Effect of TRPV1 Antagonist SC0030, a Potent Painkiller, on RANKL‐mediated Osteoclast Differentiation Involved in Bone Resorption

More, Kunal N.; Lee, Yong‐Jin; Kim, Kwang‐Jin; Suh, Young‐Ger; Son, Young–Jin; Chang, Daesung

doi:10.1002/bkcs.11992

Cited by 4 publications

(2 citation statements)

References 27 publications

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“…TRPV1 activation leads to osteoclasts differentiation in the RANKL-mediated pathway. TRPV1 antagonist, SC0030, inhibited this process in vitro [314]. Considering this, dual CB2 agonists and TRPV1 antagonists are proposed as a promising tool in bone mass loss treatment [44].…”

Section: Osteologymentioning

confidence: 94%

A Guide to Targeting the Endocannabinoid System in Drug Design

Stasiulewicz

Znajdek

Grudzień

et al. 2020

IJMS

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The endocannabinoid system (ECS) is one of the most crucial systems in the human organism, exhibiting multi-purpose regulatory character. It is engaged in a vast array of physiological processes, including nociception, mood regulation, cognitive functions, neurogenesis and neuroprotection, appetite, lipid metabolism, as well as cell growth and proliferation. Thus, ECS proteins, including cannabinoid receptors and their endogenous ligands’ synthesizing and degrading enzymes, are promising therapeutic targets. Their modulation has been employed in or extensively studied as a treatment of multiple diseases. However, due to a complex nature of ECS and its crosstalk with other biological systems, the development of novel drugs turned out to be a challenging task. In this review, we summarize potential therapeutic applications for ECS-targeting drugs, especially focusing on promising synthetic compounds and preclinical studies. We put emphasis on modulation of specific proteins of ECS in different pathophysiological areas. In addition, we stress possible difficulties and risks and highlight proposed solutions. By presenting this review, we point out information pivotal in the spotlight of ECS-targeting drug design, as well as provide an overview of the current state of knowledge on ECS-related pharmacodynamics and show possible directions for needed research.

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Section: Osteologymentioning

confidence: 94%

A Guide to Targeting the Endocannabinoid System in Drug Design

Stasiulewicz

Znajdek

Grudzień

et al. 2020

IJMS

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“…By searching the small molecule database PubChem ( https://pubchem.ncbi.nlm.nih.gov/ ), TCMSP ( http://tcmspw.com/tcmsp.php ), TCMID ( http://www.Megabionet.org/tcmid/ ) and relevant literature, we found 60 components in CF ( Supplementary Table S1 ). And then, we searched for 10 TRPV1 agonists and 10 TRPV1 antagonists from the literature ( Supplementary Table S2 ) and downloaded small molecule ligands ( Gavva, 2008 ; Gunthorpe and Szallasi, 2008 ; Burgess and Williams, 2010 ; Li et al, 2011 ; Szolcsányi and Sándor, 2012 ; Sugimoto et al, 2013 ; Yin, 2019 ; Choi et al, 2020 ; Duarte et al, 2020 ; Mazeto et al, 2020 ; More et al, 2020 ; Nie, 2020 ). We also had to randomly download 90 compounds from the PubChem database that did not have well-defined TRPV1 agonist activity for later verification.…”

Section: Methodsmentioning

confidence: 99%

Integrated virtual screening and in vitro studies for exploring the mechanism of triterpenoids in Chebulae Fructus alleviating mesaconitine-induced cardiotoxicity via TRPV1 channel

Song,

Mi,

Zhao

et al. 2024

Front. Pharmacol.

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Background: In traditional Mongolian or Tibetan medicine in China, Chebulae Fructus (CF) is widely used to process or combine with aconitums to decrease the severe toxicity of aconitums. Researches in this area have predominantly focused on tannins, with few research on other major CF components for cardiotoxicity mitigation. The present study aimed to clarify whether triterpenoids can attenuate the cardiotoxicity caused by mesaconitine (MA) and investigate the mechanism of cardiotoxicity attenuation.Methods: Firstly, the pharmacophore model, molecular docking, and 3D-QSAR model were used to explore the mechanism of CF components in reducing the toxicity of MA mediated by the TRPV1 channel. Then three triterpenoids were selected to verify whether the triterpenoids had the effect of lowering the cardiotoxicity of MA using H9c2 cells combined with MTT, Hoechst 33258, and JC-1. Finally, Western blot, Fluo-3AM, and MTT assays combined with capsazepine were used to verify whether the triterpenoids reduced H9c2 cardiomyocyte toxicity induced by MA was related to the TRPV1 channel.Results: Seven triterpenoids in CF have the potential to activate the TRPV1 channel. And they exhibited greater affinity for TRPV1 compared to other compounds and MA. However, their activity was relatively lower than that of MA. Cell experiments revealed that MA significantly reduced H9c2 cell viability, resulting in diminished mitochondrial membrane potential and nuclear pyknosis and damage. In contrast, the triterpenoids could improve the survival rate significantly and counteract the damage of MA to the cells. We found that MA, arjungenin (AR), and maslinic acid (MSA) except corosolic acid (CRA) upregulated the expression of TRPV1 protein. MA induced a significant influx of calcium, whereas all three triterpenoids alleviated this trend. Blocking the TRPV1 channel with capsazepine only increased the cell viability that had been simultaneously treated with MA, and AR, or MSA. However, there was no significant difference in the CRA groups treated with or without capsazepine.Conclusion: The triterpenoids in CF can reduce the cardiotoxicity caused by MA. The MSA and AR function as TRPV1 agonists with comparatively reduced activity but a greater capacity to bind to TRPV1 receptors, thus antagonizing the excessive activation of TRPV1 by MA.

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Research progress and challenges of TRPV1 channel modulators as a prospective therapy for diabetic neuropathic pain

Liu

Miao

Raza

et al. 2023

European Journal of Medicinal Chemistry

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Effect of TRPV1 Antagonist SC0030, a Potent Painkiller, on RANKL‐mediated Osteoclast Differentiation Involved in Bone Resorption

Abstract: Potent TRPV1 inhibitor SC0030 was evaluated for inhibitory effect on osteoclast differentiation, a main process involved in pathology of osteoporosis. Osteoclast differentiation inhibitory study suggested that TRPV1 inhibitor SC0030 would be beneficial for prevention.

Cited by 4 publications

References 27 publications

A Guide to Targeting the Endocannabinoid System in Drug Design

A Guide to Targeting the Endocannabinoid System in Drug Design

Integrated virtual screening and in vitro studies for exploring the mechanism of triterpenoids in Chebulae Fructus alleviating mesaconitine-induced cardiotoxicity via TRPV1 channel

Research progress and challenges of TRPV1 channel modulators as a prospective therapy for diabetic neuropathic pain

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