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Drug Development - Europe PMC

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Last Updated: 13 June 2022

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Development of applicable thiol-linked antibody-drug conjugates with improved stability and therapeutic index.

"Maleimides are normally used for coupling with antibody-reactive thiol moieties of antibodies in antibody-drug conjugates by the thiol moieties of antibodies in antibody-drug conjugates by the thiol-Michael click chemistry. " Meanwhile, a series of linkers based on maleamic methyl ester were used to conjugate the popular monomethyl auristatin E to an anti-HER2 antibody, increasing the stability and eliminating the need to alter the basic structure of traditional ADCs' ideal stable metabolite. Our preferred ADC mil40-12b not only has greater longevity than traditional ADCs, but also has improved safety data in mice," according to In vivo studies.

Source link: https://europepmc.org/article/MED/35244495


Metabolism and Excretion of Nirmatrelvir in Humans Using Quantitative Fluorine NMR Spectroscopy: A Novel Approach For Accelerating Drug Development.

"With a novel use of quantitative fluorine NMR spectroscopy in place of a standard radiolabel ADME study, we were able to assess the metabolism and excretion of unlabeled nirmatrelvir within the first-in-human study. " Six healthy subjects were given a single 300-mg oral dose of nirmatrelvir and excreta were collected up to ten days. The excretion of fluorine-containing substances in urine and feces was 47. 0% and 33. 7%, respectively. The unchanged nirmatrelvir contained 86. 5 percent of the normalized drug-related substance containing a carboxylic acid metabolite M5, which is derived from hydrolysis of the P2 amide bond and present at 12. 1% of dose. In cultures of human gut microflora, nirmatrelvir hydrolysis to M5 and M8 was shown to occur. This award-winning demonstration of quantitative 19 F-NMR spectroscopy analysis of fluorine-containing compounds early in drug discovery leads to a mass-balance, excretion, and metabolic profile of nirmatrelvir.

Source link: https://europepmc.org/article/MED/35678736


Utility of iPSC-Derived Cells for Disease Modeling, Drug Development, and Cell Therapy.

"As such, the use of iPSCs in drug research and validation has seen a dramatic rise in the last 15 years. " "We'll examine the methods used in generating iPSC-derived cardiomyocytes and neurons for use in disease modeling, drug discovery, and cell therapy. ".

Source link: https://europepmc.org/article/MED/35681550


Clinical Holds in Early Oncology Drug Development

"Analysis of publicly disclosed clinical holds in oncology from 2016 to 2021 identified 39 people in 2013," the author says. Acknowledging the limited sample size and scope of stock market conditions, toxicity-related clinical holds had a dramatic effect on small/medium sized biotechs' market value by a median of -15%, more than large biopharma. These results show that toxicity-related clinical holds are common in early oncology and can have a more detrimental effect on smaller/medium-sized biotech sponsors, particularly in u201d, where public investment in the sector has sluggish.

Source link: https://europepmc.org/article/PPR/PPR503149


Self-emulsifying drug delivery system for oral anticancer therapy: constraints and recent development.

"Oral anticancer therapy has many drawbacks, including inadequate aqueous solubility, poor and irregular absorption from gastro-intestinal organs, high first-pass metabolism, food-influenced absorption, non-targeted delivery, severe systemic and local adverse effects, etc. " An oral bioavailability enhancement may reduce the drug dose and its associated adverse effects. In-vivo solubility and drug absorption from the gastrointestinal tract, bypass liver function by lymphatic absorption, and reduce efflux transport can be enhanced by self-emulsifying drug delivery methods. The SEDDS has achieved promising results for bioavailability and pharmacodynamic response, according to anticancer drug delivery. A handful of researchers have published reports demonstrating the safe loading of anticancer agents in SEDDS-based formulations. Docetaxel, paclitaxel, etoposide, 5 Fluorouracil, doxorubicin, etc. are all common and well-known chemotherapeutic agents such as docetaxel, paclitaxel, etoposide, 5 Fluorouracil, doxorubicin, etc. By SEDDS, you could get an increased bioavailability and reduced dose as a result. No clinical trials have been conducted with anticancer drug-loaded SEDDS. ".

Source link: https://europepmc.org/article/MED/35670356


Development and application of amphotericin B immunoassay for pharmacokinetic studies and therapeutic drug monitoring in critically ill patients.

