Abstract:Nortrachelogenin is a dibenzylbutyrolactone lignan associated with redox-sensitive signaling. We examined its effects on receptor activator of nuclear factor kappa-B ligand (RANKL)-induced nuclear factor kappa-B (NF-κB) activation in osteoclast precursors. Nortrachelogenin attenuated IκB phosphorylation and degradation and reduced p65 phosphorylation. Consistently, it markedly decreased the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclasts. These findings identify nortrachelogenin as a lignan scaffold that suppresses nuclear factor kappa-B signaling and osteoclastogenesis in vitro.
Abstract Antiviral drugs are pivotal in the prevention and management of infections caused by viruses, ranging from common cold viruses to life-threatening pathogens like human immunodeficiency virus, hepatitis viruses, Ebola virus, etc. Furthermore, antiviral therapy is increasingly being integrated into the management of chronic viral infections to restrain their replication, avert disease progression, and minimize the risk of complications. The availability of newer generations of antiviral drugs, particularly direct-acting antivirals, and combination therapies have significantly improved treatment outcomes, offering better cure speed, shorter treatment time, and reduced side effects as compared to older-generation antivirals. This comprehensive review provides an in-depth analysis of the diverse classes of antiviral drugs, their mechanisms of action, clinical applications, challenges, and future directions. With a focus on recent advancements and emerging trends, the current landscape of antiviral drug development and its implications for global public health are also discussed.
Background:Heart failure is a significant global health burden. This study aims to identify heart failure-associated genes through transcriptome-wide association studies combined with genome-wide association studies. Methods:A transcriptome-wide association study was conducted using Functional Summary-based Imputation, integrating heart failure genome-wide association study summary data (47,309 cases and 930,014 controls) with Genotype-Tissues Expression Project V8 expression quantitative trait loci data from 49 tissues. Gene-level analysis was performed using Multi-marker Analysis of Genomic Annotation, followed by mendelian randomization and Bayesian colocalization. The functional implications of candidate genes were explored using GeneMANIA, and the druggability of the top gene, USP36, was evaluated via molecular docking simulations. Results:Functional Summary-based Imputation and Multi-marker Analysis of Genomic Annotation analyses identified 26 candidate genes. Further investigation highlighted USP36 as significant, particularly in left ventricular tissue, where it confers protection against heart failure. GeneMANIA showed that USP36 interacts with genes involved in oxidative stress-induced apoptosis, suggesting its role in heart failure pathogenesis. Molecular docking simulations confirmed USP36's binding affinity with heart failure therapeutics, supporting its potential as a therapeutic target. Conclusions:USP36 is a novel heart failure susceptibility gene and a promising therapeutic target. Its involvement in oxidative stress-related pathways offers new insights into heart failure risk and warrants further investigation for disease development and treatment.
Diabetes mellitus (DM) is a chronic metabolic disorder that continues to pose a major healthcare challenge worldwide. Despite the availability of several therapeutic options, achieving sustained glycaemic control and preventing long-term complications remain difficult in many patients. Walnut (Juglans regia L.) has gained attention as a potential complementary approach because of its diverse bioactive constituents and reported metabolic benefits. This review discusses the mechanistic, preclinical, and clinical evidence supporting the role of J. regia in diabetes management. The available studies indicate that walnut contains several phytochemicals, including juglone, flavonoids, polyphenols, and polyunsaturated fatty acids, which may contribute to antioxidant, anti-inflammatory, and insulin-sensitizing activities. Experimental findings suggest that these constituents help improve glucose homeostasis, protect pancreatic β-cells, and regulate insulin-signalling pathways. Preclinical studies consistently demonstrate beneficial effects on glycaemic parameters and pancreatic function, while clinical investigations report modest improvements in fasting blood glucose, HbA1c, and lipid profiles with good tolerability. However, differences in extract preparation, dosage, study design, and duration limit direct comparison among studies and highlight the need for further standardization. Future research should focus on well-designed clinical trials, optimized dosing strategies, and the evaluation of walnut preparations as adjuncts to conventional antidiabetic therapy. Overall, the current evidence supports J. regia as a promising complementary candidate for diabetes management and provides a basis for its further clinical development.
