GPCR/G-Protein

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

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.

Cendifensine functions as a monoamine reuptake inhibitor, targeting the serotonin transporter (SERT), norepinephrine transporter (NET), and dopamine transporter (DAT).

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

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.

Serlopitant is a selective antagonist of Neurokinin-1 (NK-1) receptor.

L-97-1 is an antagonist of the adenosine A1 receptor.

LK-732 is a thrombin inhibitor with antithrombotic activity. It exhibits dose-dependent inhibition in models of hypercoagulability, with an IC50 value of 1.3 mg/kg. LK-732 is used in cardiovascular and cerebrovascular research.

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

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.

AChE-IN-5: oral, crosses blood-brain barrier, targets AChE/5-HT1A/SERT, potent with 2.29 nM IC50.

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.

SAR-150640, a selective β3-adrenergic receptor agonist, prevents an increase in MMP activity and production observed after LPS stimulation or in cases of chorioamnionitis.

Potent, selective D4R antagonist; IC50 = 6.87 µM; potential in Parkinson’s disease research.

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

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.

inhibitor of human CCR5 binding to HIV-1 gp120

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

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

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

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.

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.

<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>

M1069 is an oral A2A/A2B receptor antagonist, 100x more selective over A1/A3, with antitumor properties by blocking adenosine's immunosuppressive effects.

U91356 is an agonist of the dopamine receptors.

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.

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.

Avitriptan is a 5-HT1B/1D receptor agonist with pKi values of 7.44 for 5-HT1Brat, 7.68 for 5-HT1Bhuman, and 8.36 for 5-HT1Dhuman. It can induce contraction in isolated coronary arteries and is used for the treatment of migraines.

Selective, high affinity competitive antagonist of the P2Y1 receptor

(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.

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.

COX-2-IN-6: Potent, selective COX-2 inhibitor; oral; IC50 0.84μM, Ki 69nM; blocks PGE2 synthesis; prevents colorectal cancer.

WIN 66306: Cyclic heptapeptide, blocks NK1/NK2 receptors, inhibits substance P-triggered contractions in guinea pig ileum.

LAB687 (Compound 2a) is an inhibitor of microsomal triglyceride transfer protein (MTP) with an IC50 of 0.9 nM for inhibiting the secretion of apolipoprotein B (apoB) in HepG2 cells. Additionally, LAB687 acts as a Smoothened (Smo) antagonist, exhibiting IC50 values of 2.48 μM and 3.42 μM for mouse and human Smo receptors, respectively. This compound is effective in reducing triglyceride and low-density lipoprotein cholesterol (LDL-C) levels and in inhibiting the Hedgehog signaling pathway.

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

YM-31636 (free base) is an orally active, potent, and selective agonist of the 5-HT3 receptor with a pKi value of 9.67. This compound induces contraction in isolated guinea pig distal colon and provokes tachycardia in isolated guinea pig right atrium, demonstrating a relative intrinsic activity of about 0.23. YM-31636 (free base) holds potential for research in constipation management.

Compound 6.4, also known as 5-HT7R antagonist 3, is a selective antagonist of the 5-HT7R with a Ki of 8 nM. It exhibits significantly less affinity towards D2R, 5-HT1AR, and 5-HT2AR with Ki values of 511 nM, 8930 nM, and 5786 nM, respectively. In mice, 5-HT7R antagonist 3 demonstrates anti-depressant and anti-anxiety activities.

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

Nocloprost (SH 475) is a prostaglandin E2 (PGE2) analog, an EP1 and EP3 receptor agonist with local gastric protection and ulcer healing effects.

BMS-986104 is an effective selective modulator of the S1P1 receptor. It demonstrates efficacy in the mouse EAE model, comparable to that of FTY720. Furthermore, BMS-986104 shows promising remyelination properties in three-dimensional brain cell cultures subjected to lysophosphatidylcholine (LPC)-induced demyelination.

LAS195319 is a potent and selective inhaled PI3Kδ Inhibitor (IC50 = 0.5 nM) for the Treatment of Respiratory Diseases.

Fosrolapitant is an antagonist of the neurokinin 1 (NK1) receptor.

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.

