GR 127935 HCl | CAS#148642-42-6 | 5-HT1B/1D receptor antagonist

GR 127935 HCl
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WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 531851

CAS#: 148642-42-6

Description: GR 127935 HCl is a potent and selective 5-HT1B/1D receptor antagonist (pKi values are 8.5 for both guinea pig 5-HT1D and rat 5-HT1B receptors). GR 127935 HCl displays > 100-fold selectivity over 5HT1A, 5-HT2A, 5-HT2C receptors and other receptor types.

Chemical Structure

GR 127935 HCl

CAS# 148642-42-6

Product data Instruction

Theoretical Analysis

MedKoo Cat#: 531851
Name: GR 127935 HCl
CAS#: 148642-42-6
Chemical Formula: C29H32ClN5O3
Exact Mass: 0.00
Molecular Weight: 534.057
Elemental Analysis: C, 65.22; H, 6.04; Cl, 6.64; N, 13.11; O, 8.99

Price and Availability

Size	Price	Availability
10mg	USD 350	2 Weeks
50mg	USD 950	2 Weeks
Bulk inquiry Welcome, Customer: Please do not inquire quote if your intended use is for a patient since our products are for research use and for chemical synthesis use, not for human use . For in-stock products, we listed price in the web page. You may inquire prices for which sizes were not listed. If no price is listed, this means the product is not in stock at the moment, which may be available via custom synthesis. For cost-effective reason, minimum order of 1g is requested (typically very expensive). The lead time is usually 2-4 months. Quote of less than 1g will not be provided. MedKoo may not offer quote for below reasons: (1) current available synthetic method appears to be extremely expensive which is obviously not affordable to most customers; (2) Key raw material to make the product is temporally not available; (3) DEA controlled substances; (4) the product is under patent protection in customer’s country.

Related CAS #: 148642-42-6 (HCl); 148672-13-3 (Free Base).

Synonym: GR 127935; GR-127935; GR 127935 HCl; GR 127935.

IUPAC/Chemical Name: N-[4-Methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)-1,1'-biphenyl-4-carboxamide hydrochloride

InChi Key: SRVVUYIJVBLEJI-UHFFFAOYSA-N

InChi Code: InChI=1S/C29H31N5O3.ClH/c1-19-17-23(28-30-20(2)37-32-28)9-11-25(19)21-5-7-22(8-6-21)29(35)31-24-10-12-27(36-4)26(18-24)34-15-13-33(3)14-16-34;/h5-12,17-18H,13-16H2,1-4H3,(H,31,35);1H

SMILES Code: O=C(C1=CC=C(C2=CC=C(C3=NOC(C)=N3)C=C2C)C=C1)NC4=CC=C(OC)C(N5CCN(C)CC5)=C4.[H]Cl

Appearance: Solid powder

Purity: >98% (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

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Product Data:

Product Data

Instruction:

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Biological target:	GR127935 hydrochloride is a potent and orally active 5-HT1D and 5-HT1B receptor antagonist with pKis of 8.5 for both isoforms.
In vitro activity:	Treatment of the AGS and SGC7901 GC cell lines with the HTR1D inhibitor GR127935 significantly and dose-dependently reduced the expression of HTR1D protein (Fig. S4) as well as cell growth (Fig. 3A), the number of colonies (Fig. 3B), and cell migration (Fig. 3C). Furthermore, treatment of cells with GR127935 showed consistent results with those of the HTR1D knockdown experiments. Moreover, the flow cytometry assay showed that the mechanism by which GR127935 inhibited GC cell proliferation was mediated through cell cycle arrest of AGS and SGC7901 cells in the G1 phase (Fig. 3D). Reference: Biochem Biophys Res Commun. 2022 Sep 10;620:143-149. https://pubmed.ncbi.nlm.nih.gov/35785570/
In vivo activity:	GR127935 significantly antagonized the effects of CSD-induced inhibition of the dural-evoked neuronal responses 10 minutes after injection (GR127935, t13 = 2.504, P = 0.026; Figure 4A), while the effect of naloxone was seen at 20 minutes (t13 = 3.471, P = 0.004, Figure 4B) respectively, when compared with inhibition of TCC neuronal firing in the control rat group. Reference: Cephalalgia. 2022 Jul 13:3331024221112998. https://pubmed.ncbi.nlm.nih.gov/35833238/

Solubility Data

	Solvent	Max Conc. mg/mL	Max Conc. mM
Solubility
	DMSO	1.0	1.87
	DMSO:PBS (pH 7.2) (1:1)	0.3	0.47
	Water	49.8	93.17