Objective:This study aimed to explore the spectrum of adverse events associated with hydroxyprogesterone and provide a comprehensive understanding of the drug's safety profile based on the Food and Drug Administration's Adverse Event Reporting System database. Methods:Adverse events associated with hydroxyprogesterone were extracted from the Food and Drug Administration's Adverse Event Reporting System database, covering the period from the first quarter of 2004 to the second quarter of 2025. Disproportionality analysis methods were used to detect potential safety signals related to hydroxyprogesterone. We further analyzed the demographic characteristics of the population and the onset time of adverse events. Results:A total of 40,450 adverse event reports related to hydroxyprogesterone were included, corresponding to 197 significant preferred terms categorized into 21 system organ classes per Medical Dictionary for Regulatory Activities criteria. In addition to commonly observed adverse events, several clinically relevant adverse events not previously documented were identified, including fetal distress syndrome, abnormal fetal heart rate deceleration, neonatal jaundice, neonatal respiratory distress, and low birth weight infant. The median time to the onset of hydroxyprogesterone-induced adverse events was 20 days (interquartile range: 0-72 d), with 57.8% of adverse events occurring within the initial 30 days following hydroxyprogesterone administration. Conclusions:In this study, we identified both clinically observed adverse events and potential safety signals associated with hydroxyprogesterone. These results provide valuable evidence to support clinical monitoring, safety risk identification, and the development of subsequent safety investigations.
Abstract:Alpelisib (BY719) is a phosphoinositide-3-kinase inhibitor that specifically targets phosphoinositide-3-kinase-alpha. This enzyme is part of the phosphoinositide-3-kinase/α-serine/threonine-protein kinase/mammalian target of rapamycin signaling pathway, which promotes cell growth and survival. Mutations in the phosphoinositide-3-kinase gene cause the phosphoinositide-3-kinase signaling pathway to become overactive, leading to uncontrolled cell growth and survival, which contributes to tumor development. By inhibiting phosphoinositide-3-kinase-alpha, alpelisib can slow tumor growth and kill cancer cells. The goal of this study was to develop and validate a new, sensitive, specific, and rapid liquid chromatography-tandem mass spectrometry method for measuring alpelisib in dried blood spots from both mice and humans. Filgotinib served as the internal standard, and all procedures adhered to regulatory standards. Alpelisib and the internal standard were measured using a Sciex triple quadrupole mass spectrometer in multiple reaction monitoring mode with positive-ion detection. The focus was on the parent-daughter mass-to-charge transitions of m/z 442.0→327.9 for alpelisib and m/z 426.2→291.2 for the internal standard. The linear range for alpelisib was 0.331-1026 ng/mL (r>0.990). This method successfully characterized the in vitro metabolic profiles and in vivo pharmacokinetics of alpelisib in mice. A strong correlation was found between dried blood spots and plasma concentrations, suggesting that dried blood spots can serve as an alternative to plasma for pharmacokinetic analysis.
Objective:Astragalus polysaccharide (APS) has therapeutic potential for neurodegenerative diseases; however, its specific mechanism of action against ischemic stroke (IS) requires further elucidation. This study aimed to elucidate the protective effects of APS on neural tissue and to explore the underlying molecular pathways in a rat population subjected to middle cerebral artery occlusion (MCAO). Methods:The animals received intraperitoneal (IP) injections of APS. Neurological recovery was assessed using neurobehavioral tests, and neuronal morphology was examined using Nissl staining. Then, we assessed the mRNA levels of IL-1β, IL-6, and TNF-α as well as the concentrations of oxidative stress-related substances. Finally, we evaluated the expression levels of Nrf2, Keap1, HO-1, and GPX4 through Western blotting and immunofluorescence. Results:APS improved neurological function and ameliorated neuronal damage. It concurrently inhibited IL-1β, IL-6, and TNF-α expression while enhancing antioxidative potential. Mechanistically, APS induced an elevation in the levels of Nrf2, HO-1, and GPX4 proteins while concurrently causing a reduction in the protein levels of Keap1 in the striatum. Conclusions:APS effectively mitigated neuronal damage and motor dysfunction after cerebral ischemia. The protective mechanism involves the activation of the Nrf2/HO-1 axis and subsequent suppression of oxidative stress and neuroinflammation.
