GR-73632 | CAS#133156-06-6 | NK1 receptor agonist

MedKoo Cat#: 530303 | Name: GR-73632

Description:

WARNING: This product is for research use only, not for human or veterinary use.

GR-73632 is a selective tachykinin NK1 receptor agonist structurally derived from the neuropeptide substance P, designed to mimic its binding affinity and functional activity. It activates NK1 receptors by promoting Gq/11 protein-coupled signaling, leading to phospholipase C activation, IP3 generation, and intracellular calcium mobilization. GR-73632 has been studied for its ability to induce emesis and modulate gastrointestinal motility and central nervous system responses in preclinical models.

Chemical Structure

GR-73632

CAS#133156-06-6 (free base)

Theoretical Analysis

MedKoo Cat#: 530303

Name: GR-73632

CAS#: 133156-06-6 (free base)

Chemical Formula: C40H59N7O6S

Exact Mass: 765.4248

Molecular Weight: 766.02

Elemental Analysis: C, 62.72; H, 7.76; N, 12.80; O, 12.53; S, 4.19

Price and Availability

Size	Price	Availability
5mg	USD 350.00	2 Weeks
10mg	USD 650.00	2 Weeks
1g	USD 3,650.00	4 Weeks

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Related CAS #

GR73632 (acetate) 133156-06-6 (free base)

Synonym

GR-73632; GR 73632; GR73632

IUPAC/Chemical Name

(2S)-N-[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]-1-[(2S)-2-[[(2S)-2-(5-aminopentanoylamino)-3-phenylpropanoyl]amino]-3-phenylpropanoyl]-N-methylpyrrolidine-2-carboxamide

InChi Key

HQKPTSSZOJLFBZ-LJADHVKFSA-N

InChi Code

InChI=1S/C40H59N7O6S/c1-27(2)24-34(38(51)44-30(36(42)49)20-23-54-4)46(3)40(53)33-18-13-22-47(33)39(52)32(26-29-16-9-6-10-17-29)45-37(50)31(25-28-14-7-5-8-15-28)43-35(48)19-11-12-21-41/h5-10,14-17,27,30-34H,11-13,18-26,41H2,1-4H3,(H2,42,49)(H,43,48)(H,44,51)(H,45,50)/t30-,31-,32-,33-,34-/m0/s1

SMILES Code

CSCC[C@@H](C(N)=O)NC([C@H](CC(C)C)N(C([C@H]1N(C([C@H](CC2=CC=CC=C2)NC([C@H](CC3=CC=CC=C3)NC(CCCCN)=O)=O)=O)CCC1)=O)C)=O

Appearance

Solid powder

Purity

>95% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

GR-73632 is a novel tachykinin neurokinin 1 (NK-1) receptor agonist.

In vitro activity:

The selective NK1R agonist, GR73632, and Substance-P (SP) inhibited NE transport and reduced plasma membrane expression of NET and NK1R. Pretreatment with the NK1R antagonist, EMEND (aprepitant) prevented these NK1R-mediated effects. Reference: J Biol Chem. 2013 Oct 4;288(40):28599-610. https://pubmed.ncbi.nlm.nih.gov/23979140/

In vivo activity:

Netupitant (0.5, 1, 5, and 10 mg/kg, i.p.) caused a dose-dependent decrease in the frequency of vomits induced by the NK1R selective agonist GR73632 [(KW (4, = 23.13, p = 0.0001)] with significant reduction occurring at its 5 (p = 0.0009) and complete blockade at its 10 mg/kg dose (p = 0.0003) (Fig. 1A). The chi square test indicates that the percentage of shrews vomiting in response to GR73632 was also reduced by netupitant in a dose-dependent manner [(χ2 (4, 25) = 21.18, p = 0.0003)], with a significant reduction noted at its 5 (p = 0.0034) and complete protection occurring at its 10 mg/kg dose (p = 0.0005) (Fig. 1B). Reference: Neurochem Int. 2019 Jan;122:106-119. https://pubmed.ncbi.nlm.nih.gov/30453005/

	Solvent	mg/mL	mM
Solubility
	Water	1.0	1.31

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 766.02 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Arapulisamy O, Mannangatti P, Jayanthi LD. Regulated norepinephrine transporter interaction with the neurokinin-1 receptor establishes transporter subcellular localization. J Biol Chem. 2013 Oct 4;288(40):28599-610. doi: 10.1074/jbc.M113.472878. Epub 2013 Aug 26. PMID: 23979140; PMCID: PMC3789959. 2. Zhong W, Chebolu S, Darmani NA. Intracellular emetic signaling cascades by which the selective neurokinin type 1 receptor (NK1R) agonist GR73632 evokes vomiting in the least shrew (Cryptotis parva). Neurochem Int. 2019 Jan;122:106-119. doi: 10.1016/j.neuint.2018.11.012. Epub 2018 Nov 16. PMID: 30453005; PMCID: PMC6294657. 3. Ray AP, Chebolu S, Ramirez J, Darmani NA. Ablation of least shrew central neurokinin NK1 receptors reduces GR73632-induced vomiting. Behav Neurosci. 2009 Jun;123(3):701-6. doi: 10.1037/a0015733. PMID: 19485577; PMCID: PMC2714262.

In vitro protocol:

In vivo protocol:

1. Zhong W, Chebolu S, Darmani NA. Intracellular emetic signaling cascades by which the selective neurokinin type 1 receptor (NK1R) agonist GR73632 evokes vomiting in the least shrew (Cryptotis parva). Neurochem Int. 2019 Jan;122:106-119. doi: 10.1016/j.neuint.2018.11.012. Epub 2018 Nov 16. PMID: 30453005; PMCID: PMC6294657. 2. Ray AP, Chebolu S, Ramirez J, Darmani NA. Ablation of least shrew central neurokinin NK1 receptors reduces GR73632-induced vomiting. Behav Neurosci. 2009 Jun;123(3):701-6. doi: 10.1037/a0015733. PMID: 19485577; PMCID: PMC2714262.

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PubMed PMID: 23979140; PubMed Central PMCID: PMC3789959. 6: Kassick AJ, Jiang J, Bunda J, Wilson D, Bao J, Lu H, Lin P, Ball RG, Doss GA, Tong X, Tsao KL, Wang H, Chicchi G, Karanam B, Tschirret-Guth R, Samuel K, Hora DF, Kumar S, Madeira M, Eng W, Hargreaves R, Purcell M, Gantert L, Cook J, DeVita RJ, Mills SG. 2-[(3aR,4R,5S,7aS)-5-{(1S)-1-[3,5-bis(trifluoromethyl)phenyl]-2-hydroxyethoxy}-4- (2-methylphenyl)octahydro-2H-isoindol-2-yl]-1,3-oxazol-4(5H)-one: a potent human NK1 receptor antagonist with multiple clearance pathways. J Med Chem. 2013 Jul 25;56(14):5940-8. doi: 10.1021/jm400751p. PubMed PMID: 23808489. 7: Yoshino-Furukawa T, Maeda Y, Kikuchi A, Sakuma H, Imazumi K, Yamakuni H, Sogabe H, Matsuo M, Manda T, Uchida W. Pharmacological properties of FK886, a new, centrally active neurokinin-1 receptor antagonist. Biol Pharm Bull. 2013;36(1):76-81. PubMed PMID: 23302639. 8: Darmani NA, Chebolu S, Amos B, Alkam T. 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