Preparing Stock Solutions

The following data is based on the product molecular weight 534.06 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. Jin X, Li H, Li B, Zhang C, He Y. Knockdown and inhibition of hydroxytryptamine receptor 1D suppress proliferation and migration of gastric cancer cells. Biochem Biophys Res Commun. 2022 Sep 10;620:143-149. doi: 10.1016/j.bbrc.2022.06.088. Epub 2022 Jun 28. PMID: 35785570. 2. Supronsinchai W, Hoffmann J, Akerman S, Goadsby PJ. KCl-induced repetitive cortical spreading depression inhibiting trigeminal neuronal firing is mediated by 5-HT1B/1D and opioid receptors. Cephalalgia. 2022 Jul 13:3331024221112998. doi: 10.1177/03331024221112998. Epub ahead of print. PMID: 35833238. 3. Hiraki Y, Araki R, Fujiwara H, Ago Y, Tanaka T, Toume K, Matsumoto K, Yabe T. Kamiuntanto increases prefrontal extracellular serotonin levels and ameliorates depression-like behaviors in mice. J Pharmacol Sci. 2019 Feb;139(2):72-76. doi: 10.1016/j.jphs.2018.11.008. Epub 2018 Nov 30. PMID: 30545726.
In vitro protocol:	1. Jin X, Li H, Li B, Zhang C, He Y. Knockdown and inhibition of hydroxytryptamine receptor 1D suppress proliferation and migration of gastric cancer cells. Biochem Biophys Res Commun. 2022 Sep 10;620:143-149. doi: 10.1016/j.bbrc.2022.06.088. Epub 2022 Jun 28. PMID: 35785570.
In vivo protocol:	1. Supronsinchai W, Hoffmann J, Akerman S, Goadsby PJ. KCl-induced repetitive cortical spreading depression inhibiting trigeminal neuronal firing is mediated by 5-HT1B/1D and opioid receptors. Cephalalgia. 2022 Jul 13:3331024221112998. doi: 10.1177/03331024221112998. Epub ahead of print. PMID: 35833238. 2. Hiraki Y, Araki R, Fujiwara H, Ago Y, Tanaka T, Toume K, Matsumoto K, Yabe T. Kamiuntanto increases prefrontal extracellular serotonin levels and ameliorates depression-like behaviors in mice. J Pharmacol Sci. 2019 Feb;139(2):72-76. doi: 10.1016/j.jphs.2018.11.008. Epub 2018 Nov 30. PMID: 30545726.

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1: Sánchez-Maldonado C, López-Sánchez P, Anguiano-Robledo L, Leopoldo M, Lacivita E, Terrón JA. GR-127935-sensitive mechanism mediating hypotension in anesthetized rats: are 5-HT5B receptors involved? J Cardiovasc Pharmacol. 2015 Apr;65(4):335-41. doi: 10.1097/FJC.0000000000000200. PubMed PMID: 25502305.

2: Uphouse L, Hiegel C, Guptarak J, Maswood N. Progesterone reduces the effect of the serotonin 1B/1D receptor antagonist, GR 127935, on lordosis behavior. Horm Behav. 2009 Jan;55(1):169-74. doi: 10.1016/j.yhbeh.2008.09.011. PubMed PMID: 18952090; PubMed Central PMCID: PMC2665997.

3: Chaouloff F, Courvoisier H, Moisan MP, Mormède P. GR 127935 reduces basal locomotor activity and prevents RU 24969-, but not D-amphetamine-induced hyperlocomotion, in the Wistar-Kyoto hyperactive (WKHA) rat. Psychopharmacology (Berl). 1999 Jan;141(3):326-31. PubMed PMID: 10027515.

4: Harrison AA, Parsons LH, Koob GF, Markou A. RU 24969, a 5-HT1A/1B agonist, elevates brain stimulation reward thresholds: an effect reversed by GR 127935, a 5-HT1B/1D antagonist. Psychopharmacology (Berl). 1999 Jan;141(3):242-50. PubMed PMID: 10027505.

5: Chaouloff F, Aguerre S, Mormede P. GR 127935 and (+)-WAY 100135 do not affect TFMPP-induced inhibition of 5-HT synthesis in the midbrain and hippocampus of Wistar-Kyoto rats. Neuropharmacology. 1998 Sep;37(9):1159-67. PubMed PMID: 9833646.

6: Villalón CM, Centurión D, Luján-Estrada M, Terrón JA, Sánchez-López A. Mediation of 5-HT-induced external carotid vasodilatation in GR 127935-pretreated vagosympathectomized dogs by the putative 5-HT7 receptor. Br J Pharmacol. 1997 Apr;120(7):1319-27. PubMed PMID: 9105708; PubMed Central PMCID: PMC1564589.

7: De Vries P, Heiligers JP, Villalón CM, Saxena PR. Blockade of porcine carotid vascular response to sumatriptan by GR 127935, a selective 5-HT1D receptor antagonist. Br J Pharmacol. 1996 May;118(1):85-92. PubMed PMID: 8733580; PubMed Central PMCID: PMC1909483.

8: O'Neill MF, Fernández AG, Palacios JM. GR 127935 blocks the locomotor and antidepressant-like effects of RU 24969 and the action of antidepressants in the mouse tail suspension test. Pharmacol Biochem Behav. 1996 Mar;53(3):535-9. PubMed PMID: 8866952.

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GR 127935 HCl featured