Home Cart Sign in  
Chemical Structure| 135159-51-2 Chemical Structure| 135159-51-2

Structure of Sarpogrelate HCl
CAS No.: 135159-51-2

Chemical Structure| 135159-51-2

*Storage: {[sel_prStorage]}

*Shipping: {[sel_prShipping]}

,{[proInfo.pro_purity]}

Sarpogrelate HCl is an antagonist of both 5HT2A and 5-HT2B receptors, which can block serotonin-induced platelet aggregation and treat diabetes mellitus, Buerger's disease, Raynaud's disease, coronary artery disease, angina pectoris and atherosclerosis.

Synonyms: MCI-9042; Sarpogrelate (hydrochloride); Sarpogrelate hydrochloride

4.5 *For Research Use Only !

{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]} Purity: {[proInfo.pro_purity]}

Change View

Size Price VIP Price

DE Stock

US Stock

Asia Stock

Global Stock

In Stock
{[ item.pr_size ]} Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]}

  • {[ item.pr_size ]}

In Stock

- +

Please Login or Create an Account to: See VIP prices and availability

  • 1-2 Day Shipping
  • High Quality
  • Technical Support
Product Citations

Product Citations      Show More

Zhang, Yuxin ; Wang, Yizhou ; Zhang, Kun ; Liang, Xiurui ; Guan, Jing ; Jin, Jiaqi , et al.

Abstract: Previously, we found that the 5-HT2A receptor plays a key role in cell injury. However, the mechanism by which the 5-HT2A receptor mediates intracellular processes remains unclear. In this study, we aimed to clarify this intracellular process in hepatocyte LO2 cells and evaluate its role in CCl4-induced hepatotoxicity in mice. In vitro, both the agonist and overexpression of 5-HT2A receptor could promote 5-HT degradation by upregulating the expression of 5-HT synthases and monoamine oxidase-A (MAO-A) to cause overproduction of ROS in mitochondria. We refer to this as the activation of the 5-HT degradation system (5DS) axis, which leads to the phosphorylation of JNK, p38 MAPK, STAT3, and NF-κB; upregulation of Bax, cleaved-caspase3, and cleaved-caspase9; and downregulation of Bcl-2, followed by apoptosis and oversecretion of TNF-α and IL-1β in cells. This phenomenon could be markedly blocked by the 5-HT2A receptor antagonist, MAO-A inhibitor, or gene-silencing MAO-A. Through protein kinases C epsilon (PKCε) agonist treatment and gene silencing of the PKCε and 5-HT2A receptor, we demonstrated that the 5-HT2A receptor controls 5-HT synthases and MAO-A expression via the PKCε pathway in cells. Unexpectedly, we discovered that PKCε-mediated phosphorylation of the AKT/mTOR pathway is also a consequence of the activation of the 5DS axis. Furthermore, we confirmed that the inhibition of the 5DS axis using the 5-HT2A receptor antagonist could prevent hepatotoxicity induced by CCl4 both in vitro and in vivo, inhibiting the aforementioned signaling cascades, inflammation, and apoptosis, and that the 5DS activation area overlapped the necrotic area of mouse liver. Taken together, we revealed a 5DS axis in hepatocytes that controls the signaling cascades associated with inflammation and apoptosis and confirmed its role in CCl4-induced hepatotoxicity.

Keywords: 5-HT2A receptor ; Protein kinase C epsilon ; 5-HT degradation ; Reactive oxygen species ; Signaling cascade ; Cell injury

Purchased from AmBeed: ; 28860-95-9

Zhang, Yuxin ; Liang, Xiurui ; Guan, Jing ; Jin, Jiaqi ; Zhang, Yi ; Xu, Fan , et al.

Abstract: Previously we found that acute liver injury (ALI) with inflammation caused by carbon tetrachloride (CCl4) was associated with the activation of the 5-HT degradation system (5DS), which includes monoamine oxidase A (MAO-A), the 5-HT2A receptor, and 5-HT synthases in hepatocytes. This study aimed to determine the role of 5DS in mitochondrial damage and apoptosis. In hepatocyte LO2 cells, CCl4 activated 5-HT2A receptor at the gene level, and then 5-HT2A receptor mediated the expression of 5-HT synthase and MAO-A at the gene level. Suppression of 5DS with the 5-HT2A receptor antagonist, MAO-A inhibitor, or gene silencing MAO-A significantly reduced the CCl4-induced production of mitochondrial reactive oxygen species (ROS). The ROS-associated upregulation of mitochondrial division proteins (FIS1 and DRP1); downregulation of mitochondrial fusion-associated protein 1, respiratory chain proteins (ND1 and CYTB), and ATP6; and decrease of ATP levels were reversed. Moreover, ROS-associated abnormal levels of caspase pathway-associated proteins (Bcl-2, Bax, cleaved-caspase3 and cleaved-caspase9) and apoptosis were suppressed. Notably, a combination of 5-HT2A receptor antagonist and MAO-A inhibitor almost abolished CCl4 cytotoxicity; abolished mitochondrial membrane potential (MMP) depolarization, mitochondrial structural abnormality, and high mitochondrial pH, with low pH states of the nucleus and cytoplasm. The effects of both were more significant than either alone. LO2 cells exposed to H2O2 or depleted mitochondrial ROS showed that ROS induced mitochondrial division and apoptosis and inhibited the levels of respiratory chain proteins. CCl4-induced abnormalities of ATP generation and MMP were dependent on both ROS and other 5DS-associated factors, probably NH3. Investigation of CCl4-induced ALI mice showed that hepatic injury and apoptosis occur at the site of 5DS activation and are significantly inhibited by the 5-HT2A receptor antagonist and 5-HT synthetic inhibitor in a synergistic manner, as well as mitochondrial damage. Together, we revealed the close relationship between CCl4-induced activation of 5DS and mitochondrial damage, abnormal intracellular [H+], and apoptosis in hepatocytes.

Keywords: 5-HT degradation system ; Reactive oxygen species ; Mitochondrial division ; Mitochondrial respiratory chain ; Intracellular pH value ; Apoptosis

Purchased from AmBeed: ; 28860-95-9

Alternative Products

Product Details of Sarpogrelate HCl

CAS No. :135159-51-2
Formula : C24H32ClNO6
M.W : 465.97
SMILES Code : O=C(OC(COC1=CC=CC=C1CCC2=CC=CC(OC)=C2)CN(C)C)CCC(O)=O.[H]Cl
Synonyms :
MCI-9042; Sarpogrelate (hydrochloride); Sarpogrelate hydrochloride
MDL No. :MFCD00887582
InChI Key :POQBIDFFYCYHOB-UHFFFAOYSA-N
Pubchem ID :444005

Safety of Sarpogrelate HCl

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H302-H319-H332-H372-H400
Precautionary Statements:P260-P264-P270-P273-P280-P301+P312+P330-P304+P312-P305+P351+P338-P314-P337+P313-P391-P501
Class:9
UN#:3077
Packing Group:

Related Pathways of Sarpogrelate HCl

GPCR

Isoform Comparison

Biological Activity

Target
  • 5-HT2

    5-HT2C, Kd:1.1 nM

    5-HT2A, Kd:2.1 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
MDCK-II-BCRP cells 0.2, 1, 10 µM 1 hour Evaluate the inhibitory effects of Sarpogrelate and M-1 on BCRP-mediated prazosin transport, showing no significant inhibition Drug Des Devel Ther. 2016 Sep 14;10:2959-2972
MDCK-II-P-gp cells 0.2, 1, 10 µM 1 hour Evaluate the inhibitory effects of Sarpogrelate and M-1 on P-gp-mediated loperamide transport, showing <10% inhibition Drug Des Devel Ther. 2016 Sep 14;10:2959-2972
Cardiomyocytes 1 µM 48 hours Suppressed cardiomyocyte hypertrophy induced by PE, Ang II, and ET-1 Pharmaceuticals (Basel). 2021 Dec 5;14(12):1268

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Albino BALBc/J mice Light-induced retinopathy model Intraperitoneal injection 25 mg/kg Single dose, lasting 1 hour To investigate the neuroprotective effects and mechanisms of Sarpogrelate in a light-induced retinopathy model. Results showed that Sarpogrelate exerts neuroprotection through transient activation of the MAPK/ERK pathway and sustained activation of CREB, leading to transcription of anti-apoptotic genes Bcl2, Xiap, and Ucp3. Invest Ophthalmol Vis Sci. 2018 Jan 1;59(1):462-471
C57BL/6J male mice Transverse aortic constriction (TAC) surgery-induced heart failure model Oral 5 mg/kg Once daily for 8 weeks Suppressed TAC-induced cardiac hypertrophy and systolic dysfunction Pharmaceuticals (Basel). 2021 Dec 5;14(12):1268
New Zealand white rabbits High cholesterol diet-induced atherosclerosis model Oral 5 mg/kg/day Once daily for 90 days To investigate the effects of SP on high cholesterol diet-induced atherosclerosis. Results showed that SP reduced plasma cholesterol and triglyceride levels, decreased oxidative stress and blood viscosity, and inhibited the formation of atherosclerotic plaques. J Cell Mol Med. 2012 Oct;16(10):2394-400
BALB/c mice Light-induced retinopathy model Intraperitoneal injection 5, 15, 30, 40, 50 mg/kg 48, 24, and 0 hours before and 24 and 48 hours after exposure To evaluate the protective effect of sarpogrelate on light-induced retinopathy. Results showed that a 50 mg/kg dose completely protected retinal morphology and function. Invest Ophthalmol Vis Sci. 2015 Jul;56(8):4560-9

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT00147303 Cerebral Infarction PHASE3 COMPLETED 2025-01-05 -

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.15mL

0.43mL

0.21mL

10.73mL

2.15mL

1.07mL

21.46mL

4.29mL

2.15mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2
The prepared working fluid is recommended to be prepared now and used up as soon as possible in a short period of time. The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1

References

 

Historical Records

Categories