Background:Human fibrinogen concentrate is used as replacement therapy for congenital and acquired fibrinogen deficiencies. Despite similar manufacturing principles, compositional differences among products may affect clot quality and hemostatic efficacy. BT524 (Biotest) is a newly developed human fibrinogen concentrate with proven clinical safety and efficacy. Objectives:The objective of this study was to compare the biochemical composition and in vitro functional characteristics of BT524 with those of two commercially available plasma-derived fibrinogen concentrates (Products I and II). Methods:Three independent batches of each human fibrinogen concentrate were analyzed for the total and clottable protein, fibrinogen antigen, fibrinogen activity by Clauss, clotting factors, degradation markers (fibrinopeptide A and D-dimer), sub-visible particles, and aggregates. Maximum clot firmness and dynamics were assessed using rotational thromboelastometry (fibrin-based thromboelastometry). Fibrinogen deficient plasma with low factor XIII content was spiked each fibrinogen concentrate and increasing concentrations of factor XIII (0-0.8 U/mL). Results:BT524 showed consistent fibrinogen content but contained no active factor VIII, factor XIII, or von Willebrand factor, indicating a precisely defined composition. Levels of degradation markers, aggregates, and sub-visible particles were markedly lower than in comparator products, reflecting the superior biochemical purity of BT524. BT524 achieved significantly higher maximum clot firmness than Product I (p<0.0001) and demonstrated comparable performance with Product II. Spiking of factor XIII resulted in an additional increase in maximum clot firmness in BT524 and Product II, but not in Product I, proving functional factor XIII susceptibility of BT524. Conclusions:BT524 demonstrates high biochemical purity and robust functional clot formation. These findings highlight that fibrinogen concentrates differ in composition, functionality and molecular integrity, which determines clot quality and hemostatic performance.
Abstract:Vodobatinib (K0706) is a novel, orally bioavailable Bcr-Abl 1 tyrosine kinase inhibitor designed to overcome resistance mutations such as T3151 in chronic myeloid leukemia. While its clinical efficacy and safety are under investigation, there is limited information on vodobatinib preclinical absorption, distribution, metabolism, and excretion properties and tissue distribution. The objective of this study is to evaluate vodobatinib solubility in phosphate buffer and biorelevant media, metabolic stability in liver microsomes and hepatocytes across species, permeability using MDCK-MDR1 cells, plasma protein binding via equilibrium dialysis, CYP phenotyping and CYP inhibition. Tissue distribution was assessed in male Sprague-Dawley rats following oral administration (2.0 mg/kg), with plasma and tissue samples collected over a 24-hour period. Vodobatinib exhibited poor solubility in phosphate buffer (2.5 µM), but showed improved solubility in biorelevant media. It demonstrated high metabolic stability in liver microsomes and hepatocytes of rats and dogs, with moderate stability in humans. Permeability studies indicated low efflux liability. Plasma protein binding was extensive (>99.8%) across species. Metabolism was primarily mediated by CYP3A4 (≈70%), with minor involvement from CYP2C19 and CYP2D6. CYP inhibition was weak to moderate, suggesting a low potential for drug-drug interactions. Vodobatinib showed high distribution to the liver, intestines, and kidneys, with low brain penetration. Vodobatinib demonstrates a favorable preclinical absorption, distribution, metabolism, and excretion profile, with high metabolic stability, minimal efflux liability, and selective tissue distribution. These findings support its continued clinical development in chronic myeloid leukemia and potentially other Bcr-Abl 1 driven malignancies.
