Synonym
GR127935; GR 127935; GR-127935; GR 127935 HCl; GR 127935 hydrochloride;
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
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
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/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
1.0 |
1.87 |
| DMSO:PBS (pH 7.2) (1:1) |
0.3 |
0.47 |
| Water |
49.8 |
93.17 |
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
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.
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.