Rimegepant (BMS-927711/BHV-3000): oral CGRP blocker for migraines, effective without vasoconstriction, beats placebo, well-tolerated.

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].

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

Quinagolide Free Base is a non-ergot dopamine D(2)-agonist.

O-1269 acts as a partial agonist for the cannabinoid receptor 1 (CB1R), with a binding affinity (Ki) of 32 nM. Additionally, it exhibits analgesic properties.

Compound 20A, known as GLP-1 receptor agonist 12, acts as an agonist of the GLP receptor. It is utilized in researching diseases like diabetes [1].

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

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].

H-Glu-Thr-OH (L-α-Glutamyl-L-threonine) is a dipeptide composed of two amino acids—glutamic acid (Glu) and threonine (Thr)—linked by a peptide bond and functions as an agonist of the extracellular calcium-sensing receptor (CaSR).

GLP-1 receptor agonist 15 (Example 4) is a GLP receptor agonist with an EC50 of 0.74 nM. It exhibits an IC50 of 10.1 μM against the hERG potassium ion channel. This compound is applicable for research in the diabetes field.

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.

Vibegron (MK-4618) is an effective and selective Beta 3 adrenergic receptor agonist, used to treat overactive bladder (OAB).

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.

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

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

CBR Agonist-2: CB1 receptor agonist, EC50 - 960 nM, Ki - 970 nM, useful for hCB1R-related disease research.

RU 52583 is an alpha 2-adrenergic receptor antagonist.

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

12(S)-HEPE, made from EPA by 12-LO, is an anti-inflammatory ω-3 derivative affecting leukotriene formation.

<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>

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

Dopamine D3 receptor antagonist-1 is a dopamine D3 receptor selective or multi-targeting ligand with a Ki value of 1.58 nM that has demonstrated therapeutic

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].

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

<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>

Compound 23: H3R antagonist with 170 nM Ki; inhibits AChE, BChE, hMAO B; IC50s: 180, 880, 775 nM; anti-pain, memory boost; crosses BBB. [1]

Thielavin B, from Thielavia terricola, inhibits prostaglandin E2 synthesis and reduces rat oedema.

GLP-1 receptoragonist 16 (Example 53) is a GLP-1 agonist applicable for research in diabetes, obesity, or diseases related to non-alcoholic steatohepatitis.

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

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.

LTD4 antagonist 1 is a potent and orally active antagonist of leukotriene D4 (LTD4; Ki: 0.57 nM).

<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>

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.

CGRP antagonist 7 is a potent calcitonin gene-related peptide receptor (CGRP) antagonist with a Ki value of 0.029 nM. It effectively inhibits CGRP receptor-mediated cyclic adenosine monophosphate (cAMP) production, with an IC50 value of 1.5 nM. This compound is useful in migraine research.

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].

Beloxepin is an oral dual selective inhibitor of serotonin and norepinephrine uptake.

(+)-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.

Delmadinone acetate is an orally active compound used to control estrus and ovulation in both female and male pets. It induces adrenal suppression by inhibiting the pituitary release of ACTH.

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].

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.

CI-936 (MRS-3310) is an orally active A2 agonist with a binding affinity of 25 nM. In preclinical studies, it has demonstrated potent and selective effects, indicating potential antipsychotic efficacy. Additionally, CI-936 inhibits exploratory behavior in mice.

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

Remlifanserin is a potent inverse agonist of the serotonin receptor (5-HT2A).

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

SB 258741 hydrochloride is a potent antagonist of the 5-HT 7 receptor, designed specifically for studying schizophrenia [1].

KF26777 is a potent and selective antagonist of adenosine A3 receptor.

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.

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.

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.

Edonentan (BMS 207940) hydrate effectively blocks the endothelin A (ETA) receptor as a potent and selective antagonist, featuring a K i of 10 pM. It exhibits complete (100%) oral bioavailability in rats [1].

<p>S1PR1 agonist 1 is a potent agonist of S1PR1. S1PR1 agonist 1 has potential in autoimmune diseases.</p>

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].

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

MCTR1, a pro-resolving mediator derived from DHA, promotes tissue repair and reduces inflammation by enhancing phagocytosis and decreasing eicosanoids.

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

(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