1. GPCR/G Protein
    Neuronal Signaling
  2. 5-HT Receptor
  3. RS-127445 hydrochloride

RS-127445 hydrochloride 

Cat. No.: HY-15419 Purity: 99.58%
Handling Instructions

RS-127445 hydrochloride is a selective, high affinity, orally bioavailable 5-HT2B receptor antagonist with a pKi of 9.5. RS-127445 hydrochloride shows 1000 fold selectivity for this receptor as compared to numerous other receptor and ion channel binding sites.

For research use only. We do not sell to patients.

RS-127445 hydrochloride Chemical Structure

RS-127445 hydrochloride Chemical Structure

CAS No. : 199864-86-3

Size Price Stock Quantity
Solution
10 mM * 1 mL in DMSO USD 66 In-stock
Estimated Time of Arrival: December 31
Solid + Solvent
10 mM * 1 mL
ready for reconstitution
USD 66 In-stock
Estimated Time of Arrival: December 31
Solid
5 mg USD 60 In-stock
Estimated Time of Arrival: December 31
10 mg USD 96 In-stock
Estimated Time of Arrival: December 31
50 mg USD 384 In-stock
Estimated Time of Arrival: December 31
100 mg   Get quote  
200 mg   Get quote  

* Please select Quantity before adding items.

Other Forms of RS-127445 hydrochloride:

Top Publications Citing Use of Products
  • Biological Activity

  • Protocol

  • Purity & Documentation

  • References

  • Customer Review

Description

RS-127445 hydrochloride is a selective, high affinity, orally bioavailable 5-HT2B receptor antagonist with a pKi of 9.5. RS-127445 hydrochloride shows 1000 fold selectivity for this receptor as compared to numerous other receptor and ion channel binding sites[1].

IC50 & Target

sPLA2

5.5 (pKi)

5-HT3 Receptor

<6 (pKi)

5-HT5 Receptor

<6 (pKi)

5-HT6 Receptor

<6 (pKi)

5-HT2A Receptor

6.3 (pKi)

5-HT2C Receptor

6.4 (pKi)

5-HT2B Receptor

9.5 (pKi)

In Vitro

RS-127445 is found to has nanomolar affinity for the 5-HT2B receptor (pKi=9.5±0.1) and 1,000 fold selectivity for this receptor as compared to numerous other receptor and ion channel binding sites. RS-127445 potently displaces [3H]-5-HT from human recombinant 5-HT2B receptors expressed in CHO-K1 cells. The affinity (pKi value) of RS-127445 for the 5-HT2B receptor is 9.5±0.1 (n=9). RS-127445 is selective for the 5-HT2B receptor, having approximately 1000 fold lower affinity for the human recombinant 5-HT2A, 5-HT2C, 5-HT5, 5-HT6 and 5-HT7 receptors, a 5-HT1A receptor in rat brain membranes, a 5-HT1B/D receptor in bovine caudate, and a monoamine uptake site in rabbit platelets. RS-127445 potently blocks the 5-HT (10 nM) evoked increases in intracellular calcium concentrations in the HEK-293 cells expressing the 5-HT2B receptor (pIC50 of 10.4±0.1). In cells expressing human recombinant 5-HT2B receptors, RS-127445 potently antagonizes 5-HT-evoked formation of inositol phosphates (pKB=9.5±0.1) and 5-HT-evoked increases in intracellular calcium (pIC10=10.4±0.1). RS-127445 also blocks 5-HT-evoked contraction of rat isolated stomach fundus (pA2B=9.5±1.1) and (±)α-methyl-5-HT-mediated relaxation of the rat jugular vein (pA2=9.9±0.3)[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

In rats, the fraction of RS-127445 that is bioavailable via the oral or intraperitoneal routes is 14 and 60% respectively. Intraperitoneal administration of RS-127445 (5 mg/kg) produced plasma concentrations predicted to fully saturate accessible 5-HT2B receptors for at least 4 h.RS-127445 (5 mg/kg) is administered to rats by oral, intraperitoneal and intravenous routes. Peak plasma concentrations are rapidly achieved with the highest concentrations being found at the first time-point measured following intravenous and intraperitonael administration (0.08 h) and by 0.25 h following dosing by the oral route of administration. RS-127445 is cleared from plasma with an estimated terminal elimination half-life of approximately 1.7 h. The bioavailability of RS-127445, when administered by the oral and intraperitoneal routes is approximately 14 and 62% of that obtained by intravenous administration. Approximately 60% of an intraperitoneal dose and 14% of the oral dose of RS-127445 (5 mg/kg) is bioavailable[1]. RS-127445 (1-30 mg/kg), dose-dependently reduces faecal output, reaching significance at 10 and 30 mg/kg (n=6-11). In blood and brain, >98% of RS-127445 is protein-bound[2].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Molecular Weight

317.79

Formula

C₁₇H₁₇ClFN₃

CAS No.
Shipping

Room temperature in continental US; may vary elsewhere.

Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
Solvent & Solubility
In Vitro: 

DMSO : ≥ 31 mg/mL (97.55 mM)

H2O : 2.27 mg/mL (7.14 mM; ultrasonic and warming and heat to 60°C)

*"≥" means soluble, but saturation unknown.

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 3.1467 mL 15.7337 mL 31.4673 mL
5 mM 0.6293 mL 3.1467 mL 6.2935 mL
10 mM 0.3147 mL 1.5734 mL 3.1467 mL
*Please refer to the solubility information to select the appropriate solvent.
In Vivo:
  • 1.

    Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% saline

    Solubility: ≥ 2.5 mg/mL (7.87 mM); Clear solution

  • 2.

    Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in saline)

    Solubility: ≥ 2.5 mg/mL (7.87 mM); Clear solution

  • 3.

    Add each solvent one by one:  10% DMSO    90% corn oil

    Solubility: ≥ 2.5 mg/mL (7.87 mM); Clear solution

*All of the co-solvents are provided by MCE.
References
Cell Assay
[1]

HEK-293 cells expressing the human 5-HT2B receptor are incubated with [3H]-myoinositol (1.67 μCi/mL) in 162 cm2 flasks overnight at 37°C in an inositol free Ham's F12 medium containing 10% dialyzed foetal bovine serum. The cells are harvested, washed five times with phosphate buffered saline and resuspended in inositol free Ham's F12 media at density of approximately 3×106 cells/mL. RS-127445 (10 μM) is initially dissolved in 10% (v/v) DMSO with 90% inositol free Ham's F12 medium. Subsequent dilutions are made with inositol free Ham's F12 medium. 5-HT is dissolved in inositol free Ham's F12 medium containing 100 mM LiCl and 1 mM ascorbate. RS-127445, vehicle or other antagonists are pre-incubated with 240 μL of cell suspension at 37°C for 20 min. The reactions are initiated by addition of 5-HT. Sixty minutes later, the reactions are terminated by adding 50 μL of ice-cold 20% perchloric acid, chilled in an ice-water bath for 10 min and then neutralized with 160 μL of 1 N KOH. Each sample is diluted with 2 ml of 50 mM Tris-HCl, pH 7.4 at room temperature. The aqueous portion (2.2 mL) is transferred onto Dowex AG1X8 columns (1 ml, 1 : 1, w/v) which had been washed with 5 ml of distilled water. The columns are then washed with 18 ml of distilled water and the inositol phosphates are eluted with 3 ml of 1 N HCl. The eluted radioactivity is determined by liquid scintillation spectroscopy using a Packard 1900CA analyzer[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[1][2]

Rats[1]
Male Sprague-Dawley rats (200 g) are used. To compare the plasma kinetics of RS-127445 following different routes of administration, 90 rats are distributed into three treatment groups of 30 rats each. A single dose of RS-127445 (5 mg/kg) dissolved (2.5 mg/mL) in ethanol:propylene glycol : water (10 : 50 : 40, v:v:v), is administered to each rat. At 0.08, 0.25, 0.5, 1, 2, 4, 8 and 24 h after dosing, the rats are anaesthetized and blood samples are collected by cardiac puncture.
Mice[2]
Adult male C57BL/6J mice (25-30 g) are used. The effects of RS-127445 (1 nM-10 µM, single concentration per tissue, 15 min contact time) or vehicle (5 or 50 µL DMSO) are expressed as the percentage change in amplitude compared with the mean amplitude of four pre-drug, post-EFS contractile responses. The results are analysed using a two-sample equal variance t-test.

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
  • No file chosen (Maximum size is: 1024 Kb)
  • If you have published this work, please enter the PubMed ID.
  • Your name will appear on the site.
  • Molarity Calculator

  • Dilution Calculator

The molarity calculator equation

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass   Concentration   Volume   Molecular Weight *
= × ×

The dilution calculator equation

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
× = ×
C1   V1   C2   V2

Your Recently Viewed Products:

Inquiry Online

Your information is safe with us. * Required Fields.

Product Name

 

Salutation

Applicant Name *

 

Email address *

Phone number *

 

Organization name *

Department *

 

Requested quantity *

Country or Region *

     

Remarks

Bulk Inquiry

Inquiry Information

Product Name:
RS-127445 hydrochloride
Cat. No.:
HY-15419
Quantity:
MCE Japan Authorized Agent: