Drug repurposing for metabolic disorders: Scientific, technological and economic issues.

Obesity, diabetes, and other metabolic disorders place a huge burden on both the physical health and financial well-being of the community. While the need for effective treatment of metabolic disorders remains urgent and the reality is that traditional drug development involves high costs and a very long time with many pre-clinical and clinical trials, the need for drug repurposing has emerged as a potential alternative. Scientific evidence has shown the anti-diabetic and anti-obesity effects of old drugs, which were initially utilized for the treatment of inflammation, depression, infections, and even cancers. The drug library used modern technological methods to conduct drug screening. Computational molecular docking, genome-wide association studies, or omics data mining are advantageous and unavoidable methods for drug repurposing. Drug repurposing offers a promising avenue for economic efficiency in healthcare, especially for less common metabolic diseases, despite the need for rigorous research and validation. In this chapter, we aim to explore the scientific, technological, and economic issues surrounding drug repurposing for metabolic disorders. We hope to shed light on the potential of this approach and the challenges that need to be addressed to make it a viable option in the treatment of metabolic disorders, especially in the future fight against metabolic disorders.

Photocatalytic degradation of methylene blue under visible light by cobalt ferrite nanoparticles/graphene quantum dots.

A simple approach was developed to synthesize cobalt ferrite nanoparticles/graphene quantum dots (CF/GQDs). The material was prepared from a homogeneous mixture of iron nitrate, cobalt nitrate, and starch at 140, 180 and 200 °C in a 24 h thermal hydrolysis process. The obtained materials were characterised by using X-ray diffraction, scanning electron microscopy, transmission electron microscopy, ultraviolet-visible diffuse reflectance spectroscopy, Fourier-transform infrared spectroscopy, photoluminescence spectroscopy, vibrating-sample magnetometry, and nitrogen adsorption/desorption isotherms. Cobalt ferrite crystals of around 8-10 nm and graphene quantum dots formed directly at 200 °C. Stacking GQDs sheets onto the CF nanoparticles resulted in CF/GQDs nanoparticles. The nanocomposite exhibits satisfactory fluorescent and superparamagnetic properties, which are vital for catalytic applications. The CF/GQDs catalyse significantly the degradation of methylene blue (MB) under visible light. The catalyst can be recycled with an external magnetic field and displays suitable stability. Also, it was reused in three successive experiments with a loss of efficiency of about 5%. The CF/GQDs are considered as an efficient photocatalyst for MB degradation and other dyes.

Cashing in: cost-benefit analysis framework for digital hospitals.

BACKGROUND: For many countries, especially those outside the USA without incentive payments, implementing and maintaining electronic medical records (EMR) is expensive and can be controversial given the large amounts of investment. Evaluating the value of EMR implementation is necessary to understand whether or not, such investment, especially when it comes from the public source, is an efficient allocation of healthcare resources. Nonetheless, most countries have struggled to measure the return on EMR investment due to the lack of appropriate evaluation frameworks. METHODS: This paper outlines the development of an evidence-based digital health cost-benefit analysis (eHealth-CBA) framework to calculate the total economic value of the EMR implementation over time. A net positive benefit indicates such investment represents improved efficiency, and a net negative is considered a wasteful use of public resources. RESULTS: We developed a three-stage process that takes into account the complexity of the healthcare system and its stakeholders, the investment appraisal and evaluation practice, and the existing knowledge of EMR implementation. The three stages include (1) literature review, (2) stakeholder consultation, and (3) CBA framework development. The framework maps the impacts of the EMR to the quadruple aim of healthcare and clearly creates a method for value assessment. CONCLUSIONS: The proposed framework is the first step toward developing a comprehensive evaluation framework for EMRs to inform health decision-makers about the economic value of digital investments rather than just the financial value.

Psychological burden, anxiety, depression and quality of life in patients with hand eczema: A systematic review and meta-analysis.

