Cat. No.: HY-187979

RS67506 free base

RS67506 free base is a 5-HT₄ receptor partial agonist. RS67506 free base activates Gs-coupled signaling, increases cAMP/PKA and CREB phosphorylation/nuclear translocation, and promotes enteric neuron survival, neurogenesis, and GFAP -positive glial cell proliferation. RS67506 free base can be used for research on enteric neuropathy and constipation.

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

CAS No.: 160845-97-6
Formula: C₁₈H₂₈ClN₃O₄S
Molecular Weight:417.95

Storage:

Please store the product under the recommended conditions in the Certificate of Analysis.

Data Sheet (288 KB)

RS67506 free base Chemical Structure

CAS No.: 160845-97-6

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Use of MCE Products

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biological Activity
- Description
- IC₅₀ & Target
- In Vitro
- In Vivo
Chemical Information
Purity & Documentation
References
Calculators
Help & FAQs
Classifications
Bioz

Biological Activity

Description

IC₅₀ & Target

^[1]^[2]^[3]^[4]^[5]^[6]^[7]

5-HT₄ Receptor

PKA

cAMP

CREB

All 5-HT Receptor Isoforms :

All PKA Isoforms :

In Vitro

ApoptosisCell Cycle RegulationOthers

Apoptosis

RS67506 (10 nM) free base reduces TUNEL-positive apoptosis in fetal rat p75NTR-immunoselected enteric cultures in a 5-HT₄-dependent manner^[1].
RS67506 (10 nM) free base reduces TUNEL-positive apoptosis in adult mouse enteric neurons, an effect blocked by 5-HT₄ antagonism^[1].

Apoptosis

Cell Cycle Regulation

RS67506 (100 nM, 7 days) free base increases neuronal density, Tuj1+ EdU incorporation, and glial proliferation without increasing glial density or apoptosis in cultured mouse colon neurosphere-like body-derived intestinal progenitor cells^[3].

Cell Cycle Regulation

RS67506 (550 nM; 7 days) free base increases neuronal differentiation to 34.9% Tuj1+ cells and neurite length to 435.3 μm in postnatal mouse ENSC cultures^[6].

Others

RS67506 (0.1-100 nM; 48 h) free base concentration-dependently promotes the development/survival of β3-tubulin-positive neurons and neurite extension in E12-E13 mouse p75NTR-immunoselected gut crest-derived cultures, with the survival/differentiation effects disappearing at high concentrations, and is blocked by GR 113808 (HY-103152)^[1].
RS67506 (0.1-10 nM; 20 min) free base increases CREB phosphorylation and nuclear pCREB in adult mouse enteric neurons through 5-HT₄ and PKA-sensitive signaling pathways^[1].
RS67506 (60 min) free base is a high-affinity 5-HT₄ ligand (pK_i 8.8) in guinea pig striatal membranes, with significant σ1/σ2 binding (pK_i 7.9/7.3) and lower affinity for other tested receptors^[4].
RS67506 free base is a potent partial 5-HT₄ receptor agonist in the rat isolated esophageal muscularis mucosae (pEC₅₀ 8.8; 0.6 relative to 5-HT)^[4].
RS67506 (30 min) free base is a partial agonist of the 5-HT₄ receptor in the rat esophageal muscularis mucosae, with a pEC₅₀ of 7.5 and an intrinsic activity of 0.6 relative to 5-HT^[7].
RS67506 free base binds to guinea pig striatal 5-HT₄ receptors with a pKi of 8.8 and to NG108-15 cell 5-HT₃ receptors with a pKi of 5.6^[7].

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

Immunofluorescence^[1]

Cell Line:

β3-tubulin-positive neuronal
Concentration:

0.1; 1; 10; 100 nM
Incubation Time:

48 h
Result:

Promoted neuronal development/survival and neurite outgrowth in a concentration-dependent manner.
This effect was blocked by GR 113808 (HY-103152).

Immunofluorescence^[1]

Cell Line:

Adult mouse enteric neurons
Concentration:

0.1; 10 nM
Incubation Time:

20 min
Result:

Increased CREB phosphorylation and intranuclear pCREB.

In Vivo

Cardiovascular RegulationCell Cycle RegulationOthers

Cardiovascular Regulation

RS67506 (0.3-300 μg/kg; intravenous bolus; escalating sequential dosing with 10-minute intervals between doses) free base produces dose-dependent tachycardia in anesthetized miniature pigs, with an ED₅₀ of 5.4 μg/kg and a maximum heart rate increase of 47 beats/min^[4].

