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.


Anti-infection >
Arenavirus Bacterial CMV Enterovirus Filovirus Fungal HBV HCV HIV HSV Influenza Virus Parasite Reverse Transcriptase RSV SARS-CoV
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15-PGDH 5 alpha Reductase 5-Lipoxygenase Acetyl-CoA Carboxylase Acyltransferase Adenosine Deaminase Adenosine Kinase Aldehyde Dehydrogenase (ALDH) Aldose Reductase Aminopeptidase Angiotensin-converting Enzyme (ACE) ATGL ATP Citrate Lyase Carbonic Anhydrase Carboxypeptidase Cathepsin CETP COMT Cytochrome P450 Dipeptidyl Peptidase Dopamine β-hydroxylase E1/E2/E3 Enzyme Elastase Enolase FAAH FABP Factor Xa Farnesyl Transferase Fatty Acid Synthase (FAS) FXR Glucokinase GSNOR Gutathione S-transferase HCV Protease Hexokinase HIF/HIF Prolyl-Hydroxylase HIV Integrase HIV Protease HMG-CoA Reductase (HMGCR) HSP Indoleamine 2,3-Dioxygenase (IDO) Isocitrate Dehydrogenase (IDH) Lactate Dehydrogenase LXR MAGL Mineralocorticoid Receptor Mitochondrial Metabolism MMP Nampt NEDD8-activating Enzyme Neprilysin PAI-1 PDHK PGC-1α Phosphatase Phosphodiesterase (PDE) Phospholipase Procollagen C Proteinase Proteasome Pyruvate Kinase RAR/RXR Renin ROR Ser/Thr Protease SGK Stearoyl-CoA Desaturase (SCD) Thrombin Tryptophan Hydroxylase Tyrosinase Xanthine Oxidase
Neuronal Signaling >
5-HT Receptor AChE Adenosine Kinase Amyloid-β Beta-secretase CaMK CGRP Receptor COMT Dopamine Receptor Dopamine Transporter FAAH GABA Receptor GlyT iGluR Imidazoline Receptor mAChR Melatonin Receptor Monoamine Oxidase nAChR Neurokinin Receptor Opioid Receptor Serotonin Transporter γ-secretase
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Maraviroc

Maraviroc is a selective CCR5 antagonist with activity against human HIV.

  • CAS Number: 376348-65-1
  • MF: C29H41F2N5O
  • MW: 513.666
  • Catalog: HIV
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: 79-81ºC
  • Flash Point: N/A

JNJ-18038683

JNJ-18038683 is a 5-Hydroxytryptamine Type 7 (5-HT7) receptor antagonist, with pKis of 8.19, 8.20 for rat and human 5-HT7 in HEK293 cells, respectively.

  • CAS Number: 851376-05-1
  • MF: C26H28ClN3O7
  • MW: 529.97
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MCH(human, mouse, rat)

MCH (human, mouse, rat) is a potent peptide agonist of MCH-R and exhibits binding IC50 values of 0.3nM and 1.5 nM for MCH1R and MCH2R, respectively. MCH (human, mouse, rat) is a highly sensitive to MCH-2R in a CHO cell line and monitoring mobilization of intracellular calcium with FLIPR, exhibits functional activation EC50 values of 3.9 nM and 0.1nM for human MCH-1R and MCH-2R, respectively[1].

  • CAS Number: 128315-56-0
  • MF: C105H160N30O26S4
  • MW: 2386.84000
  • Catalog: MCHR1 (GPR24)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Atrial Natriuretic Factor (1-28) (human) acetate salt

Atrial Natriuretic Peptide (ANP) (1-28), human, porcine is a 28-amino acid hormone, that is normally produced and secreted by the human heart in response to cardiac injury and mechanical stretch. ANP (1-28) inhibits endothelin-1 secretion in a dose-dependent way.

  • CAS Number: 89213-87-6
  • MF: C127H203N45O39S3
  • MW: 3080.444
  • Catalog: Peptides
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

S1P5 receptor agonist-1

S1P5 receptor agonist-1 (example 6) is a potent and selective agonist of S1P5 receptor with an EC50 value of 20 nM[1].

