| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| Other Sizes |
|
Purity: ≥98%
GR127935 HCl (GR-127935; GR 127935) is a novel, highly potent and selective 5-HT1B/1D receptor antagonist with pKis of 8.5 for both guinea pig 5-HT1D and rat 5-HT1B receptors. GR 127935 HCl demonstrates selectivity over 5HT1A, 5HT2A, 5-HT2C, and additional receptor types that is >100-fold.
| Targets |
5-HT1B Receptor ( pKi = 8.5 ); 5-HT1D Receptor ( pIC50 = 8.5 )
|
|---|---|
| ln Vitro |
The present study assessed the effects of HTR1D knockdown and the HTR1D inhibitor GR127935 on the biological behavior of GC cells, which both impaired the proliferation and migration of GC cells. RNA sequencing showed that GR127935 inhibited tumor progression by limiting DNA replication and the cell cycle, inducing ferroptosis, and affecting tumor metabolism. Taken together, these findings showed that HTR1D has a potent oncogenic effect on GC and may provide a novel therapeutic target.
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). [Biochem Biophys Res Commun. 2022 Sep 10:620:143-149.] |
| ln Vivo |
Harmaline (HA) induced impairment of memory acquisition.[2]
Higher dose of CP94253, GR127935, α-methyl 5-HT and cinancerine induced amnesia. [2] Subthreshold dose of CP94253 and GR127935 reversed HA induced amnesia. [2] Subthreshold dose of α-methyl 5-HT and cinancerine potentiated HA-induced amnesia. [2] Moreover, intra-CA1 administration of 5-HT1B/1D receptor agonist, CP94253 (5 ng/mouse), 5-HT1B/1D receptor antagonist, GR127935 (0.05 and 0.5 ng/mouse), 5-HT2A/2B/2C receptor agonist, α-methyl 5-HT (0.5 ng/mouse) and 5-HT2 receptor antagonist, cinancerine (0.5 ng/mouse) impaired memory acquisition, but did not affect locomotor activity and tail flick. Furthermore, pre-training intra-CA1 injection of subthreshold dose of CP94253 (0.05 ng/mouse) or GR127935 (0.005 ng/mouse) reversed impairment of memory acquisition induced by harmaline (1 mg/kg, i.p.). However, pre-training intra-CA1 infusion of subthreshold dose of α-methyl 5-HT (0.005 ng/mouse) or cinancerine (0.005 ng/mouse) with the administration of harmaline (0.5 and 1 mg/kg, i.p.) heighten impairment of memory acquisition. These findings implicate the involvement of CA1 serotonergic mechanism in harmaline-induced impairment of memory acquisition.[2] |
| Cell Assay |
Cell viability and cloning assay[Biochem Biophys Res Commun. 2022 Sep 10:620:143-149.]
Cells were seeded into 96-well plates at a density of 2000 cells/well and the viability was evaluated using the cell counting kit-8 reagent, according to the manufacturer's instructions. For cloning assays, 700 cells were seeded in each well of a six-well dish and cultured. When the colonies were visible to the naked eye (approximately 2 weeks), they were fixed with 4% paraformaldehyde and stained with crystal violet. Cell cycle analysis[Biochem Biophys Res Commun. 2022 Sep 10:620:143-149.] Cells treated with GR127935 were collected in 1.5-mL centrifuge tubes, washed once with PBS, and centrifuged. After discarding the supernatants, 1 mL DNA staining solution and 10 μL permeabilization solution were added to each tube, followed by incubation in the dark at room temperature for 30 min. The cells were subsequently assorted using flow cytometry. Cell migration assay[Biochem Biophys Res Commun. 2022 Sep 10:620:143-149.] Cell migration assays were performed using 24-well Transwell plates with 8-μm sized pores. A total of 5 × 104 cells in 200 μL FBS-free medium were added to each upper chamber and 700 μL medium containing 10% FBS was added to each lower chamber. After incubation for 24 h, the chambers were cleaned with PBS and fixed with 4% paraformaldehyde. The cells in the upper chamber were wiped with cotton balls, whereas those in the lower chamber that had migrated were stained with Giemsa. |
| Animal Protocol |
Mice weighing 25–30 g (5–8 weeks old animals) were kept in an animal house with a controlled temperature of 22 ± 2 °C under a 12/12-h light/dark cycle. Animals were housed in groups of 10 in Plexiglas cages and they had free access to water and food except during the limited times of experiments. Ten mice were used in each group and each animal was used once only. Behavioral tests were performed during the light phase of the light/dark cycle. All animal experiments reported in this study were conducted in accordance with the institutional guidelines for animal care and use.[2]
|
| References |
|
| Additional Infomation |
GR 127935 hydrochloride is a hydrochloride obtained by reaction of GR 127935 with one equivalent of hydrochloric acid. Potent and selective 5-HT1B/1D receptor antagonist (pKi values are 8.5 for both guinea pig 5-HT1D and rat 5-HT1B receptors). Displays > 100-fold selectivity over 5HT1A, 5-HT2A, 5-HT2C receptors and other receptor types. Centrally active following oral administration. It has a role as a serotonergic antagonist. It contains a GR 127935(1+).
|
| Molecular Formula |
C29H32CLN5O3
|
|---|---|
| Molecular Weight |
534.0491
|
| Exact Mass |
533.219
|
| Elemental Analysis |
C, 65.22; H, 6.04; Cl, 6.64; N, 13.11; O, 8.99
|
| CAS # |
148642-42-6
|
| Related CAS # |
148642-42-6 (HCl); 148672-13-3 (Free Base)
|
| PubChem CID |
11497466
|
| Appearance |
White to off-white solid powder
|
| LogP |
5.911
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
38
|
| Complexity |
739
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
Cl[H].O(C([H])([H])[H])C1C([H])=C([H])C(=C([H])C=1N1C([H])([H])C([H])([H])N(C([H])([H])[H])C([H])([H])C1([H])[H])N([H])C(C1C([H])=C([H])C(=C([H])C=1[H])C1C([H])=C([H])C(C2=NOC(C([H])([H])[H])=N2)=C([H])C=1C([H])([H])[H])=O
|
| 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
|
| Chemical Name |
N-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]-4-[2-methyl-4-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]benzamide;hydrochloride
|
| Synonyms |
GR 127935; GR-127935; GR 127,935; GR 127935 HCl; GR-127,935; GR 127935 hydrochloride; 148642-42-6; GR 127935 hydrochloride hydrate; GR 127935 HCl; GR127935 hydrochloride; GR127935 (hydrochloride); 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; CHEBI:64111; GR 127935
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8725 mL | 9.3624 mL | 18.7248 mL | |
| 5 mM | 0.3745 mL | 1.8725 mL | 3.7450 mL | |
| 10 mM | 0.1872 mL | 0.9362 mL | 1.8725 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA