Expert Opinion on Therapeutic Patents, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 25
Published: Dec. 31, 2024
Histamine H3 receptor antagonists/inverse agonists, since the discovery of histamine (H3R), are important ligands in search for new potential drugs. The most interesting CNS diseases as these receptors mainly there preseant.
Language: Английский
Biomedicine & Pharmacotherapy, Journal Year: 2025, Volume and Issue: 183, P. 117850 - 117850
Published: Jan. 15, 2025
Language: Английский
Citations
0
ACS Pharmacology & Translational Science, Journal Year: 2025, Volume and Issue: 8(4), P. 951 - 977
Published: March 7, 2025
Cancer ranks among the top triumvirate leading causes of human deaths worldwide. The pathological mechanisms are notably intricate, demonstrating proliferative and metastatic capabilities, which complicate therapeutic interventions. sigma-1 receptor (σ1R) plays a crucial role in tumor survival migration, while sigma-2 (σ2R) is intimately associated with proliferation. This review encapsulated investigation concerning σ1R σ2R neoplasms rigorously summarized ligands radio-ligands development their applications, such as antitumor cell proliferation PET/SPECT imaging tumors. A comprehensive classification discussion was undertaken regarding chemical structures emphasized possibility dual/multitargeted ligands. Ultimately, we discussed effects chiral pharmacological characteristics on affinity pharmacokinetic features vivo, particularly radiopharmaceuticals. functions beneficial resource, fostering ligand deployment stimulating generation innovative ideas for developing
Language: Английский
Citations
0
Chemico-Biological Interactions, Journal Year: 2025, Volume and Issue: unknown, P. 111497 - 111497
Published: March 1, 2025
Language: Английский
Citations
0
Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 100, P. 102373 - 102373
Published: July 2, 2024
Language: Английский
Citations
2
Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(1), P. 121 - 121
Published: Jan. 17, 2024
This work relates to the design and synthesis of a series novel multi-target directed ligands (MTDLs), i.e., compounds 4a–l, via convenient one-pot three-component Hantzsch reaction. approach targeted calcium channel antagonism, antioxidant capacity, cathepsin S inhibition, interference with Nrf2 transcriptional activation. Of these MTDLs, 4i emerged as promising compound, demonstrating robust activity, ability activate Nrf2-ARE pathways, well blockade inhibition. Dihydropyridine represents first example an MTDL that combines biological activities.
Language: Английский
Citations
2
Pharmacological Reports, Journal Year: 2023, Volume and Issue: 75(5), P. 1291 - 1298
Published: Aug. 12, 2023
Although the terms "agonist" and "antagonist" have been used to classify sigma-1 receptor (σ1R) ligands, an unambiguous definition of functional activity is often hard. In order determine pharmacological profile σ1R most common method assess their potency alleviate opioid analgesia. It has well established that agonists reduce analgesic activity, while antagonists demonstrated enhance analgesia in different pain models. present study, we evaluated selected ligands using a novel object recognition (NOR) test, see if any differences cognitive functions between could be observed. We highly selective PRE-084 S1RA as reference agonist antagonist, respectively. Furthermore, compound KSK100 from our ligand library was also included this study. previously characterized dual-targeting histamine H3/σ1R antagonist with antinociceptive antiallodynic vivo. Donepezil (acetylcholinesterase inhibitor agonist) positive control drug. Both tested (donepezil PRE-084) improved learning NOR which not observed KSK100. The nonlinear dose-response effect assay does justify its use for routine assessment ligands.
Language: Английский
Citations
4
International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(15), P. 8035 - 8035
Published: July 23, 2024
The future of therapy for neurodegenerative diseases (NDs) relies on new strategies targeting multiple pharmacological pathways. Our research led to obtaining the compound AR71 [(E)-3-(3,4,5-trimethoxyphenyl)-1-(4-(3-(piperidin-1-yl)propoxy)phenyl)prop-2-en-1-one], which has high affinity human H
Language: Английский
Citations
1
Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: unknown
Published: July 16, 2024
Multitarget strategies are essential in addressing complex diseases, yet developing multitarget-directed ligands (MTDLs) is particularly challenging when aiming to engage multiple therapeutic targets across different tissues. Here, we present a molecular transformer strategy, enhancing traditional MTDLs. By utilizing esterase-driven hydrolysis, this approach mimics the adaptive nature of transformers for enabling molecules modify their pharmacological effects response biological milieu. virtual screening and evaluation, identified KGP-25, novel compound initially targeting voltage-gated sodium channel 1.8 (Nav1.8) peripheral nervous system (PNS) analgesia, later γ-aminobutyric acid subtype A receptor (GABAA) central (CNS) general anesthesia. Our findings confirm KGP-25's dual efficacy cellular animal models, effectively reducing opioid-related side effects. This study validates drug design highlights its potential overcome limitations conventional MTDLs, paving new avenues innovative strategies.
Language: Английский
Citations
0
RSC Medicinal Chemistry, Journal Year: 2024, Volume and Issue: unknown
Published: Jan. 1, 2024
Developing sigma-1 receptor (S1R) modulators is considered a valuable therapeutic strategy to counteract neurodegeneration, cancer progression, and viral infections, including COVID-19.
Language: Английский
Citations
0
ACS Chemical Neuroscience, Journal Year: 2024, Volume and Issue: unknown
Published: Dec. 9, 2024
In this study, we selected 12 guanidine derivatives from the previously described ligand library and determined their affinity at histamine H
Language: Английский
Citations
0