G Protein Coupled Receptors (GPCRs) perceive many extracellular signals and transduce them to heterotrimeric G proteins, which further transduce these signals intracellular to appropriate downstream effectors and thereby play an important role in various signaling pathways. G proteins are specialized proteins with the ability to bind the nucleotides guanosine triphosphate (GTP) and guanosine diphosphate (GDP). In unstimulated cells, the state of G alpha is defined by its interaction with GDP, G beta-gamma, and a GPCR. Upon receptor stimulation by a ligand, G alpha dissociates from the receptor and G beta-gamma, and GTP is exchanged for the bound GDP, which leads to G alpha activation. G alpha then goes on to activate other molecules in the cell. These effects include activating the MAPK and PI3K pathways, as well as inhibition of the Na+/H+ exchanger in the plasma membrane, and the lowering of intracellular Ca2+ levels.

Most human GPCRs can be grouped into five main families named; Glutamate, Rhodopsin, Adhesion, Frizzled/Taste2, and Secretin, forming the GRAFS classification system.

A series of studies showed that aberrant GPCR Signaling including those for GPCR-PCa, PSGR2, CaSR, GPR30, and GPR39 are associated with tumorigenesis or metastasis, thus interfering with these receptors and their downstream targets might provide an opportunity for the development of new strategies for cancer diagnosis, prevention and treatment. At present, modulators of GPCRs form a key area for the pharmaceutical industry, representing approximately 27% of all FDA-approved drugs.

References:
[1] Moreira IS. Biochim Biophys Acta. 2014 Jan;1840(1):16-33.
[2] Tuteja N. Plant Signal Behav. 2009 Oct;4(10):942-7.
[3] Williams C, et al. Methods Mol Biol. 2009;552:39-50.
[4] Schiöth HB, et al. Gen Comp Endocrinol. 2005 May 15;142(1-2):94-101.
[5] Wu J, et al. Cancer Genomics Proteomics. 2012 Jan;9(1):37-50.


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Bromerguride

Bromerguride (2-Bromolisuride) is an analogue of the ergot dopamine agonist Lisuride (HY-12713). Bromerguride exhibits central antidopaminergic properties[1].

  • CAS Number: 83455-48-5
  • MF: C20H25BrN4O
  • MW: 417.34300
  • Catalog: Dopamine Receptor
  • Density: 1.45g/cm3
  • Boiling Point: 641.4ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 341.7ºC

BI-9667

CCR1 antagonist 8 (compound 19n), a third azaindazole series compound, is a CCR1 antagonist clinical candidate, with an IC50 of 1.8 nM in Ca2+ flux assay[1].

  • CAS Number: 1295298-26-8
  • MF: C22H18FN5O3S
  • MW: 451.47
  • Catalog: CCR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SLIGRL-NH2 2TFA

Protease-Activated Receptor-2 Activating Peptide is an agonist of Protease-Activated Receptor-2 (PAR-2).

  • CAS Number: 171436-38-7
  • MF: C29H56N10O7
  • MW: 656.81800
  • Catalog: Peptides
  • Density: 1.342g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(rac)-Nebivolol-d8

(Rac)-Nebivolol-d8 ((rac)-R 065824-d8) is a labelled racemic Nebivolol. Nebivolol selectively inhibits β1- adrenergic receptor with IC50 of 0.8 nM[1][2].

  • CAS Number: 1219166-00-3
  • MF: C22H17D8F2NO4
  • MW: 413.48400
  • Catalog: Adrenergic Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

J-2156

J-2156 is a high potent, selective somatostatin receptor type 4 (SST4 receptor) agonist with IC50s of 0.05 nM and 0.07 nM for human and rat SST4 receptors, respectively. The ED50 of J-2156 in rats for the relief of mechanical allodynia and mechanical hyperalgesia in the ipsilateral hindpaws was 3.7 and 8.0 mg/kg, respectively[1].

  • CAS Number: 848647-56-3
  • MF: C24H28N4O4S
  • MW: 468.57
  • Catalog: Somatostatin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Raclopride

Raclopride is a dopamine D2/D3 receptor antagonist, which binds to D2 and D3 receptors with dissociation constants (Kis) of 1.8 nM and 3.5 nM, respectively, but has a very low affinity for D1 and D4 receptors with Kis of 18000 nM and 2400 nM, respectively[1].

  • CAS Number: 84225-95-6
  • MF: C15H20Cl2N2O3
  • MW: 347.24
  • Catalog: Dopamine Receptor
  • Density: 1.288g/cm3
  • Boiling Point: 420.3ºC at 760 mmHg
  • Melting Point: 54 °C
  • Flash Point: 208ºC

Nuciferine

Nuciferine is an antagonist at 5-HT2A (IC50=478 nM), 5-HT2C (IC50=131 nM), and 5-HT2B (IC50=1 μM), an inverse agonist at 5-HT7 (IC50=150 nM), a partial agonist at D2 (EC50=64 nM), D5 (EC50=2.6 μM) and 5-HT6 (EC50=700 nM), an agonist at 5-HT1A (EC50=3.2 μM) and D4 (EC50=2 μM) receptor.

  • CAS Number: 475-83-2
  • MF: C19H21NO2
  • MW: 295.375
  • Catalog: 5-HT Receptor
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 430.7±45.0 °C at 760 mmHg
  • Melting Point: 165.5°C
  • Flash Point: 151.9±17.3 °C

Kuwanon H

Kuwanon H is a flavonoid isolated from Morus bombycis, which acts as a potent non-peptide bombesin receptor antagonist. Kuwanon H selectively inhibits binding of gastrin releasing peptide CRP to GRP-preferring recepotr, with a Ki value of 290 nM in cells[1].

  • CAS Number: 76472-87-2
  • MF: C45H44O11
  • MW: 760.82400
  • Catalog: Bombesin Receptor
  • Density: 1.371g/cm3
  • Boiling Point: 969.8ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 292.5ºC

UP202-56

UP202-56 is an adenosine analogue, which is an adenosinergic agonist.

  • CAS Number: 163838-04-8
  • MF: C34H38N6O4
  • MW: 594.7
  • Catalog: Adenosine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SSR 149415

Nelivaptan (SSR-149415) is a selective and orally active vasopressin V1b Receptor antagonist (Ki: 3.7 and 1.3 nM for native and recombinant rat V1b receptors, respectively). Nelivaptan inhibits arginine vasopressin (AVP)-induced Ca2+ increase and corticotropin secretion. Nelivaptan can be used for research of stress and anxiety[1].

  • CAS Number: 439687-69-1
  • MF: C30H32ClN3O8S
  • MW: 630.11
  • Catalog: Vasopressin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(D-Phe7)-α-MSH

(D-Phe7)-α-MSH is an α-MSH analogue[1].

  • CAS Number: 92937-43-4
  • MF: C77H109N21O19S
  • MW: 1664.88
  • Catalog: Cancer
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Dimaprit dihydrochloride

Dimaprit dihydrochloride is a selective histamine H2 receptor agonist, it also inhibits nNOS with an IC50 of 49 μM. Dimaprit dihydrochloride can stimulate gastric acid secretion[1][2].

  • CAS Number: 23256-33-9
  • MF: C6H17Cl2N3S
  • MW: 234.19000
  • Catalog: Histamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CX-5011

CX-5011 is a CK2 inhibitor. CX-5011 also induces Rac1 activation. CX-5011 induces apoptosis and induces cancer cell death[1][2].

  • CAS Number: 1333382-30-1
  • MF: C20H11N4NaO2
  • MW: 362.31700
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

VU 0360172 hydrochloride

VU0360172 hydrochloride is a potent and selective mGlu5 receptor positive allosteric modulator (PAM) with an EC50 value of 16 nM and a Ki of 195 nM, respectively. VU0360172 hydrochloride stimulates polyphosphoinositide (PI) hydrolysis in vivo, which is abrogated in mGlu5 receptors gene deleted mice[1].

  • CAS Number: 1309976-62-2
  • MF: C18H16ClFN2O
  • MW: 330.78
  • Catalog: mGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Doxylaminephenyl-d5

Doxylamine D5 is deuterium labeled Doxylamine.

  • CAS Number: 1173020-59-1
  • MF: C17H17D5N2O
  • MW: 275.40000
  • Catalog: Histamine Receptor
  • Density: N/A
  • Boiling Point: 137-141 °C(lit.)
  • Melting Point: N/A
  • Flash Point: 2 °C

(±)-ERIODICTYOL

(±)-Eriodictyol ((±)-Huazhongilexone), a flavonoid, is a potent melanogenesis inhibitor with an IC50 of 48 μM. (±)-Eriodictyol suppresses tyrosinase, TRP-1, and TRP-2 mRNA expression. (±)-Eriodictyol has strong anti-plasmin activities[1].

  • CAS Number: 4049-38-1
  • MF: C15H12O6
  • MW: 288.25200
  • Catalog: Metabolic Disease
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

KRAS G12C inhibitor 21

KRAS G12C inhibitor 21 is a KRAS G12C inhibitor extracted from patent WO2021219090A1, example 7[1].

  • CAS Number: 2737269-61-1
  • MF: C34H30ClN3O4
  • MW: 580.07
  • Catalog: Ras
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(±)-LY 395756

(±)-LY395756 is an agonist of mGlu2 receptor and an antagonist of mGlu3 receptor. (±)-LY395756 can distinguish the native mGlu2 and mGlu3 receptors[1].

  • CAS Number: 852679-66-4
  • MF: C9H13NO4
  • MW: 199.20
  • Catalog: mGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

R243

R243 is a potent, small molecule CCR8 antagonist that inhibits CCR8 signaling and chemotaxis, inhibits CCL1-induced Ca2+ flux and CCL1-driven peritoneal macrophages aggregation at 0.2 uM; attenuated secretion of TNF-α, IL-6, and most strikingly IL-10 from WT PMφ (peritoneal macrophages), but not BMMφ (bone marrow-derived macrophages); shows suppressed c-JNK activity and NF-κB signaling after LPS treatment, suppresses LPS-induced cytokine secretion; attenuates peritoneal adhesions in vivo in CCR8-/- mice, also prevents hapten-induced colitis.

  • CAS Number: 688352-84-3
  • MF: C21H27NO4
  • MW: 357.45
  • Catalog: CCR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

antarelix

Teverelix (EP 24332) is a GnRH antagonist. Teverelix binds competitively and reversibly to GnRH receptors, thereby suppressing the release of LH and FSH. Teverelix can be used in the research of prostatic hyperplasia, endometriosis, and prostate cancer[1][2].

  • CAS Number: 151272-78-5
  • MF: C74H100ClN15O14
  • MW: 1459.131
  • Catalog: GNRH Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 1692.9±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 977.6±34.3 °C

Alosetron hydrochloride

Alosetron Hcl is a Serotonin 5HT3-receptor antagonist that is used in treatment of irritable bowel syndrome.IC50 Value: Target: 5-HT ReceptorAlosetron has an antagonist action on the 5-HT3 receptors of the enteric nervous system of the gastrointestinal tract. While being a 5-HT3 antagonist like ondansetron, it is not classified or approved as an antiemetic. Since stimulation of 5-HT3 receptors is positively correlated with gastrointestinal motility, alosetron's 5-HT3 antagonism slows the movement of fecal matter through the large intestine, increasing the extent to which water is absorbed, and decreasing the moisture and volume of the remaining waste products. From Wikipedia.

  • CAS Number: 122852-69-1
  • MF: C17H19ClN4O
  • MW: 330.812
  • Catalog: 5-HT Receptor
  • Density: 1.34g/cm3
  • Boiling Point: 648.1ºC at 760 mmHg
  • Melting Point: 288-291ºC
  • Flash Point: 345.8ºC

R 715

R715 is a selective bradykinin B1 receptor antagonist. R715 significantly attenuates the hyperalgesic effect developed in Streptozotocin(HY-13753)-diabetic mice[1].

  • CAS Number: 185052-09-9
  • MF: C57H81N13O12
  • MW: 1140.33000
  • Catalog: Bradykinin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Sinomenine HCl

Sinomenine hydrochloride is a blocker of the NF-κB activation and also an activator of μ-opioid receptor.

  • CAS Number: 6080-33-7
  • MF: C19H24ClNO4
  • MW: 365.851
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: 513.6ºC at 760 mmHg
  • Melting Point: 231.0 to 235.0 °C
  • Flash Point: 264.4ºC

Iloperidone (hydrochloride)

Iloperidone (hydrochloride) is a D(2)/5-HT(2) receptor antagonistis, which is an atypical antipsychotic for the treatment of schizophrenia symptoms.Target: 5-HT receptor; Dopamine receptorIloperidone (hydrochloride) is the hydrochloride of iloperidone, iloperidone (HP 873; 1-[4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy] -3- methoxyphenyl]ethanone) is a compound currently in clinical trials for the treatment of schizophrenia. Iloperidone displays affinity for dopamine D2 receptors and for 5-HT2A receptors and has a variety of in vivo activities suggestive of an atypical antipsychotic. Iloperidone displayed higher affinity for the dopamine D3 receptor (Ki = 7.1 nM) than for the dopamine D4 receptor (Ki = 25 nM). Iloperidone displayed high affinity for the 5-HT6 and 5-HT7 receptors (Ki = 42.7 and 21.6 nM, respectively), and was found to have higher affinity for the 5-HT2A (Ki = 5.6 nM) than for the 5-HT2C receptor (Ki = 42.8 nM) [1]. Iloperidone was eliminated slowly, with a mean t1/2 of 13.5 to 14.0 hours. Coadministration with food did not significantly affect AUC, tmax, or Cmax. These results indicate that the rate of iloperidone's absorption is decreased, but the overall bioavailability is unchanged, when the drug is taken with food. Orthostatic hypotension, dizziness, and somnolence were the most commonly reported adverse events [2]. Iloperidone pharmacokinetics and pharmacodynamics are presented herein, together with an evaluation of clinical safety and efficacy results [3].Clinical indications: Post traumatic stress disorder; Schizophrenia Toxicity: Commonly observed adverse reactions (incidence ≥5% and two-fold greater than placebo) were: dizziness, dry mouth, fatigue, nasal congestion, orthostatic hypotension, somnolence, tachycardia, and weight increased.

  • CAS Number: 1299470-39-5
  • MF: C24H28ClFN2O4
  • MW: 462.94200
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ML 141

ML141(CID-2950007) is a potent, selective and reversible non-competitive inhibitor of Cdc42 GTPase(IC50=200 nM) with low micromolar potency and selectivity against other members of the Rho family of GTPases (Rac1, Rab2, Rab7). IC50 value: 200 nM [1]Target: Cdc42 inhibitorin vitro: In the primary HTS bead-based assay using 1 mM EDTA and 100 nM BODIPY-FL-GTP, potency for CID2950007 was IC50 = 2.6 and 5.4 μM for Cdc42 wild type and activated mutant, respectively [1]. ML141 exposure also enhanced the ability of TMX to suppress BLBC cell growth, through both induction of cell death and suppression of cell division [2]. in vivo: Treatment with ML141 + TMX caused a suppression of further tumour growth in vivo [2]. Parallel suppression of the conserved brain CDC42 activity by intracerebroventricular ML141 injection caused acute anxiety in mice [3]. using a pilocarpine-induced epileptic model, we found that pretreatment with ML141, a specific inhibitor of Cdc42, reduces seizure severity [4].

  • CAS Number: 71203-35-5
  • MF: C22H21N3O3S
  • MW: 407.485
  • Catalog: Ras
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 622.9±65.0 °C at 760 mmHg
  • Melting Point: 216 °C
  • Flash Point: 330.5±34.3 °C

LY255283

LY255283 is a LTB4 receptor (BLT2) antagonist, with an IC50 of ~100 nM for [3H]LTB4 binding to guinea pig lung membranes[1][2][3][4].

  • CAS Number: 117690-79-6
  • MF: C19H28N4O3
  • MW: 360.451
  • Catalog: Leukotriene Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 573.4±60.0 °C at 760 mmHg
  • Melting Point: 160-162 °C
  • Flash Point: 300.6±32.9 °C

KRAS G12C inhibitor 41

KRAS G12C inhibitor 41 is a potent inhibitor of KRAS G12C. The Ras family of proteins is an important intracellular signaling molecule that plays an important role in growth and development. KRAS G12C inhibitor 41 has the potential for the research of KRAS G12C-mediated cancer (extracted from patent WO2021129824A1, compound 121)[1].

  • CAS Number: 2660014-65-1
  • MF: C36H37ClFN9O2
  • MW: 682.19
  • Catalog: Ras
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Irindalone

Irindalone is a novel serotonin 5-HT2 antagonist.

  • CAS Number: 96478-43-2
  • MF: C24H29FN4O
  • MW: 408.51200
  • Catalog: 5-HT Receptor
  • Density: 1.219g/cm3
  • Boiling Point: 605.7ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 320.1ºC

Loperamide hydrochloride

Loperamide hydrochloride is an opiate receptor agonist for the treatment of diarrhea.

  • CAS Number: 34552-83-5
  • MF: C29H34Cl2N2O2
  • MW: 513.498
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: 647.2ºC at 760 mmHg
  • Melting Point: 223-225°C
  • Flash Point: 345.2ºC

2H-Benzimidazol-2-one,1,3-dihydro-1-[1-(2-phenoxyethyl)-4-piperidinyl]-

Oxiperomide is an orally active dopamine-blocking agent[1].

  • CAS Number: 5322-53-2
  • MF: C20H23N3O2
  • MW: 337.41600
  • Catalog: Dopamine Receptor
  • Density: 1.208g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A