Cell Cycle Regulation

RS67506 (11.4 fmol/d-100 nM; intraperitoneal osmotic pump infusion for 7 days; BrdU (5-BrdU) (HY-15910) administered subsequently in drinking water) free base promotes 5-HT₄-dependent BrdU incorporation into enteric neural precursor cells and newly generated HuC/D-positive neurons in adult WT mice, with cells appearing in the extraganglionic germinal microenvironment and migrating toward the myenteric ganglia^[1].

Others

RS67506 (5 μmol dissolved in 200 μL saline; injected intraluminally into the proximal colon via a manometry catheter; single administration) free base stimulates colonic phase III-like contractions and fecal output in conscious healthy rats, and intravenous administration of creosote prevents its distal colonic motor effects^[5].

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

Animal Model:

SvEv129 (male, at least 6 weeks old)^[1]
Dosage:

11.4 fmol/d (intraperitoneal osmotic pump); 100 nM (drinking water)
Administration:

intraperitoneal continuous osmotic pump infusion for 7 days; oral drinking water during post-BrdU chase
Result:

Continuous BrdU produced BrdU-labeled extraganglionic cells with punctate HuC/D immunoreactivity in WT small and large intestine after 2-4 weeks of chase.
Virtually no BrdU/HuC/D coexpression was seen.
After 4 weeks, BrdU-labeled cells coexpressed DCX, Sox10, Phox2b, or nestin, and a subset coexpressed Musashi-1.
Rare cells showed perinuclear HuC/D.
HuC/D/BrdU cells were extraganglionic at 4 weeks and closely apposed to myenteric ganglia by 16 weeks.
In-cell ELISA showed increased BrdU incorporation in WT LMMP after 4 weeks relative to vehicle.

Animal Model:

Yucatan micropig (male and female; 17-22 kg)^[4]
Dosage:

0.3-300 μg/kg
Administration:

i.v. bolus; ascending series; 10 minutes between doses
Result:

Produced dose-dependent increases in heart rate.
ED₅₀ was 5.4 μg/kg i.v.
The maximum heart rate increase was 47 beats/min.

Animal Model:

Wistar Hannover GALAS (male, 200-250 g)^[5]
Dosage:

5 μmol in 200 μL saline
Administration:

intraluminal into the proximal colon via the manometric catheter; single administration
Result:

Intraluminal administration increased the frequency of phase III-like contractions and %MI in both the proximal and distal colon and increased the number of excreted fecal pellets.
In the distal colon, i.v. wood creosote 5 μg prevented the increases in phase III-like contraction frequency and %MI; in the proximal colon, the increases were not altered.
I.v. wood creosote 5 μg also prevented the increase in fecal pellet output.

Related Protocols :

Chemical Information

CAS No. 160845-97-6
Molecular Weight 417.95
Formula C₁₈H₂₈ClN₃O₄S
SMILES

O=C(CCC1CCN(CC1)CCNS(=O)(C)=O)C2=CC(Cl)=C(C=C2OC)N
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

Purity & Documentation

Select Batch:

Purity: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (288 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

References

[1]. Liu MT, et al. 5-HT4 receptor-mediated neuroprotection and neurogenesis in the enteric nervous system of adult mice. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2009 Aug 05;29(31):9683-99.

[2]. Cartolano MC, et al. Pulsatile urea excretion in Gulf toadfish: the role of circulating serotonin and additional 5-HT receptor subtypes. Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology. 2019 Oct;189(5):537-548.

[3]. Belkind-Gerson J, et al. Colitis induces enteric neurogenesis through a 5-HT4-dependent mechanism. Inflammatory bowel diseases. 2015 Apr;21(4):870-8.

[4]. Eglen RM, et al. Pharmacological characterization of two novel and potent 5-HT4 receptor agonists, RS 67333 and RS 67506, in vitro and in vivo. British journal of pharmacology. 1995 Aug;115(8):1387-92. [Content Brief]

[5]. Ataka K, et al. Wood creosote prevents CRF-induced motility via 5-HT3 receptors in proximal and 5-HT4 receptors in distal colon in rats. Autonomic neuroscience : basic & clinical. 2007 May 30;133(2):136-45.

[6]. Hotta R, et al. Delivery of enteric neural progenitors with 5-HT4 agonist-loaded nanoparticles and thermosensitive hydrogel enhances cell proliferation and differentiation following transplantation in vivo. Biomaterials. 2016 May;88:1-11.

[7]. Nagakura Y, et al. The selective 5-hydroxytryptamine (5-HT)4-receptor agonist RS67506 enhances lower intestinal propulsion in mice. Japanese journal of pharmacology. 1997 Jun;74(2):209-12.

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Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

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RS67506 free base

All 5-HT Receptor Isoforms

All PKA Isoforms