  • CAS Number: 2373330-78-8
  • MF: C20H24F3NO3
  • MW: 383.40
  • Catalog: LPL Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

RU 24969

RU 24969 is a selective agonist at the 5-HT1A and 5-HT1B receptors; IC50 value:Target: 5-HT1A/1B agonistRU 24969 possesses preference for the purported 5-HT1B subtype of central 5-HT1 recognition site. The reported significant linear correlation between hypotensive activity following intravenous (i.v.) administration to anesthetized rats and affinity for the central 5-HT1 binding site could only be maintained by incorporation of the affinity of RU 24969 for its low and 8-OH-DPAT for its high affinity binding site [1]. The drug RU 24969 (10 mg/kg) inhibited the rate of synthesis of 5-HT in rat brain by about 50%. Pretreatment of rats with desmethylimipramine over a longer term or clenbuterol given acutely, treatments known to enhance the behavioural responses of rats to various other 5-HT agonists, did not alter the RU 24969-induced response [2]. RU 24969 (0.03-3.0mg/kg, s.c.) dose-dependently decreased water consumption in water deprived rats [3].

  • CAS Number: 66611-26-5
  • MF: C14H16N2O
  • MW: 228.29000
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Methapyrilene Hydrochloride

Methapyrilene (Thenylpyramine) hydrochloride is an orally active H1-receptor antihistamine and an anticholinergic agent of the pyridine chemical class. Methapyrilene hydrochloride has hepatotoxicity and can be used as a hepatotoxin that cause periportal hepatic necrosis in vivo[2]

  • CAS Number: 135-23-9
  • MF: C14H20ClN3S
  • MW: 297.84700
  • Catalog: Histamine Receptor
  • Density: 1.148g/cm3
  • Boiling Point: 389.6ºC at 760 mmHg
  • Melting Point: 162°
  • Flash Point: 189.4ºC

BMY 14802 hydrochloride

BMY-14802 hydrochloride (BMY-14802-1) is a selective and orally active sigma receptor antagonist with an IC50 of 112 nM. BMY-14802 hydrochloride is also a 5-HT1A and adrenergic α1 receptors agonist. BMY-14802 hydrochloride has antipsychotic effects[1][2][3].

  • CAS Number: 105565-55-7
  • MF: C18H23ClF2N4O
  • MW: 384.85100
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: 520.8ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 268.8ºC

Suramin

Suramin is a polysulfonated naphthylurea with various biological activities. Suramin is a DNA topoisomerase II inhibitor with an IC50 of 5 μM.

  • CAS Number: 145-63-1
  • MF: C51H40N6O23S6
  • MW: 1297.28000
  • Catalog: P2Y Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TUG-424

TUG-424 is a potent and selective free fatty acid receptor 1 (FFA1/GPR40) agonist with an EC50 of 32 nM. TUG-424 significantly increases glucose-stimulated insulin secretion at 100 nM. TUG-424 may serve to explore the role of FFA1 in metabolic diseases such as diabetes or obesity[1].

  • CAS Number: 1082058-99-8
  • MF: C18H16O2
  • MW: 264.318
  • Catalog: GPR40
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 448.1±38.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 205.9±21.4 °C

ONO-7300243

ONO-7300243 is a novel, potent lysophosphatidic acid receptor 1 (LPA1) antagonist with IC50 of 0.16 μM.

  • CAS Number: 638132-34-0
  • MF: C28H31NO5
  • MW: 461.549
  • Catalog: LPL Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 688.1±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 369.9±31.5 °C

Alaproclate HCl

Alaproclate (GEA 654) hydrochloride is a selective and orally active serotonin re-uptake inhibitor (SSRI). Alaproclate hydrochloride also acts as a potent, reversible and noncompetitive antagonist of the NMDA receptor coupled ion flow[1][2].

  • CAS Number: 60719-83-7
  • MF: C13H19Cl2NO2
  • MW: 292.20
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: 324.8ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 150.2ºC

Mirabegron

Mirabegron is a selective β3-adrenoceptor agonist with EC50 of 22.4 nM.

  • CAS Number: 223673-61-8
  • MF: C21H24N4O2S
  • MW: 396.506
  • Catalog: Adrenergic Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 690.0±55.0 °C at 760 mmHg
  • Melting Point: 138-140°C
  • Flash Point: 371.1±31.5 °C

ZD-1611

ZD-1611 is a potent, orally active, selective ETA receptor antagonist, used for the research of ischemic stroke.