"Amphotericin B is a broad spectrum antibiotic used to fight severe systemic fungal and protozoan infections. Particularly in critically ill patients, existing and new ATB formulations intended to solve the issue of poor solubility and side effects of ATB require pharmacokinetic studies and dosing controls. In heterologous ELISA, a polyenes ATB, nystatin, natamycin, and deoxycholate ATB was able to distinguish a group of polyenes ATB, nystatin, natamycin, and deoxycholate ATB were identified as 100%, 255, 99%, and 70%, respectively. ATB recovery from spiked serum samples was in the range of 95-96% and unbound ATB fractions in ultrafiltrates of around 12%. In a single COVID-19 patient with secondary lung Rhizopus microspores infection who was treated with ATB and gotten veno-venous extracorporeal membrane oxygenation, PK values were estimated.

Source link: https://europepmc.org/article/MED/35679709


Emerging prospects of protein/peptide-based nanoassemblies for drug delivery and vaccine development

"Proteins have been widely used in the biomedical field due to their well-defined architecture, precise molecular weight, outstanding biocompatibility, and biodegradability, as well as quick-to-function. " Protein/peptide-based nanoassembly makes it the most suitable platform for drug delivery and vaccine manufacturing thanks to these features. In this article, we explore recent advances in subsistent protein/peptide-based nanoassemblies, virus-like particles, self-assemblable natural proteins, and self-assembling artificial peptides. ".

Source link: https://europepmc.org/article/MED/PMC9166156


Pyrazolopyridine - An efficient pharmacophore in recent drug design and development.

Pyrazolopyridine is one of the more popular pharmacophores among the many heterocyclic molecules used for drug design and discovery. Pyrazolopyridine is a result of the synthesis of pyrazole and pyridine rings, which is a result of the fusion of pyrazole and pyridine rings. In a single framework, the potent pharmacology of pyrazolopyridine may be the synergistic effect of pyrazole and pyridine moieties in a single framework. It has become a common problem among elderly people in recent weeks, carcinogens, pollution, and some infectious diseases. Whatever may be the reason, cancer is one of the leading causes of deaths worldwide. Proinflammatory kinases are also identified as the primary target for inflammation reduction. The article is intended to address pharmacology in brief, as well as a structure-activity relationship. The study will highlight the role of pyrazolopyridines in future drug research and discovery, as well as the creation of potent pharmacological agents.

Source link: https://europepmc.org/article/MED/35661410


Development and Application of Adverse Drug Reactions Reports Quality Algorithm (AQUA-12) Score: A Single-Centre Quality Improvement Initiative

"Purpose: To monitor adverse drug reaction reports and evaluate its performance within a quaternary hospital environment, we need a robust assessment device to monitor adverse drug reaction data and assess its effectiveness. " Methods Adverse Drug Reactions Report Quality Algorithm was developed by a multidisciplinary team with experience in ADR management. Independent assessors from both internal and external to the institutional ADR assessment process were rated on three rounds of AQUA-12's reliability, both internal and external to the institutional ADR review process. In all three rounds, the inter-rater reliability of AQUA-12 was found to be excellent. About one out of five people is concerned about immediate hypersensitivity reactions, but delayed hypersensitivity reactions accounted for 60% of all reactions. "AQUA-12 is a versatile and highly reliable assessment device that can be used in hospital settings to regularly track ADR's completeness to aid quality improvement initiatives. ".

Source link: https://europepmc.org/article/PPR/PPR502416


Development and Validation of an HPLC-UV Method for the Quantification of 4'-Hydroxydiclofenac Using Salicylic Acid: Future Applications for Measurement of In Vitro Drug-Drug Interaction in Rat Liver Microsomes.

"Salicylic acid is a key component of nonsteroidal anti-inflammatory drugs that has recently been used for reducing the risk of hospitalization and death among COVID-19 patients and in preventing colorectal cancer by suppressing two primary proteins. " In clinical trials, drug-drug interaction pathways can minimize the occurrence of adverse drug reactions. 4'-hydroxydiclofenac is a CYP2C9 metabolite used as an inhibitor in rat liver microsomes, according to this paper's goal. In a rat liver microsome sample, 4'-hydroxydiclofenac was stable for three days and displayed an acceptable precision and recovery within the ICH recommendations. This method will be useful for future applications of salicylic acid's in vitro inhibitory activity in rat microsomes and in vivo administration of salicylic acid in clinical trials. ".

Source link: https://europepmc.org/article/MED/35684519

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions