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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LP-471756

LP-471756 is a potent GPR139 antagonist with an IC50 value of 640 nM. LP-471756 inhibits LP-360924-stimulated cAMP production[1][2].

  • CAS Number: 413605-11-5
  • MF: C19H23NO2S
  • MW: 329.46
  • Catalog: GPR139
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Trimethobenzamide

Trimethobenzamide (Ro 2-9578 free base) is a blocker of the D2 receptor. Trimethobenzamide is an antiemetic used to prevent nausea and vomiting[1].

  • CAS Number: 138-56-7
  • MF: C21H28N2O5
  • MW: 388.45700
  • Catalog: Dopamine Receptor
  • Density: 1.131 g/cm3
  • Boiling Point: 506.9ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 260.4ºC

ARC-239

ARC 239 is an α2B/C-adrenergic receptor antagonist with pKi of 7.06 and 6.95 for rat kidney α2B and human α2C, respectively. ARC 239 also inhibits 5-HT1A receptor with a Ki of 63.1 nM[1][2].

  • CAS Number: 67339-62-2
  • MF: C24H29N3O3
  • MW: 407.51
  • Catalog: 5-HT Receptor
  • Density: 1.167g/cm3
  • Boiling Point: 595.8ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 314.1ºC

5-Carboxamidotryptamine maleate

5-Carboxamidotryptamine maleate (5-CT maleate) is a potent 5-HT1A, 5-HT1B, 5-HT1D, 5-HT5 and 5-HT7 receptors agonist[1][2][3].

  • CAS Number: 74885-72-6
  • MF: C15H17N3O5
  • MW: 319.31
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BW 246C

(8-epi)-BW 245C is the C-8 diastereomer of BW 245C (HY-101987). BW 245 C is a high affinity and selective PGD2 receptor agonist[1].

  • CAS Number: 65705-83-1
  • MF: C19H32N2O5
  • MW: 368.47
  • Catalog: Prostaglandin Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BP 897

BP 897 is a potent and partial dopamine D3 receptor agonist and a weak D2 receptor antagonist. BP 897 displays a high affinity at the dopamine D3 receptor (Ki=0.92 nM) and a 70 times lower affinity at the D2 receptor (Ki=61 nM). BP 897 exhibits selective inhibition of cocaine-seeking behavior[1].

  • CAS Number: 192384-87-5
  • MF: C26H31N3O2
  • MW: 417.54
  • Catalog: Dopamine Receptor
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 654.5±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 349.6±31.5 °C

Bivamelagon

MC-4R Agonist 2 (Example 1) is a MC4R agonist. MC-4R Agonist 2 can be used in the study of obesity, diabetes, inflammation, and erectile dysfunction[1].

  • CAS Number: 2641595-54-0
  • MF: C35H53ClN4O4
  • MW: 629.27
  • Catalog: Inflammation/Immunology
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PAR-4 Agonist Peptide, amide TFA

PAR-4 Agonist Peptide, amide TFA (PAR-4-AP TFA; AY-NH2 TFA) is a proteinase-activated receptor-4 (PAR-4) agonist, which has no effect on either PAR-1 or PAR-2 and whose effects are blocked by a PAR-4 antagonist[1].

  • CAS Number: 1228078-65-6
  • MF: C36H49F3N8O9
  • MW: 794.82
  • Catalog: Protease-Activated Receptor (PAR)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cinnarizine D8

Cinnarizine D8 is a deuterium labeled Cinnarizine. Cinnarizine is an antihistamine and a calcium channel blocker.

  • CAS Number: 1185242-27-6
  • MF: C26H20D8N2
  • MW: 376.56300
  • Catalog: Histamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

acebutolol

Acebutolol is an orally active β1 adrenergic receptor (β1AR) antagonist. Acebutolol is used for hypertension, angina pectoris and cardiac arrhythmias research[1][2][3].

  • CAS Number: 37517-30-9
  • MF: C18H28N2O4
  • MW: 336.426
  • Catalog: Adrenergic Receptor
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 564.1±50.0 °C at 760 mmHg
  • Melting Point: 119-123ºC
  • Flash Point: 295.0±30.1 °C

SOS1-IN-15

SOS1-IN-15 (Compound 37) is an orally active SOS1 inhibitor with an IC50 of 5 nM. SOS1-IN-15 is a promising drug candidate for the research of KRAS-driven cancer[1].