  • CAS Number: 186497-38-1
  • MF: C22H24N4O5S
  • MW: 456.515
  • Catalog: Endothelin Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 653.9±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 349.3±34.3 °C

Nifeviroc

Nifeviroc is an orally active CCR5 antagonist. Nifeviroc is used for the study of HIV type-1 infection[1].

  • CAS Number: 934740-33-7
  • MF: C33H42N4O6
  • MW: 590.710
  • Catalog: HIV
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 761.1±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 414.1±32.9 °C

Thonzylamine

Thonzylamine is an orally active H1 histamine receptor antagonist, exhibits good antihistaminic and antianaphylactic properties. Thonzylamine can be used for the research of hypersensitivity diseases, nasal congestion, allergic conjunctivitis and other allergic diseases[1][2].

  • CAS Number: 91-85-0
  • MF: C16H22N4O
  • MW: 286.37200
  • Catalog: Histamine Receptor
  • Density: 1.121g/cm3
  • Boiling Point: 440.6ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 220.3ºC

Clemastine fumarate

Clemastine Fumarate is a selective histamine H1 receptor antagonist with IC50 of 3 nM.Target: Histamine H1 ReceptorClemastine Fumarate inhibits histamine induced rise in [Ca2+]i in HL-60 cells with an IC50 of 3 nM as compared with that of chlorpheniramine or diphenhydramine with IC50 values of 20 nM and 100 nM, respectively [1]. Clemastine showed a first-pass reduction in the extent of absorption, with oral bioavailability calculated as 39.2 +/- 12.4%. Extravascular distribution of drug was suggested by the high volume of distribution (799 +/- 315 L) and low Cmax (0.577 +/- 0.252 ng/mL/mg) observed at 4.77 +/- 2.26 hours after administration, and by the biphasic decline in plasma concentration. The terminal elimination half-life (t1/2) of clemastine was 21.3 +/- 11.6 hours. Steady-state concentrations of clemastine were consistent with linear pharmacokinetic processes, and clearance was unaffected by age in the range studied, or by race [2].

  • CAS Number: 14976-57-9
  • MF: C25H30ClNO5
  • MW: 459.962
  • Catalog: Autophagy
  • Density: 1.097 g/cm3
  • Boiling Point: 116 °C / 24mmHg
  • Melting Point: 61 °C
  • Flash Point: 211ºC

UCM-1306

UCM-1306 is a potent and orally active human dopamine D1 receptor allosteric modulator (PAM). UCM-1306 increases the endogenous dopamine (DA) maximal effect both in human and mouse D1 receptors. UCM-1306 not only for improving motor symptoms but also for addressing the key comorbid cognitive impairment associated with long-term Parkinson’s disease (PD)[1].

  • CAS Number: 2258608-78-3
  • MF: C14H14FNO2S
  • MW: 279.33
  • Catalog: Dopamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DAU 5884 hydrochloride

DAU 5884 hydrochloride is a potent muscarinic M3 receptor antagonist. DAU 5884 hydrochloride inhibits methacholine-dependent effects on cell proliferation and muscle contractility[1].

  • CAS Number: 131780-48-8
  • MF: C17H22ClN3O3
  • MW: 351.83
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: 463 °C
  • Melting Point: N/A
  • Flash Point: N/A

CB1/2 agonist 2

CB1/2 agonist 2 (compound 23) is a potent non-selective cannabinoid ligand, with Ki values of 3.5 and 1.2 nM, respectively. CB1/2 agonist 2 can behave as a full CB1 agonist and CB2 competitive inverse agonist. CB1/2 agonist 2 shows antinociceptive activity[1].

  • CAS Number: 2772379-97-0
  • MF: C26H43NO3
  • MW: 417.62
  • Catalog: Cannabinoid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

IPAG

IPAG is a potent sigma-1 receptor antagonist with a pKi of 4.3[1]. IPAG induces apoptosis[2].

  • CAS Number: 193527-91-2
  • MF: C17H22IN3
  • MW: 395.28
  • Catalog: Sigma Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SR-31747

SR-31747 is a sigma ligand with immunosuppressive and anti-inflammatory properties. SR-31747 blocks cell proliferation by inhibiting sterol isomerase[1][2].