BACKGROUND: Living with hand eczema (HE) has been associated with impaired quality of life (QoL), having anxiety and depression but the magnitude of association is not clear. OBJECTIVES: The aim of this systematic review and meta-analysis was to determine the psychological burden in terms of anxiety, depression and quality of life in patients with HE. METHODS: Several databases were systematically searched. Weighted means with standard deviation (SD) were calculated for disease severity, QoL, depression and/or anxiety scores among patients with HE. For studies presenting QoL, depression and/or anxiety scores in patients with HE and in controls the weighted means were compared with an unpaired t-test. In studies reporting Hand Eczema Severity Index (HECSI) and Dermatology Life Quality Index (DLQI), the correlation between HECSI and DLQI was estimated using Spearman's rank correlation (rs). RESULTS: In total, 81 studies encompassing 17,835 patients with HE and 31,541 controls were included. The weighted mean DLQI was 10.66 (SD 8.93) corresponding to a moderate-to-large effect on QoL and a strong correlation (rs: 0.76, 95% CI:0.56-0.87) between DLQI and HECSI was observed. The mean EQ-5D-VAS was significantly lower in patients with HE compared with controls (68.03 (SD 10.52) vs. 80.63 (SD 1.17), p < 0.00001). Patients with HE had higher mean HADS (Hospital Anxiety and Depression Scale) anxiety score (7.4 vs. 5.8, p = 0.0008) than controls but not higher HADS depression score (6.5 vs. 5.7, p = 0.32). Only one study assessed risk of anxiety, depression and suicidal ideation showing an increased odds of all diseases among patients with HE compared with controls. CONCLUSION: Hand eczema has a moderate-to-severe impact on quality of life with a strong correlation between disease severity and impact on quality of life. Patients with hand eczema have an impact on QoL comparable to other chronic diseases when measured with generic QoL scoring systems.

CISD3/MiNT is required for complex I function, mitochondrial integrity, and skeletal muscle maintenance.

Mitochondria play a central role in muscle metabolism and function. A unique family of iron-sulfur proteins, termed CDGSH Iron Sulfur Domain-containing (CISD/NEET) proteins, support mitochondrial function in skeletal muscles. The abundance of these proteins declines during aging leading to muscle degeneration. Although the function of the outer mitochondrial CISD/NEET proteins, CISD1/mitoNEET and CISD2/NAF-1, has been defined in skeletal muscle cells, the role of the inner mitochondrial CISD protein, CISD3/MiNT, is currently unknown. Here, we show that CISD3 deficiency in mice results in muscle atrophy that shares proteomic features with Duchenne muscular dystrophy. We further reveal that CISD3 deficiency impairs the function and structure of skeletal muscles, as well as their mitochondria, and that CISD3 interacts with, and donates its [2Fe-2S] clusters to, complex I respiratory chain subunit NADH Ubiquinone Oxidoreductase Core Subunit V2 (NDUFV2). Using coevolutionary and structural computational tools, we model a CISD3-NDUFV2 complex with proximal coevolving residue interactions conducive of [2Fe-2S] cluster transfer reactions, placing the clusters of the two proteins 10 to 16 Å apart. Taken together, our findings reveal that CISD3/MiNT is important for supporting the biogenesis and function of complex I, essential for muscle maintenance and function. Interventions that target CISD3 could therefore impact different muscle degeneration syndromes, aging, and related conditions.

Novel Variant and Known Mutation in 23S rRNA Gene of Mycoplasma pneumoniae, Northern Vietnam, 2023.

During a 2023 outbreak of Mycoplasma pneumoniae-associated community-acquired pneumonia among children in northern Vietnam, we analyzed M. pneumoniae isolated from nasopharyngeal samples. In almost half (6 of 13) of samples tested, we found known A2063G mutations (macrolide resistance) and a novel C2353T variant on the 23S rRNA gene.

Induction of Endoplasmic Reticulum Stress by Prodigiosin in Yeast Saccharomyces cerevisiae.

Prodigiosin, a red pigment produced by numerous bacterial species, exerts various antibiotic effects on prokaryotic and eukaryotic organisms. For instance, human carcinoma cell lines appear to suffer from endoplasmic reticulum (ER) stress in the presence of prodigiosin. Here, we demonstrated that prodigiosin also triggers the unfolded-protein response (UPR), which is a cytoprotective response against ER stress, in yeast Saccharomyces cerevisiae. An S. cerevisiae mutant carrying a UPR-deficient mutation was hypersensitive to prodigiosin. Our observations cumulatively indicate that protein folding in the ER is impaired by prodigiosin, illustrating a new mode of action.

Propagation of a rapid cell-to-cell H2O2 signal over long distances in a monolayer of cardiomyocyte cells.

Cell-to-cell communication plays a cardinal role in the biology of multicellular organisms. H2O2 is an important cell-to-cell signaling molecule involved in the response of mammalian cells to wounding and other stimuli. We previously identified a signaling pathway that transmits wound-induced cell-to-cell H2O2 signals within minutes over long distances, measured in centimeters, in a monolayer of cardiomyocytes. Here we report that this long-distance H2O2 signaling pathway is accompanied by enhanced accumulation of cytosolic H2O2 and altered redox state in cells along its path. We further show that it requires the production of superoxide, as well as the function of gap junctions, and that it is accompanied by changes in the abundance of hundreds of proteins in cells along its path. Our findings highlight the existence of a unique and rapid long-distance H2O2 signaling pathway that could play an important role in different inflammatory responses, wound responses/healing, cardiovascular disease, and/or other conditions.

Fractionation, identification of chemical constituents, and biological properties of cashew (Anacardium occidentale L.) leaf extracts.

The current study aimed to identify the chemical constituents and bioactivities of the crude ethanolic extract (CEE) and its fractions (ethyl acetate (EAF), hexane (HEF), and aqueous (AEF)) from leaves of cashew (Anacardium occidentale L.) grown in Vietnam. A total of 31 compounds which belong to alkanes, hydrocarbons, iodine, terpenoids, phenolics, and flavonoids were determined by a gas chromatography-mass spectrometry (GC-MS) analysis, with bis(2-ethylhexyl) phthalate being the most prevailing compound. The highest total phenolic and flavonoid contents were obtained in the EAF, followed by HEF, CEE, and AQF. All samples showed promising in vitro antibacterial activity, enzyme inhibition, and anticancer activity. Among the samples tested, the EAF exhibited the highest enzyme inhibition activity against α-amylase and α-glucosidase (IC50 values of 51.24 µg/mL and 99.29 µg/mL, respectively), cytotoxicity activity against HeLa cells (IC50 value of 79.49 µg/mL), and antibacterial activity against Bacillus subtilis and Escherichia coli with MIC values of 5 mg/mL and 2.5 mg/mL, respectively. These findings suggest that the leaves of A. occidentale cultivated in Vietnam are a promising source of bioactive components and that EAF is a promising bioactive material warranting further pharmaceutical investigation.

CISD3 is required for Complex I function, mitochondrial integrity, and skeletal muscle maintenance.

Mitochondria play a central role in muscle metabolism and function. In skeletal muscles, a unique family of iron-sulfur proteins, termed CISD proteins, support mitochondrial function. The abundance of these proteins declines with aging leading to muscle degeneration. Although the function of the outer mitochondrial proteins CISD1 and CISD2 has been defined, the role of the inner mitochondrial protein CISD3, is currently unknown. Here we show that CISD3 deficiency in mice results in muscle atrophy that shares proteomic features with Duchenne Muscular Dystrophy. We further reveal that CISD3 deficiency impairs the function and structure of skeletal muscle mitochondria, and that CISD3 interacts with, and donates its clusters to, Complex I respiratory chain subunit NDUFV2. These findings reveal that CISD3 is important for supporting the biogenesis and function of Complex I, essential for muscle maintenance and function. Interventions that target CISD3 could therefore impact muscle degeneration syndromes, aging, and related conditions.

Development and Evaluation of Self-Microemulsifying Drug Delivery System for Improving Oral Absorption of Poorly Water-Soluble Olaparib.

The purpose of this study is to develop and evaluate a self-microemulsifying drug delivery system (SMEDDS) to improve the oral absorption of poorly water-soluble olaparib. Through the solubility test of olaparib in various oils, surfactants and co-surfactants, pharmaceutical excipients were selected. Self-emulsifying regions were identified by mixing the selected materials at various ratios, and a pseudoternary phase diagram was constructed by synthesizing these results. The various physicochemical properties of microemulsion incorporating olaparib were confirmed by investigating the morphology, particle size, zeta potential, drug content and stability. In addition, the improved dissolution and absorption of olaparib were also confirmed through a dissolution test and a pharmacokinetic study. An optimal microemulsion was generated in the formulation of Capmul® MCM 10%, Labrasol® 80% and PEG 400 10%. The fabricated microemulsions were well-dispersed in aqueous solutions, and it was also confirmed that they were maintained well without any problems of physical or chemical stability. The dissolution profiles of olaparib were significantly improved compared to the value of powder. Associated with the high dissolutions of olaparib, the pharmacokinetic parameters were also greatly improved. Taken together with the results mentioned above, the microemulsion could be an effective tool as a formulation for olaparib and other similar drugs.

