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

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.

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RS-127445 hydrochloride Chemical Structure

RS-127445 hydrochloride Chemical Structure

CAS No. : 199864-86-3

Size Price Stock Quantity
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO
ready for reconstitution
USD 63 In-stock
Solution
10 mM * 1 mL in DMSO USD 63 In-stock
Solid
5 mg USD 58 In-stock
10 mg USD 87 In-stock
25 mg USD 174 In-stock
50 mg USD 262 In-stock
100 mg USD 393 In-stock
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Customer Review

Based on 2 publication(s) in Google Scholar

Other Forms of RS-127445 hydrochloride:

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2 Publications Citing Use of MCE RS-127445 hydrochloride

  • 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].

MedChemExpress (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].

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

Molecular Weight

317.79

Formula

C17H17ClFN3

CAS No.
Appearance

Solid

Color

Off-white to light yellow

SMILES

NC1=NC(C(C)C)=CC(C2=C3C=CC=CC3=C(F)C=C2)=N1.[H]Cl

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

Solvent & Solubility
In Vitro: 

DMSO : 125 mg/mL (393.34 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

H2O : < 0.1 mg/mL (insoluble)

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
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

  • Molarity Calculator

  • Dilution Calculator

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

Mass
=
Concentration
×
Volume
×
Molecular Weight *

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

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start)

C1

×
Volume (start)

V1

=
Concentration (final)

C2

×
Volume (final)

V2

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

  • Protocol 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

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

    Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
  • Protocol 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

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

    Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

g

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO +
+
%
Tween-80 +
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration: mg/mL
Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
 If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Purity & Documentation
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

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 3.1467 mL 15.7337 mL 31.4673 mL 78.6683 mL
5 mM 0.6293 mL 3.1467 mL 6.2935 mL 15.7337 mL
10 mM 0.3147 mL 1.5734 mL 3.1467 mL 7.8668 mL
15 mM 0.2098 mL 1.0489 mL 2.0978 mL 5.2446 mL
20 mM 0.1573 mL 0.7867 mL 1.5734 mL 3.9334 mL
25 mM 0.1259 mL 0.6293 mL 1.2587 mL 3.1467 mL
30 mM 0.1049 mL 0.5245 mL 1.0489 mL 2.6223 mL
40 mM 0.0787 mL 0.3933 mL 0.7867 mL 1.9667 mL
50 mM 0.0629 mL 0.3147 mL 0.6293 mL 1.5734 mL
60 mM 0.0524 mL 0.2622 mL 0.5245 mL 1.3111 mL
80 mM 0.0393 mL 0.1967 mL 0.3933 mL 0.9834 mL
100 mM 0.0315 mL 0.1573 mL 0.3147 mL 0.7867 mL
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  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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