Preclinical In Vitro Studies: Development and Applicability

Osakwe, Odilia

doi:10.1016/b978-0-12-802220-7.00006-5

Cited by 8 publications

(3 citation statements)

References 65 publications

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“…Target validation is considered a process demonstrating the target that has been identified have a functional role in disease process. (4) It involves studies intact with animal models that can provide information about the organism response to pharmacological interventions. By this it will help to know whether the identified target is relevant to the disease that has been studied.…”

Section: Target Validationmentioning

confidence: 99%

A Systematic Review on Clinical Research and Approval Process

Nishabh,

N. Kshitija

2023

Asian J Pharm Res Dev

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Drug discovery is a key step or process by which lead molecule is been optimized for further preclinical and clinical trial studies. Drug development process involves target identification, target validation, lead identification, and lead optimization. Once the lead molecule is optimized the HIT compound is been analyzed further in preclinical trial in animals and clinical trial in human subjects. The development of a new drug till marketing authorization should gone through several stages in order to make the drug safe, effective and should posses best quality to get approve for applicable regulatory requirements. The overall theme of our article is to review and state the process from drug discovery to approval for marketing of drug. The process from drug discovery till marketing authorization is time taking, complex and expensive so each target should be consider for development of new drug and new research tools must be used for any new drug development process. It takes around 10-15 years and US$ 1 billion for a new lead compound to make it as a medicine and to get marketing approval for general public use. On an average million lead molecules are been scrutinized to make a HIT compound, so that it can be use for further preclinical and clinical studies to make it available in market. This article provides a brief outline on stages from drug development to clinical research.

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Section: Target Validationmentioning

confidence: 99%

A Systematic Review on Clinical Research and Approval Process

Nishabh,

N. Kshitija

2023

Asian J Pharm Res Dev

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“…After successful completion of preliminary in vitro studies, scaffolds are tested in vivo using animal models to analyse the response in real time and to verify their safety and efficacy. The use of in vitro and in vivo studies is crucial to avoid harm to people that the unknown graft could cause 158 .…”

Section: Preclinical and Clinical Studies On The Musculoskeletal Interface Regeneration 61 Preclinical Studiesmentioning

confidence: 99%

Current Advances on the Regeneration of Musculoskeletal Interfaces

Balestri

Morris

Hunt

et al. 2021

Tissue Engineering Part B: Reviews

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The regeneration of the musculoskeletal system has been widely investigated. There is now detailed knowledge about the organs composing this system. Research has also investigated the zones between individual tissues where physical, mechanical and biochemical properties transition. However, the understanding of the regeneration of musculoskeletal interfaces is still lacking behind. Numerous disorders and injuries can degrade or damage tissue interfaces. Their inability to regenerate can delay the repair and regeneration process of tissues, leading to graft instability, high morbidity and pain. Moreover, the knowledge of the mechanism of tissue interface development is not complete. This review presents an overview of the most recent approaches of the regeneration of musculoskeletal interfaces, describing the latest in vitro, preclinical and clinical studies.

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“…These brominated indoles effectively reduced cell viability and induced apoptosis in two human colon adenocarcinoma cell lines, HT29 and Caco2 [110], as well as induced apoptosis in DNA-damaged cells of the colon in vivo [109,111]. Caco-2 cells are most frequently used in intestinal permeability models, and they have been validated for drug absorption studies [112]. Notably, the COX-2 isoenzyme has been demonstrated to play a vital role in the progression of colorectal cancer through the elevation of angiogenesis, anti-apoptotic effects, and increased invasiveness [113].…”

Section: Pharmacokinetics and Toxicological Propertiesmentioning

confidence: 99%

Mollusc-Derived Brominated Indoles for the Selective Inhibition of Cyclooxygenase: A Computational Expedition

et al. 2021

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Inflammation plays an important role in different chronic diseases. Brominated indoles derived from the Australian marine mollusk Dicathais orbita (D. orbita) are of interest for their anti-inflammatory properties. This study evaluates the binding mechanism and potentiality of several brominated indoles (tyrindoxyl sulfate, tyrindoleninone, 6-bromoisatin, and 6,6′-dibromoindirubin) against inflammatory mediators cyclooxygenases-1/2 (COX-1/2) using molecular docking, followed by molecular dynamics simulation, along with physicochemical, drug-likeness, pharmacokinetic (pk), and toxicokinetic (tk) properties. Molecular docking identified that these indole compounds are anchored, with the main amino acid residues, positioned in the binding pocket of the COX-1/2, required for selective inhibition. Moreover, the molecular dynamics simulation based on root mean square deviation (RMSD), radius of gyration (Rg), solvent accessible surface area (SASA), and root mean square fluctuation (RMSF) analyses showed that these natural brominated molecules transit rapidly to a progressive constant configuration during binding with COX-1/2 and seem to accomplish a consistent dynamic behavior by maintaining conformational stability and compactness. The results were comparable to the Food and Drug Administration (FDA)-approved selective COX inhibitor, aspirin. Furthermore, the free energy of binding for the compounds assessed by molecular mechanics–Poisson–Boltzmann surface area (MM–PBSA) confirmed the binding capacity of indoles towards COX-1/2, with suitable binding energy values except for the polar precursor tyrindoxyl sulfate (with COX-1). The physicochemical and drug-likeness analysis showed zero violations of Lipinski’s rule, and the compounds are predicted to have excellent pharmacokinetic profiles. These indoles are projected to be non-mutagenic and free from hepatotoxicity, with no inhibition of human ether-a-go–go gene (hERG) I inhibitors, and the oral acute toxicity LD50 in rats is predicted to be similar or lower than aspirin. Overall, this work has identified a plausible mechanism for selective COX inhibition by natural marine indoles as potential therapeutic candidates for the mitigation of inflammation.

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Preclinical In Vitro Studies: Development and Applicability

Cited by 8 publications

References 65 publications

A Systematic Review on Clinical Research and Approval Process

A Systematic Review on Clinical Research and Approval Process

Current Advances on the Regeneration of Musculoskeletal Interfaces

Mollusc-Derived Brominated Indoles for the Selective Inhibition of Cyclooxygenase: A Computational Expedition

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