Recent Advances in Intranasal Liposomes for Drug, Gene, and Vaccine Delivery.

Liposomes are safe, biocompatible, and biodegradable spherical nanosized vesicles produced from cholesterol and phospholipids. Recently, liposomes have been widely administered intranasally for systemic and brain delivery. From the nasal cavity, liposome-encapsulated drugs and genes enter the systemic circulation primarily via absorption in the respiratory region, whereas they can be directly transported to the brain via the olfactory pathway. Liposomes can protect drugs and genes from enzymatic degradation, increase drug absorption across the nasal epithelium, and prolong the residence time in the nasal cavity. Intranasal liposomes are also a potential approach for vaccine delivery. Liposomes can be used as a platform to load antigens and as vaccine adjuvants to induce a robust immune response. With the recent interest in intranasal liposome formulations, this review discusses various aspects of liposomes that make them suitable for intranasal administration. We have summarized the latest advancements and applications of liposomes and evaluated their performance in the systemic and brain delivery of drugs and genes administered intranasally. We have also reviewed recent advances in intranasal liposome vaccine development and proposed perspectives on the future of intranasal liposomes.

Assessment of cyclic volatile methyl siloxanes (CVMSs) in indoor dust from different micro-environments in northern and central Vietnam.

Comprehensive studies on emerging contaminants like volatile methyl siloxanes in settled dust from different micro-environments are still limited. In this study, concentrations and distribution of cyclic volatile methyl siloxanes (CVMSs) including D3, D4, D5, and D6 were examined in indoor dust samples collected from various micro-environments in northern and central Vietnam. Concentrations of total CVMSs in the dust samples ranged from 86.0 to 5890 (median 755) ng/g and decreased in the order: waste processing workshops (median 1560; range 329-5890) > common houses (650; 115-1680) > university classrooms (480; 86.0-1540) > vehicle repair shops (295; 126-1950) ng/g. This observation suggests that informal waste processing activities are sources of CVMSs. Among the studied CVMSs, D5 was the most predominant compound (41 ± 14%), followed by D6 (26 ± 13%), D4 (23 ± 12%), and D3 (11 ± 11%). Moderate positive correlations between D3/D4, D4/D5, and D5/D6 were found. Median daily intake doses of D3, D4, D5, and D6 through dust ingestion were 0.016, 0.051, 0.11, and 0.054 ng/kg/d, respectively, which were comparable to water consumption and markedly lower than the air inhalation pathway.

Propagation of a rapid cell-to-cell H 2 O 2 signal over long distances in a monolayer of cardiomyocyte cells.

Cell-to-cell communication plays a cardinal role in the biology of multicellular organisms. H 2 O 2 is an important cell-to-cell signaling molecule involved in the response of mammalian cells to wounding and other stimuli. We previously identified a signaling pathway that transmits wound-induced cell-to-cell H 2 O 2 signals within minutes over long distances, measured in centimeters, in a monolayer of cardiomyocytes. Here we report that this long-distance H 2 O 2 signaling pathway is accompanied by enhanced accumulation of cytosolic H 2 O 2 and altered redox state in cells along its path. We further show that it requires the production of superoxide, as well as the function of gap junctions, and that it is accompanied by changes in the abundance of hundreds of proteins in cells along its path. Our findings highlight the existence of a unique and rapid long-distance H 2 O 2 signaling pathway that could play an important role in different inflammatory responses, wound responses/healing, cardiovascular disease, and/or other conditions. Highlights: Wounding induces an H 2 O 2 cell-to-cell signal in a monolayer of cardiomyocytes. The cell-to-cell signal requires H 2 O 2 and O 2 · - accumulation along its path. The signal propagates over several centimeters changing the redox state of cells.Changes in the abundance of hundreds of proteins accompanies the signal.The cell-to-cell signal requires paracrine and juxtacrine signaling.

The Effects of One-Point Mutation on the New Delhi Metallo Beta-Lactamase-1 Resistance toward Carbapenem Antibiotics and ß-Lactamase Inhibitors: An In Silico Systematic Approach.

Antibiotic resistance has been becoming more and more critical due to bacteria's evolving hydrolysis enzymes. The NDM-1 enzyme could hydrolyze not only carbapenems but also most of ß-lactam's antibiotics and inhibitors. In fact, variant strains could impose a high impact on the resistance of bacteria producing NDM-1. Although previous studies showed the effect of some variants toward antibiotics and inhibitors binding, there has been no research systematically evaluating the effects of alternative one-point mutations on the hydrolysis capacity of NDM-1. This study aims to identify which mutants could increase or decrease the effectiveness of antibiotics and ß-lactamase inhibitors toward bacteria. Firstly, 35 different variants with a high probability of emergence based on the PAM-1 matrix were constructed and then docked with 5 ligands, namely d-captopril, l-captopril, thiorphan, imipenem, and meropenem. The selected complexes underwent molecular dynamics simulation and free energy binding estimation, with the results showing that the substitutions at residues 122 and 124 most influenced the binding ability of NDM-1 toward inhibitors and antibiotics. The H122R mutant decreases the binding ability between d-captopril and NDM-1 and diminishes the effectiveness of this antibiotic toward Enterobacteriaceae. However, the H122R mutant has a contrary impact on thiorphan, which should be tested in vitro and in vivo in further experiments.

Apply MIKE 11 model to study impacts of climate change on water resources and develop adaptation plan in the Mekong Delta, Vietnam: a case of Can Tho city.

Can Tho city in the Mekong Delta is in the top ten areas affected by climate change. Therefore, assessing climate change impacts, social and economic activities require proposed solutions to respond to climate change. This study aims to (i) apply the MIKE 11 model (Hydrodynamic module and Advection-Dispersion module) to simulate the impacts of climate change scenarios on water resources in Can Tho city; (ii) calculate water balance in Can Tho city; and (iii) suggest climate change adaptation plan for sustainable social-economic activities of the city. The results show that when the rainfall changes due to climate change, the flow rate tends to decrease at high tide and increase at low tide. When the sea level rises due to climate change, the flow rate tends to increase at high tide and decrease at low tide. For 2030, the flow will decrease up to 15.6% and 14.3% at the low tide period for RCP 2.6 and RCP 8.5 compared to the present, respectively. The flow will increase up to 63.5% and 58.9% at the high tide period for RCP 2.6 and RCP 8.5 compared to the present, respectively. The water demand evaluation shows that the water resource reserve in Can Tho city meets water demands in current and future scenarios under climate change. While rainwater and groundwater can provide enough water in the rainy season, the city has to use surface water during the dry season due to a lack of rainwater. Of these, agriculture contributes the most water demands (85%). Eight adaptation measures to climate change for Can Tho city are developed from 2021 to 2050.

Inhibitory effect of 20(S)-protopanaxadiol on cytochrome P450: Potential of its pharmacokinetic interactions in vivo.

20(S)-Protopanaxadiol [20(S)-PPD] is a fully deglycosylated ginsenoside metabolite produced by the gut microbiota in the gastrointestinal tract. Although diverse pharmacological effects have been reported, information on the pharmacokinetic interactions of 20(S)-PPD with cytochrome P450s (CYPs) remains limited. Therefore, the inhibitory potential of 20(S)-PPD on CYP enzymes, which mainly contribute to drug pharmacokinetics, was investigated in this study. The inhibitory effect of 20(S)-PPD was strong for CYP3A4 and moderate for CYP2B6 in human liver microsomes. 20(S)-PPD inhibited Cyp3a and Cyp2b in mouse liver microsomes with a potency similar to that in humans. The solubility of 20(S)-PPD in the artificial intestinal fluid was close to IC50 values of Cyp3a and Cyp2b in the mouse intestine. Systemic exposure to buspirone (Cyp3a specific substrate) and bupropion (Cyp2b specific substrate) increased significantly, whereas the area under the plasma concentration-time curve (AUC) ratio of metabolite to parent drug decreased significantly when co-administered with 20(S)-PPD in mice. The pharmacokinetics of felodipine, a widely used anti-hypertensive agent metabolized mainly by Cyp3a, was also altered following 20(S)-PPD treatment in mice. In conclusion, 20(S)-PPD likely affects the in vivo metabolism of CYP3A4 or CYP2B6 substrates, suggesting a need for careful attention when concomitantly administering 20(S)-PPD with other medications. This study will broaden our understanding of ginseng and products containing precursor ginsenosides of 20(S)-PPD for safer and more efficient use in humans.

Thermal Stability of Fructooligosaccharides Extracted from Defatted Rice Bran: A Kinetic Study Using Liquid Chromatography-Tandem Mass Spectrometry.

Thermal degradation kinetics of fructooligosaccharides (FOS) in defatted rice bran were studied at temperatures of 90, 100, and 110 °C. FOS extracted from rice bran and dissolved in buffers at pH values of 5.0, 6.0, and 7.0 were prepared for the thermal treatments. The residual FOS (including 1-kestose (GF2), nystose (GF3), and 1F-fructofuranosylnystose (GF4)) contents were determined using the ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) method. The results showed that the thermal degradation kinetics of GF2, GF3, and GF4 followed a first-order kinetic model. Thermal degradation rate constants (k values) of GF2, GF3, and GF4 at different temperature and pH values were estimated using the first-order kinetic equation and SAS 9.1. As a result, these k values decreased gradually as the pH of the sample increased from 5.0 to 7.0. The Arrhenius model was applied to describe the heat dependence of the k-values. The activation energy (Ea) was calculated for each case of GF2, GF3, and GF4 degradation at pH values of 5.0, 6.0, and 7.0. The result showed that rice bran FOS is very thermostable at neutral pH while more labile at acidic pH.

Study on the Anticancer Activity of Prodigiosin from Variants of Serratia Marcescens QBN VTCC 910026.

Prodigiosin (Pg), a secondary metabolism produced by numerous bacterial species, is known as anticancer, antibacterial, antifungal, immunosuppressant, antioxidant, antimalarial properties. Pg has been tested for antitumor activity in many different cancer cell lines but studies in LU-1, KB cell lines, and tumor-bearing mice are still limited. In this study, Serratia marcescens QBN VTCC 910026 strain (GenBank: KX674054.1) was mutated using Ethyl Methanesulfonate (EMS) to increase the production of Pg. One strain known as EMS 5 was capable of increasing prodigiosin biosynthetic yield by 52% when compared to the wild-type strain. Red bacterial pigmented colonies containing Pg were collected from solid media, lysed with acetone, purified with toluene: ethyl acetate at a ratio of 9: 1 (v/v), and then used to evaluate the potential anticancer activity. The purity of Pg was confirmed using a high-performance liquid chromatography (HPLC) method which indicated a 98% rate. Pg chemical formula which was determined using 1H-NMR and 13C-NMR spectroscopy, confirmed as prodigiosin (Pg). Human breast cancer cell lines MCF-7, oropharyngeal cancer KB, and particularly lung cancer LU-1 in vitro were used to test the anticancer activity of purified Pg compound. It showed a strong inhibitory ability in all the cancer cell lines. Furthermore, the isolated Pg had capable of inhibiting tumor growth, the tumor volume decreased by 36.82%, after 28 days. The results indicated that the bacterial prodigiosin from variants Serratia marcescens QBN VTCC 910026 strain is an encouraging fragment suitable for therapeutic applications.

Development of an LC-MS/MS Method for ARV-110, a PROTAC Molecule, and Applications to Pharmacokinetic Studies.

ARV-110, a novel proteolysis-targeting chimera (PROTAC), has been reported to show satisfactory safety and tolerability for prostate cancer therapy in phase I clinical trials. However, there is a lack of bioanalytical assays for ARV-110 determination in biological samples. In this study, we developed and validated an LC-MS/MS method for the quantitation of ARV-110 in rat and mouse plasma and applied it to pharmacokinetic studies. ARV-110 and pomalidomide (internal standard) were extracted from the plasma samples using the protein precipitation method. Sample separation was performed using a C18 column and a mobile phase of 0.1% formic acid in distilled water-0.1% formic acid in acetonitrile (30:70, v/v). Multiple reaction monitoring was used to quantify ARV-110 and pomalidomide with ion transitions at m/z 813.4 → 452.2 and 273.8 → 201.0, respectively. The developed method showed good linearity in the concentration range of 2-3000 ng/mL with acceptable accuracy, precision, matrix effect, process efficiency, and recovery. ARV-110 was stable in rat and mouse plasma under long-term storage, three freeze-thaw cycles, and in an autosampler, but unstable at room temperature and 37 °C. Furthermore, the elimination of ARV-110 via phase 1 metabolism in rat, mouse, and human hepatic microsomes was shown to be unlikely. Application of the developed method to pharmacokinetic studies revealed that the oral bioavailability of ARV-110 in rats and mice was moderate (23.83% and 37.89%, respectively). These pharmacokinetic findings are beneficial for future preclinical and clinical studies of ARV-110 and/or other PROTACs.