  • CAS Number: 132173-07-0
  • MF: C23H35Cl2N
  • MW: 396.43700
  • Catalog: Sigma Receptor
  • Density: N/A
  • Boiling Point: 479.9ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 244.1ºC

Cimbuterol

Cimbuterol is a β-adrenergic receptor agonist[1].

  • CAS Number: 54239-39-3
  • MF: C13H19N3O
  • MW: 233.31
  • Catalog: Adrenergic Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 189-191°C
  • Flash Point: N/A

PSB 0788

PSB-0788 (compound 17), xanthine-8-yl-benzenesulfonamide derivative, is a new selective high-affinity A2B antagonist with IC50 value of 3.64 nM and Ki value of 0.393 nM, respeactively. PSB-0788 (compound 17) can be used for the research for chronic inflammatory lung diseases[1].

  • CAS Number: 1027513-54-7
  • MF: C25H27ClN6O4S
  • MW: 543.03800
  • Catalog: Adenosine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Salmeterol

Salmeterol is a long-acting beta2-adrenergic receptor (beta 2AR) agonist used clinically to treat asthma.Target: beta2-Adrenergic ReceptorSalmeterol is a long-acting beta2-adrenergic receptor agonist drug that is prescribed for the treatment of asthma and chronic obstructive pulmonary disease (COPD). salmeterol also binds with very high affinity at a second site, termed the "exosite", and that this exosite contributes to the long duration of action of salmeterol [1].

  • CAS Number: 89365-50-4
  • MF: C25H37NO4
  • MW: 415.566
  • Catalog: Adrenergic Receptor
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 603.0±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 318.5±31.5 °C

Hemorphin-7

Hemorphin-7 is a hemorphin peptide, an endogenous opioid peptide derived from the β-chain of hemoglobin. Hemorphin peptides exhibits antinociceptive and antihypertensive activities, activating opioid receptors and inhibiting angiotensin-converting enzyme (ACE).

  • CAS Number: 152685-85-3
  • MF: C49H64N12O11
  • MW: 997.106
  • Catalog: Peptides
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Carbazochrome sodium sulfonate (AC-17)

Carbazochrome(AC-17) is an antihemorrhagic agent.Target: OthersCarbazochrome is an antihemorrhagic agent that will cease blood flow by causing the aggregation and adhesion of platelets in the blood to form a platelet plug, ceasing blood flow from an open wound. It is hoped that this drug can be used in the future for preventing excessive blood flow during surgical operations and the treatment of hemorrhoids. Carbazochrome interacts with α-adrenoreceptors on surface of platelets, which are coupled to Gq protein and initiate PLC IP3/DAG pathway to increase intracellular free calcium concentration with these subsequent actions. Activates PLA2 and induce arachidonic acid pathway to synthese endoperoxides (TxA2, thromboxane A2). Calcium binds to calmodulin which then binds and activates myosin light-chain kinase, that will enable the myosin crossbridge to bind to the actin filament and allow contraction to begin. This will change platelet's shape and induce release of serotonin, ADP, vWF (Von Willebrand factor), PAF (Platelet-activating factor) to promote further aggregation and adhesion. From Wikipedia.

  • CAS Number: 51460-26-5
  • MF: C10H11N4NaO5S
  • MW: 322.27
  • Catalog: Adrenergic Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bevenopran

Bevenopran is a peripheral μ-opioid receptor antagonist.

  • CAS Number: 676500-67-7
  • MF: C20H26N4O4
  • MW: 386.44500
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

KRAS G12C inhibitor 26

KRAS G12C inhibitor 26 is a KRAS G12C inhibitor with antitumor effects (WO2021109737)[1].

  • CAS Number: 2648584-52-3
  • MF: C29H32F4N6O3
  • MW: 588.60
  • Catalog: Ras
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

2-(4-(2-(4-(2,2-DIMETHYLBUTYL)-1H-IMIDAZOL-2-YL)ETHYL)PHENYL)PYRIDINE

BRS-3 receptor agonist-2 (compound 2) is a potent BRS-3 receptor agonist, with an EC50 of 2.5 nM for mouse BRS-3 receptor[1].

  • CAS Number: 1021937-07-4
  • MF: C22H27N3
  • MW: 333.47
  • Catalog: Bombesin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A