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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Org 27569

Org 27569 is a potent CB1 receptor allosteric modulator, which increases agonist binding, yet blocks agonist-induced CB1 signaling.

  • CAS Number: 868273-06-7
  • MF: C24H28ClN3O
  • MW: 409.952
  • Catalog: Cannabinoid Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 660.3±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 353.2±31.5 °C

Prazosin hydrochloride

Prazosin is an alpha-adrenergic blocker and is a sympatholytic drug used to treat high blood pressure and anxiety, PTSD, and panic disorder.Target: Adrenergic ReceptorPrazosin, is a sympatholytic drug used to treat high blood pressure and anxiety, PTSD, andpanic disorder. It is an alpha-adrenergic blocker that is specific for the alpha-1 receptors. These receptors are found on vascular smooth muscle, where they are responsible for the vasoconstrictive action of norepinephrine. They are also found throughout the central nervous system. As of 2013, prazosin is off-patent in the US, and the FDA has approved at least one generic manufacturer.In addition to its alpha-blocking activity, prazosin is an antagonist of the MT3 receptor (which is not present in humans), with selectivity for this receptor over the MT1 and MT2 receptors.Prazosin is orally active and has a minimal effect on cardiac function due to its alpha-1 receptor selectivity. However, when prazosin is initially started, heart rate and contractility go up in order to maintain the pre-treatment blood pressures because the body has reached homeostasis at its abnormally high blood pressure. The blood pressure lowering effect becomes apparent when prazosin is taken for longer periods of time. The heart rate and contractility go back down over time and blood pressure decreases.

  • CAS Number: 19237-84-4
  • MF: C19H22ClN5O4
  • MW: 419.862
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: 638.4ºC at 760 mmHg
  • Melting Point: 277 - 280 °C
  • Flash Point: 339.9ºC

NIBR0213

NIBR-0213 is a potent and selective S1P1 antagonist with efficacy in experimental autoimmune encephalomyelitis. NIBR-0213 displays potent and comparable potency on human and rat S1P1 (IC50 of 2.0 nM and 2.3 nM, respectively) in GTPγ35S assays[1].

  • CAS Number: 1233332-14-3
  • MF: C27H29ClN2O3
  • MW: 464.98
  • Catalog: LPL Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PF-07258669

PF-07258669 is a melanocortin-4 receptor (MC4) antagonist. PF-07258669 can be used for the research of cachexia, anorexia, or anorexia nervosa[1].

  • CAS Number: 2755890-53-8
  • MF: C25H27FN6O2
  • MW: 462.52
  • Catalog: Metabolic Disease
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Toreforant

Toreforant is a potent and selective histamine H4 receptor (H4R) antagonist, with a Ki at the human receptor of 8.4 nM.

  • CAS Number: 952494-46-1
  • MF: C23H32N6
  • MW: 392.540
  • Catalog: Histamine Receptor
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 611.2±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 323.4±34.3 °C

PSB11 hydrochloride

PSB11 hydrochloride is an antagonist with reverse excitatory activity for human A3 Adenosine Receptor with high affinity (Ki=2.3 nM)[1].

  • CAS Number: 453591-58-7
  • MF: C16H18ClN5O
  • MW: 331.800
  • Catalog: Adenosine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

4-hydroxy propranolol hcl

4-Hydroxypropranolol hydrochlorid is an active metabolite of Propranolol. 4-Hydroxypropranolol hydrochlorid is of comparable potency to Propranolol. 4-Hydroxypropranolol hydrochlorid inhibits β1- and β2-adrenergic receptors with pA2 values of 8.24 and 8.26, respectively. 4-Hydroxypropranolol hydrochlorid has intrinsic sympathomimetic activity, membrane stabilizing activity and potent antioxidant properties[1][2][3].

  • CAS Number: 14133-90-5
  • MF: C16H22ClNO3
  • MW: 311.804
  • Catalog: Adrenergic Receptor
  • Density: 1.168g/cm3
  • Boiling Point: 487.5ºC at 760mmHg
  • Melting Point: 156-158ºC
  • Flash Point: 248.6ºC

(Tyr0)-Urocortin (rat)

(Tyr0)-Urocortin, rat is a high-affinity agonist of corticotropin-releasing factor receptor type 1 (CRF-R1) and type 2 (CRF-R2). (Tyr0)-Urocortin, rat shows inhibitory binding constants (Ki) of 1-2 nM[1].

  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Oxetorone

Oxetorone fumarate is a non-selective, orally active serotonin antagonist. Oxetorone fumarate is an antimigraine agent[1].

  • CAS Number: 34522-46-8
  • MF: C25H25NO6
  • MW: 435.46900
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

1-[(2S)-2-Aminopropyl]-1H-indazol-6-ol

AL-34662 is a selective 5-HT2A receptoragonist (IC50: 0.77 nM and 1.5 nM for rat and human 5-HT2 receptor). AL-34662 is also a weak α-1D adrenergic agonist activity (EC50:0.4 μM). AL-34662 is an ocular hypotensive agent[1][2].

  • CAS Number: 210580-75-9
  • MF: C10H13N3O
  • MW: 191.23
  • Catalog: 5-HT Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 372.8±22.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 179.2±22.3 °C

Minecoside

Minecoside is a CXCR4/STAT3 inhibitor with anticancer and anti-inflammatory activity. Minecoside decreases CXCR4 expression and suppresses STAT3 activation, thus to inhibit CXCL 12-induced invasion. Minecoside potently inhibits cancer metastasis and promotes apoptotic progression[1][2].

  • CAS Number: 51005-44-8
  • MF: C25H30O13
  • MW: 538.50
  • Catalog: CXCR
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 815.9±65.0 °C at 760 mmHg
  • Melting Point: 142℃
  • Flash Point: 275.7±27.8 °C

NTNT 185

YNT-185 dihydrochloride is a nonpeptide, selective orexin type-2 receptor (OX2R) agonist, with EC50s of 0.028 and 2.75 μM for OX2R and OX1R, respectively. YNT-185 dihydrochloride ameliorates narcolepsy-cataplexy symptoms in mouse models[1][2].

  • CAS Number: 1804978-82-2
  • MF: C33H39Cl2N5O5S
  • MW: 688.66
  • Catalog: Orexin Receptor (OX Receptor)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(S)-Mapracorat

(S)-Mapracorat is a selective and less active glucocorticoid receptor agonist.

  • CAS Number: 887375-15-7
  • MF: C25H26F4N2O2
  • MW: 462.48
  • Catalog: Glucocorticoid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bevantolol hydrochloride

Bevantolol hydrochloride is a selective β1 and α1-adrenergic receptor antagonist with pKi values of 7.83, 6.9 in rat cerebral cortex, respectively. Bevantolol hydrochloride is a potent Ca2+ antagonist[1][2].

  • CAS Number: 42864-78-8
  • MF: C20H28ClNO4
  • MW: 381.894
  • Catalog: Adrenergic Receptor
  • Density: N/A
  • Boiling Point: 518.3°C
  • Melting Point: N/A
  • Flash Point: N/A

Adenylyl cyclase-IN-1

Adenylyl cyclase-IN-1 is an adenylyl cyclase inhibitor with potential use in ocular hypotonia research[1].

  • CAS Number: 731827-16-0
  • MF: C9H8N2S3
  • MW: 240.37
  • Catalog: Adenylate Cyclase
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 352.5±35.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 167.0±25.9 °C

SB 203186 hydrochloride

SB-203186 hydrochloride is a potent and competitive 5-HT4 antagonist. SB-203186 hydrochloride antagonizes the 5-HT4 receptor-mediated relaxations of the carbachol-contracted rat isolated oesophagus against 5-HT with pKB values of 10.9 (rat oesophagus), 9.5 (guinea-pig ileum), and 9.0 (human colon) respectively[1][2][3].

  • CAS Number: 207572-69-8
  • MF: C16H21ClN2O2
  • MW: 308.803
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

R 59-022 hydrochloride

R 59-022 (DKGI-I) hydrochloride is a DGK inhibitor (IC50: 2.8 µM). R 59-022 hydrochloride inhibits the phosphorylation of OAG to OAPA. R 59-022 hydrochloride is a 5-HT Receptor antagonist, and activates protein kinase C (PKC). R 59-022 hydrochloride potentiates thrombin-induced diacylglycerol production in platelets and inhibits phosphatidic acid production in neutrophils[1][2][3][4].

  • CAS Number: 93076-98-3
  • MF: C27H27ClFN3OS
  • MW: 496.04
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TM 38837

TM38837 is a peripheral selective cannabinoid receptor type 1 (CB1) receptor antagonist. TM38837 shows limited penetrance to the brain in order to minimize or prevent CNS adverse reactions, and preserves potential antiobesity effects. TM38837 reduces propensity for psychiatric side effects[1][2].

  • CAS Number: 1253641-65-4
  • MF: C30H25Cl2F3N4OS
  • MW: 617.512
  • Catalog: Cannabinoid Receptor
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PGJ2

Prostaglandin J2 (PGJ2), an endogenous metabolite of Prostaglandin D2 (PGD2; HY-101988), is a potent PGD2 receptor (DP) agonist with Kis of 0.9 nM and 6.6 nM for hDP and hCRTH2, respectively. Prostaglandin J2 stimulates intracellular cyclic AMP production with an EC50 value of 1.2 nM. Prostaglandin J2 induces oxidative stress and neuronal apoptosis. Prostaglandin J2 induces the accumulation/aggregation of ubiquitinated (Ub) proteins. Prostaglandin J2 is highly neurotoxic and potentially contributes to many neurodegenerative conditions, including Alzheimer's (AD) and Parkinson's diseases (PD)[1][2][3][4].

  • CAS Number: 60203-57-8
  • MF: C20H30O4
  • MW: 334.450
  • Catalog: Prostaglandin Receptor
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 521.7±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 283.4±26.6 °C

KRas G12C inhibitor 4

KRas G12C inhibitor 1 is a compound that inhibits KRas G12C, extracted from patent US 20180072723 A1.

  • CAS Number: 2206736-07-2
  • MF: C33H38ClN7O2
  • MW: 600.15
  • Catalog: Ras
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Darifenacin HBr

Darifenacin HBr(UK88525) is a selective M3 muscarinic receptor antagonist with pKi of 8.9.IC50 value: 8.9 (pKi) [1]Target: M3 receptorin vitro: Darifenacin exerts non-parallel rightward displacement of the agonist curve and also significant depression of the maximum response (+)-cis-Dioxolane produced concentration-dependent contraction of the isolated bladder of rat [1]. Darifenacin produces a concentration dependent increase in R123 (P-gp probe) accumulation in MDCK cells. Darifenacin stimulates ATPase activity in P-gp membrane in a clear concentration dependent response manner with an estimated ED50 value of 1.6?μM. Darifenacin (100 nM) shows a significantly greater permeability for darifenacin in the basolateral to apical direction resulting in an efflux ratio in BBMEC monolayers of approximately 2.6 [2].in vivo: Darifenacin produces dose-dependent inhibition of amplitude of volume-induced bladder contractions(VIBCAMP), producing 35% inhibition at dose of 283.3 nmol/kg and maximal inhibition of approximately 50–55% [1]. Darifenacin (0.1 mg/kg i.v.) reduces bladder afferent activity in both Aδ and C fibers in female Sprague-Dawley rats, the decrease in afferent spikes in C fibers may be more pronounced than that in Aδ fibers [3].

  • CAS Number: 133099-07-7
  • MF: C28H31BrN2O2
  • MW: 507.46
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: 614.3ºC at 760 mmHg
  • Melting Point: 228-230ºC
  • Flash Point: 325.3ºC

Olanzapine D3

Olanzapine D3 (LY170053 D3) is the deuterium labeled Olanzapine. Olanzapine is 5-HT2 and D1/D2 antagonist. Olanzapine is an antipsychotic agent with anticholinergic properties[1]. Olanzapine induces autophagy, mitochondrial damage and mitophagy in human SH-SY5Y neuronal cell line[2].

  • CAS Number: 786686-79-1
  • MF: C17H17D3N4S
  • MW: 315.45100
  • Catalog: Apoptosis
  • Density: 1.337g/cm3
  • Boiling Point: 476.035ºC at 760 mmHg
  • Melting Point: 188-190ºC
  • Flash Point: 241.697ºC

SLF1081851

SLF1081851 (16 d) is an effective Sphingolipid Transporter 2 (Spns2) (S1P transporter) inhibitor with an IC50 value of 1.93 μM (S1P), SLF1081851 inhibits SphK2 with an IC50 value of ≈ 30 μM (SphK2), and is at least 15-fold more selective for SphK2 than SphK1. SLF1081851 has the potential to investigate Spns2 biology and can be used for autoimmune encephalomyelitis (EAE) research[1].

  • CAS Number: 2763730-97-6
  • MF: C21H33N3O
  • MW: 343.51
  • Catalog: LPL Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

FLX475

FLX475 is a potent CCR4 antagonist that blocks regulatory T cells that interfere with effective antitumor immune responses and has antitumor activity[1].

  • CAS Number: 2174938-78-2
  • MF: C24H27Cl2F3N6O
  • MW: 543.41
  • Catalog: CCR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Prednisolone Sodium Phosphate

Prednisolone disodium phosphate is a synthetic glucocorticoid with anti-inflammatory and immunomodulating properties.Target: Glucocorticoid ReceptorPrednisolone irreversibly binds with glucocorticoid receptors (GR) alpha and beta for which they have a high affinity. Prednisolone can activate and influence biochemical behaviour of most cells. The steroid/receptor complexes dimerise and interact with cellular DNA in the nucleus, binding to steroid-response elements and modifying gene transcription. They induce synthesis of some proteins, and inhibit synthesis of others. Prednisolone exerted a delayed biphasic effect on the resistant CCRF-CEM leukemic cell line, necrotic at low doses and apoptotic at higher doses. At low doses, prednisolone exerted a pre-dominant mitogenic effect despite its induction on total cell death, while at higher doses, prednisolone's mitogenic and cell death effects were counterbalanced [1, 2].

  • CAS Number: 125-02-0
  • MF: C21H27Na2O8P
  • MW: 484.388
  • Catalog: Glucocorticoid Receptor
  • Density: N/A
  • Boiling Point: 100 °C
  • Melting Point: N/A
  • Flash Point: 361.9ºC

Asimadoline

Asimadoline is a potent κ opioid receptor agonist with IC50s of 5.6 and 1.2 nM for guinea pig and human recombinant κ opioid receptor, respectively.

  • CAS Number: 153205-46-0
  • MF: C27H30N2O2
  • MW: 414.539
  • Catalog: Opioid Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 605.8±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 320.2±31.5 °C

Adenosine receptor inhibitor 2

Adenosine receptor inhibitor 2 (compound 14b) is a potent AR (adenosine receptor) inhibitor. Adenosine receptor inhibitor 2 shows dual affinity toward A1/A2A ARs with higher affinity for the A1- than the A2AAR. Adenosine receptor inhibitor 2 has Ki values of 52.2 nM for the A1AR and 167 nM for the A2AAR[1].

  • CAS Number: 2550401-76-6
  • MF: C17H20BrN5O2
  • MW: 406.28
  • Catalog: Adenosine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bim 21009

Bim 21009 is an inhibitor of gonadorelin.

  • CAS Number: 106881-54-3
  • MF: C74H92ClN17O13
  • MW: 1463.08
  • Catalog: GNRH Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Manumycin A

Manumycin A is an antibiotic. Manumycin A acts as a selective, competitive inhibitor of protein farnesyltransferase (FTase) with respect to farnesylpyrophosphate (Ki =1.2 μM), and as a noncompetitive inhibitor with respect to the Ras protein. Manumycin A induces apoptosis and exerts antitumor activity[1] [2][3].

  • CAS Number: 52665-74-4
  • MF: C31H38N2O7
  • MW: 550.643
  • Catalog: Apoptosis
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 863.6±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 476.1±34.3 °C

LIT-001 free base

LIT-001 (LIT001) is the first nonpeptide Oxytocin receptor (OT-R) agonist with EC50 of 55 nM, Emax=96%; efficiently relieved social interaction deficits in Oprm1−/− mice, a mouse model of autism.

  • CAS Number: 2245072-20-0
  • MF: C28H33N7O2S
  • MW: 531.679
  • Catalog: Oxytocin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A