). BNS808 reduces drug exposure to the central nervous system, enhancing safety, and minimizes drug interactions through high plasma protein binding.</p>

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

Sitamaquine hydrochloride (WR 6026) is an orally active 8-aminoquinoline analog with antileishmanial activity. This compound inhibits mitochondrial complex II (succinate dehydrogenase) and is characterized by its lipophilic weak base properties. It rapidly accumulates in the acidic compartments of Leishmania parasites, predominantly localizing within the acidocalcisomes.

(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

5-HT2 receptor antagonist

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].

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].

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

<p>BI 703704, a soluble guanylate cyclase (sGC) activator, inhibits the progression of diabetic nephropathy in the ZSF1 rat [1].</p>

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

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

<p>CS-0777 is a potent, selective, and orally active S1P1 agonist (sphingosine 1-phosphate receptor modulator).</p>

BAY-899, oral LH-R antagonist, IC50: 185 nM (hLH), 46 nM (rLH), lowers sex hormones in vivo.

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

Elsovaptan is an antagonist of the vasopressin receptor and is applicable for research in Alzheimer's disease.

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

BI-685509: potent, oral sGC activator, boosts cGMP, enhances NO pathways, for CKD/DKD research.

(E/Z)-Ozagrel (sodium) [(E/Z)-OKY-046 (sodium)] is a mixture of the EZ isomers of Ozagrel (sodium). It acts as a thromboxane A2 (TXA2) synthase inhibitor. As an antiplatelet agent, Ozagrel (sodium) selectively inhibits human platelet aggregation, with an IC50 of 53.12 μM.

S1PR1 agonist 2 is potent for autoimmune research (from WO2021175225A1).