Famotidine inhibits glycogen synthase kinase-3β: An investigation by docking simulation and experimental validation

Mohammad, Mohammad; Almasri, Ihab M.; Issa, Ala; Al-Ghussein, Mohamed A. S.; Fararjeh, Mohammad; AlKhatib, Hatim S.; Taha, Mutasem O.; Bustanji, Yasser

doi:10.3109/14756366.2012.672413

Cited by 7 publications

(5 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…GSK‐3 β crystal structure with PDB: 1Q5 K consists of two chains A and B with the sequence length of 414. The binding pocket was defined from the crystallographic structure of AR‐A014418, which is a known GSK‐3 β ligand with high affinity [66] . The main residues in this pocket were ILE‐62, ALA‐83, ASP‐133, VAL‐135**, ARG‐141 and LEU‐188.…”

Section: Resultsmentioning

confidence: 99%

“…The binding pocket was defined from the crystallographic structure of AR-A014418, which is a known GSK-3β ligand with high affinity. [66] The main residues in this pocket were ILE-62, ALA-83, ASP-133, VAL-135**, ARG-141 and LEU-188. Molecular docking of triolein, trilinolein, trimyristin, oleic acid, linoleic acid, myristic acid and AR-A014418 inhibitor within the binding pocket of GSK-3β was performed.…”

Section: Molecular Docking Studymentioning

confidence: 97%

See 1 more Smart Citation

Chemical Profile of the Pits Oil from the Tunisian ‘Alig’ Cultivar ofPhoenix dactyliferaL.:In VivoWound Healing Potential Evaluation of a Cream Formulated from the Extracted Oil and Insights from Molecular Docking and SAR Analysis

Chhoud

Bagga

Lassoued

et al. 2022

Chemistry & Biodiversity

View full text Add to dashboard Cite

Since ancient times the oil from date palm pits (Phoenix dactylifera L.) has been used to heal wounds. In order to prove this traditional usage of the pits, this oil was extracted from the pits of the Tunisian cultivar 'Alig' and its physico-chemical properties and the chemical composition were evaluated. The fatty acid profile, evidenced by GC, allowed to classify this oil as an oleic-myristic acid oil with a clear abundance of oleic acid (53.66 %). 1 H and 13 C-NMR as well as FT-IR analyses confirmed the presence of fatty acids in triglyceride forms. Furthermore, in vivo wound healing activity of a cream formulated from the extracted oil was performed, for the first time, using a rat model and was compared to placebo cream and a commercial formulation, MEBO®. This study showed that the test cream promoted the healing of pressure ulcers better than the placebo cream and the MEBO® ointment. The results showed that this vegetable oil is able to improve the healing of infected wounds in rats, thus supporting its traditional use. The contribution of the main oleic, linoleic and myristic acids that can be derived from enzymatic hydrolysis to the healing activity of the whole pits oil was predicted by in silico study and the calculated pharmacokinetics parameters.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Molecular Docking Studymentioning

confidence: 97%

Chemical Profile of the Pits Oil from the Tunisian ‘Alig’ Cultivar ofPhoenix dactyliferaL.:In VivoWound Healing Potential Evaluation of a Cream Formulated from the Extracted Oil and Insights from Molecular Docking and SAR Analysis

Chhoud

Bagga

Lassoued

et al. 2022

Chemistry & Biodiversity

View full text Add to dashboard Cite

show abstract

“…Despite the different kinase inhibitory properties of the investigated drugs, they have all been shown to have the ability to also inhibit GSK3. This was demonstrated in separate invitro studies [23][24][25][26][27][28]. Famotidine is a competitive inhibitor of the histamine (H2) receptor, the dominant receptor involved in gastric acid secretion that abolishes the activation of adenylate cyclase induced by histamines.…”

Section: Kinase Inhibitory Properties Of Investigated Drugsmentioning

confidence: 91%

“…Famotidine and Olanzapine have been investigated for their potential to inhibit GSK3 due to their hypoglycemic side effects. Docking and experimental studies have demonstrated that Famotidine is fit within the binding pocket of GSK-3β and can decrease the glycemic response curve in animals [23][24][25].…”

Section: Kinase Inhibitory Properties Of Investigated Drugsmentioning

confidence: 99%

“…Table 1 lists the drugs used in this study, their mode of action and current applications. Separate in vitro studies have demonstrated these drugs to have hypoglycemic side effects and subsequent studies have shown their ability to inhibit GSK3 [23][24][25][26][27][28]. Therefore, we reasoned we could exhibit their potential to stimulate Wnt signaling pathway in the dental pulp cells.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Drug Repurposing in Dentistry: Towards Application of Small Molecules in Dentin Repair

Birjandi

Suzano

Sharpe

2020

IJMS

View full text Add to dashboard Cite

One of the main goals of dentistry is the natural preservation of the tooth structure following damage. This is particularly implicated in deep dental cavities affecting dentin and pulp, where odontoblast survival is jeopardized. This activates pulp stem cells and differentiation of new odontoblast-like cells, accompanied by increased Wnt signaling. Our group has shown that delivery of small molecule inhibitors of GSK3 stimulates Wnt/β-catenin signaling in the tooth cavity with pulp exposure and results in effective promotion of dentin repair. Small molecules are a good therapeutic option due to their ability to pass across cell membranes and reach target. Here, we investigate a range of non-GSK3 target small molecules that are currently used for treatment of various medical conditions based on other kinase inhibitory properties. We analyzed the ability of these drugs to stimulate Wnt signaling activity by off-target inhibition of GSK3. Our results show that a c-Met inhibitor, has the ability to stimulate Wnt/β-catenin pathway in dental pulp cells in vitro at low concentrations. This work is an example of drug repurposing for dentistry and suggests a candidate drug to be tested in vivo for natural dentin repair. This approach bypasses the high level of economical and time investment that are usually required in novel drug discoveries.

show abstract

Phytochemicals from Nigerian medicinal plants modulate therapeutically-relevant diabetes targets: insight from computational direction

Olawale

Olofinsan

Iwaloye

et al. 2021

ADV TRADIT MED (ADTM)

View full text Add to dashboard Cite

Famotidine inhibits glycogen synthase kinase-3β: An investigation by docking simulation and experimental validation

Cited by 7 publications

References 13 publications

Chemical Profile of the Pits Oil from the Tunisian ‘Alig’ Cultivar ofPhoenix dactyliferaL.:In VivoWound Healing Potential Evaluation of a Cream Formulated from the Extracted Oil and Insights from Molecular Docking and SAR Analysis

Chemical Profile of the Pits Oil from the Tunisian ‘Alig’ Cultivar ofPhoenix dactyliferaL.:In VivoWound Healing Potential Evaluation of a Cream Formulated from the Extracted Oil and Insights from Molecular Docking and SAR Analysis

Drug Repurposing in Dentistry: Towards Application of Small Molecules in Dentin Repair

Phytochemicals from Nigerian medicinal plants modulate therapeutically-relevant diabetes targets: insight from computational direction

Contact Info

Product

Resources

About