RS-127445 hydrochloride

Name: RS-127445 hydrochloride
Brand: MedChemExpress
SKU: HY-15419
Rating: 4.5 (2 reviews)

Cat. No.: HY-15419 Purity: 99.58%: FAQs
Data Sheet SDS COA Handling Instructions

RS-127445 hydrochloride is a selective, high affinity, orally bioavailable 5-HT_2B receptor antagonist with a pK_i 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

CAS No. : 199864-86-3

Size	Price	Stock	Quantity
Solid + Solvent
10 mM * 1 mL in DMSO ready for reconstitution	USD 73	In-stock	Estimated Time of Arrival: December 31
Solution
10 mM * 1 mL in DMSO	USD 73	In-stock	Estimated Time of Arrival: December 31
Solid
5 mg	USD 66	In-stock	Estimated Time of Arrival: December 31
10 mg	USD 106	In-stock	Estimated Time of Arrival: December 31
50 mg	USD 422	In-stock	Estimated Time of Arrival: December 31
100 mg		Get quote
200 mg		Get quote

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Customer Review

Based on 2 publication(s) in Google Scholar

Other Forms of RS-127445 hydrochloride:

RS-127445 Get quote

2 Publications Citing Use of MCE RS-127445 hydrochloride

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•Related Screening Libraries:

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View All 5-HT Receptor Isoform Specific Products:

View All Isoforms

5-HT₁ Receptor 5-HT₂ Receptor 5-HT₃ Receptor 5-HT₄ Receptor 5-HT₅ Receptor 5-HT₆ Receptor 5-HT₇ Receptor 5-HT Receptor

Biological Activity
Protocol
Purity & Documentation
References
Customer Review

Description

IC₅₀ & Target

sPLA2

5.5 (pKi)

5-HT₃ Receptor

<6 (pKi)

5-HT₅ Receptor

<6 (pKi)

5-HT₆ Receptor

<6 (pKi)

5-HT_2A Receptor

6.3 (pKi)

5-HT_2C Receptor

6.4 (pKi)

5-HT_2B Receptor

9.5 (pKi)

In Vitro

RS-127445 is found to has nanomolar affinity for the 5-HT_2B receptor (pK_i=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-HT_2B receptors expressed in CHO-K1 cells. The affinity (pK_i value) of RS-127445 for the 5-HT_2B receptor is 9.5±0.1 (n=9). RS-127445 is selective for the 5-HT_2B receptor, having approximately 1000 fold lower affinity for the human recombinant 5-HT_2A, 5-HT_2C, 5-HT₅, 5-HT₆ and 5-HT₇ receptors, a 5-HT_1A receptor in rat brain membranes, a 5-HT_1B/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-HT_2B receptor (pIC₅₀ of 10.4±0.1). In cells expressing human recombinant 5-HT_2B receptors, RS-127445 potently antagonizes 5-HT-evoked formation of inositol phosphates (pK_B=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 (pA_2B=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-HT_2B 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

Appearance

Solid

Formula

C₁₇H₁₇ClFN₃

CAS No.

199864-86-3

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 : ≥ 31 mg/mL (97.55 mM)

H₂O : < 0.1 mg/mL (insoluble)

*"≥" 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 available by MedChemExpress (MCE).

Purity & Documentation

Purity: 99.58%

Select Batch:

Data Sheet (282 KB) SDS (420 KB)

COA (249 KB) LCMS (98 KB)

Handling Instructions (2659 KB)

References

[1]. Bonhaus DW, et al. RS-127445: a selective, high affinity, orally bioavailable 5-HT2B receptor antagonist. Br J Pharmacol. 1999 Jul;127(5):1075-82. [Content Brief]

[2]. Bassil AK, et al. Inhibition of colonic motility and defecation by RS-127445 suggests an involvement of the 5-HT2B receptor in rodent large bowel physiology. Br J Pharmacol. 2009 Sep;158(1):252-8 [Content Brief]

Cell Assay ^[1]	HEK-293 cells expressing the human 5-HT_2B 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	[1]. Bonhaus DW, et al. RS-127445: a selective, high affinity, orally bioavailable 5-HT2B receptor antagonist. Br J Pharmacol. 1999 Jul;127(5):1075-82. [Content Brief] [2]. Bassil AK, et al. Inhibition of colonic motility and defecation by RS-127445 suggests an involvement of the 5-HT2B receptor in rodent large bowel physiology. Br J Pharmacol. 2009 Sep;158(1):252-8 [Content Brief]