  • CAS Number: 2793404-47-2
  • MF: C28H27F3N6O2
  • MW: 536.55
  • Catalog: Ras
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CB2R/FAAH modulator-3

CB2R/FAAH modulator-3 (compound 27) is a dual targeting modulator that acts as a CB2R agonist and FAAH inhibitor. The Ki values for CB2R/FAAH modulator-3 are 20.1 and 67.6 nM for CB2R and CB1R, respectively, and the IC50 value for FAAH is 3.4 μM. CB2R/FAAH modulator-3 can be used in studies related to cancer, deleterious inflammatory cascades occurring in neurodegenerative diseases, and COVID-19 infection[1].

  • CAS Number: 2876918-67-9
  • MF: C22H31NO2
  • MW: 341.49
  • Catalog: Cannabinoid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

5-HT2 agonist-1

5-HT2 agonist-1 (Compound 24) is a 5-HT2A & 5-HT2B & 5-HT2C agonist, with IC50s of 10 nM, 8.3, and 1.6 nM respectively. 5-HT2 agonist-1 free base can be used for research of depression, alcoholism, tobacco and cocaine addiction, inflammation, cluster headache, PTSD, seizure disorders and other CNS disorders[1].

  • CAS Number: 2708279-78-9
  • MF: C19H23ClN2O2
  • MW: 346.85
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NBI 27914 hydrochloride

NBI-27914 (hydrochloride) is a selective Corticotropin-Releasing Factor 1 (CRF1) receptor antagonist with a Ki value of 1.7 nM[1][3][4].

  • CAS Number: 1215766-76-9
  • MF: C18H21Cl5N4
  • MW: 470.651
  • Catalog: CRFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

2-(E-2-decenoylamino)ethyl 2-(cyclohexylethyl) sulfide

2-(E-2-decenoylamino)ethyl 2-(cyclohexylethyl) sulfide is a compound that inhibits stress-induced ulcer and low toxicity, and can maintain the content of phospholipase A2 and prostaglandin E2 in ulcerated rats induced by water immersed restrained stress.

  • CAS Number: 137089-36-2
  • MF: C20H37NOS
  • MW: 339.57900
  • Catalog: Prostaglandin Receptor
  • Density: 0.954g/cm3
  • Boiling Point: 503.3ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 258.2ºC

Xylazine

Xylazine is α2 class of adrenergic receptor agonist.Target: Adrenergic ReceptorXylazine is a drug that is used for sedation, anesthesia, muscle relaxation, and analgesia in animals such as horses, cattle and other non-human mammals. An analogue of clonidine, it is an agonist at the α2 class of adrenergic receptor. Xylazine has recently emerged as a recreational drug, especially in Puerto Rico [1]. Administration of xylazine (0.17 mg/kg of body weight, diluted to a 10-ml volume, using 0.9% NaCl) induced approximately 2.5 hours of local analgesia without apparent side effects. Higher doses of xylazine caused mild hind limb ataxia. Administration of lidocaine induced a similar duration of analgesia, with severe hind limb ataxia (100% incidence). We concluded that xylazine given by epidural injection results in safe, effective perineal analgesia in horses [2].

  • CAS Number: 7361-61-7
  • MF: C12H16N2S
  • MW: 220.334
  • Catalog: Adrenergic Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 334.2±52.0 °C at 760 mmHg
  • Melting Point: 140ºC
  • Flash Point: 155.9±30.7 °C

Candesartan D4

Candesartan D4 is the deuterium labeled Candesartan, which is an angiotensin II receptor antagonist.

  • CAS Number: 1346604-70-3
  • MF: C24H16D4N6O3
  • MW: 444.47900
  • Catalog: Angiotensin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LRE1

LRE1 is a specific and allosteric inhibitor of soluble adenylyl cyclase.

  • CAS Number: 1252362-53-0
  • MF: C12H13ClN4S
  • MW: 280.78
  • Catalog: Adenylate Cyclase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TAK-875

Fasiglifam (TAK-875) is a potent, selective and orally bioavailable GPR40 agonist with EC50 of 72 nM.

  • CAS Number: 1000413-72-8
  • MF: C29H32O7S
  • MW: 524.625
  • Catalog: GPR40
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 739.1±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 400.8±32.9 °C

SV-156

Highly selective D2 dopamine receptor antagonist

  • CAS Number: 873445-60-4
  • MF: C21H23BrN2O2
  • MW: 415.32
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

S-777469

S-777469 is a selective and orally available cannabinoid type 2 receptor (CB2) agonist with a Ki of 36 nM. S-777469 significantly suppresses compound 48/80-induced scratching behavior in mice in a dose-dependent manner. S-777469 produces its antipruritic effects by inhibiting itch signal transmission through CB2 agonism[1][2].

  • CAS Number: 885496-53-7
  • MF: C23H27FN2O4
  • MW: 414.47
  • Catalog: Cannabinoid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Metixene hydrochloride

Metixene hydrochloride is an anticholinergic antiparkinsonian agent, potently inhibits binding of quinuclidinyl benzilate (QNB) to the muscarinic receptor in rat brain cortical tissue, with an IC50 of 55 nM and a Kd of 15 nM[1].

  • CAS Number: 1553-34-0
  • MF: C20H24ClNS
  • MW: 345.93
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: 419.7ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 207.6ºC

Ziprasidone

Ziprasidone(CP88059) is a combined 5-HT (serotonin) and dopamine receptor antagonist which exhibits potent effects of antipsychotic activity.IC50 value:Target: 5-HT receptor; Dopamine receptorZiprasidone possesses an in vitro 5-HT2A/dopamine D2 receptor affinity ratio higher than any clinically available antipsychotic agent. In vivo, ziprasidone antagonizes 5-HT2A receptor-induced head twitch with 6-fold higher potency than for blockade of d-amphetamine-induced hyperactivity, a measure of central dopamine D2 receptor antagonism. Ziprasidone also has high affinity for the 5-HT1A, 5-HT1D and 5-HT2C receptor subtypes, which may further enhance its therapeutic potential [1]. Ziprasidone sulfoxide and sulfone were the major metabolites in human serum. The affinities of the sulfoxide and sulfone metabolites for 5-HT2 and D2 receptors are low with respect to ziprasidone, and are thus unlikely to contribute to its antipsychotic effects [2]. Ziprasidone was associated with significant differential adverse effects relative to placebo in BPM, BPD, and schizophrenia with no significant difference in weight gain in all 3 groups. Self-reported somnolence was increased across the 3 conditions. Subjects with BPM were more vulnerable to EPS than those with BPD or schizophrenia [3].Clinical indications: Bipolar I disorder; Bipolar disorder; Mania; SchizophreniaFDA Approved Date: February 2001

  • CAS Number: 146939-27-7
  • MF: C21H21ClN4OS
  • MW: 412.94
  • Catalog: 5-HT Receptor
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 554.8±50.0 °C at 760 mmHg
  • Melting Point: 213-215°C
  • Flash Point: 289.3±30.1 °C

CYM 50308

CYM50308 is a potent, selective and high affinity sphingosine-1-phosphate receptor 4 (S1P4-R) agonist with an EC50 of 56 nM. CYM50308 displays 37-fold more selective for S1P4-R than S1P5-R. CYM50308 has no activity at S1P1-R, S1P2-R and S1P3-R subtypes at concentrations up to 25 μM[1].

  • CAS Number: 1345858-76-5
  • MF: C20H21F2N3O2S
  • MW: 405.461
  • Catalog: LPL Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 504.0±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 258.6±32.9 °C

Xenopus orexin A

Xenopus orexin A is a neuropeptides that identified as an endogenous ligands for an orphan G-protein-coupled receptor. Xenopus orexin A is a potent agonist of OX1R[1]

  • CAS Number: 254757-77-2
  • MF: C139H230N46O42S4
  • MW: 3345.86
  • Catalog: Orexin Receptor (OX Receptor)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

H-Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Val-Ile-His-OH

Angiotensinogen (1-13) (human) is a fragment of the renin substrate angiotensinogen. Angiotensinogen is naturally occurring substrate for renin and a precursor for all angiotensin peptides[1][2].

  • CAS Number: 82048-97-3
  • MF: C79H116N22O17
  • MW: 1645.903
  • Catalog: Angiotensin Receptor
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

VU 0365114

VU 0365114 is a mAChR M5 positive allosteric modulator, with an EC50 of 2.7 μM.

  • CAS Number: 1208222-39-2
  • MF: C22H14F3NO3
  • MW: 397.34700
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

L-771688

L-771688 is a highly selective α1A-Adrenoceptor antagonist with a Ki of 0.43±0.02 nM.

  • CAS Number: 200050-59-5
  • MF: C28H33F2N5O5
  • MW: 557.589
  • Catalog: Adrenergic Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PNU 142633

PNU-142633 is a high affinity, selective and orally active 5-HT1D receptor agonist with Kis of 6 nM and > 18 000 nM for human 5-HT1D receptor and human 5-HT1B receptor, respectively. PNU-142633 has anti-migraine efficacy[1][2].

  • CAS Number: 187665-65-2
  • MF: C24H30N4O3
  • MW: 422.52000
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(-)-Quinpirole hydrochloride

Quinpirole (Hydrochloride) is a high-affinity agonist dopamine D2/D3 receptor.

  • CAS Number: 85798-08-9
  • MF: C13H22ClN3
  • MW: 255.78700
  • Catalog: Dopamine Receptor
  • Density: 1.07g/cm3
  • Boiling Point: 383.9ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 186ºC