Abstract:Doxorubicin, a widely used chemotherapeutic agent, is clinically limited by its dose-dependent cardiotoxicity, in which cardiomyocyte ferroptosis has recently been identified as a critical pathogenic mechanism. Consequently, targeting myocardial ferroptosis has emerged as a promising strategy to reduce doxorubicin-induced cardiac injury. Ellagic acid, a naturally occurring polyphenolic compound, possesses potent antioxidant and anti-inflammatory properties that contribute to its cytoprotective effects. This study aimed to investigate the protective role of ellagic acid against doxorubicin-induced cardiomyocyte ferroptosis and elucidate its underlying mechanisms. Using H9C2 cells and human-induced pluripotent stem cell-derived cardiomyocytes, we established in vitro models of doxorubicin-induced cardiac ferroptosis. Ellagic acid treatment markedly upregulated the expression of anti-ferroptosis proteins, reduced reactive oxygen species accumulation, and alleviated lipid peroxidation, thereby suppressing doxorubicin-triggered ferroptosis. Moreover, the anti-ferroptosis effects of ellagic acid were validated in vivo. Mechanistically, these cardioprotective actions were mediated through the activation of the nuclear factor erythroid 2-related factor 2 signaling pathway. In conclusion, our findings identify ellagic acid as a novel nuclear factor erythroid 2-related factor 2 activator that protects against doxorubicin-induced cardiotoxicity by inhibiting ferroptosis in cardiomyocytes.
Background:Sex and fed state are critical factors influencing drug pharmacokinetics, potentially affecting efficacy and safety. This study evaluates the impact of sex and food intake on key pharmacokinetics parameters-maximum plasma concentration, time to maximum plasma concentration, area under the curve to last time point, area under the curve extrapolated to infinity, and elimination half-life-for amlodipine, dapagliflozin, empagliflozin, rivaroxaban, deferiprone, deflazacort, and siponimod. Methods:Pooled data from clinical studies were analyzed. Geometric mean values and coefficients of variation were calculated for men and women. Statistical comparisons were performed using appropriate tests to derive p-values for sex (men vs women) and fed state (fasting vs fed) differences. Results:Significant sex-based differences were observed. Women exhibited significantly higher systemic exposure (the maximum plasma concentration and area under the curve) for amlodipine, dapagliflozin, empagliflozin, rivaroxaban (in the fed state and overall), deferiprone (overall and fed), and siponimod (overall and fasting). The time to the maximum plasma concentration was significantly faster for deflazacort in women. Fed state comparisons showed that food significantly increased the time to the maximum plasma concentration for deferiprone in both sexes and rivaroxaban in women, while decreasing the maximum plasma concentration for rivaroxaban in both sexes. Conclusions:Sex and fed state significantly influence the pharmacokinetics of several drugs. These findings underscore the necessity of considering these factors in clinical dosing regimens and drug development to optimize therapeutic outcomes.
Background:Doxorubicin, an anti-neoplastic agent, is linked with a risk of cardiotoxicity following acute or cumulative doses. Protocatechuic acid ethyl ester, as a natural phenolic acid derivative, inhibits a prolyl hydroxylase enzyme with iron-chelating and antioxidative properties. This study evaluated the effects of protocatechuic acid ethyl ester on cardiotoxicity induced by doxorubicin in an animal model. Methods:Male Wistar rats were pretreated orally with 50, 75, and 150 mg/kg of protocatechuic acid ethyl ester for 14 days. Cardiotoxicity was induced by the acute injection of doxorubicin (20 mg/kg) on the 10th day. Recording of the electrocardiogram, assessment of serum parameters of aspartate aminotransferase, lactate dehydrogenase, creatine phosphokinase-MB, malondialdehyde and total antioxidant capacity as ferric reducing antioxidant power, and histopathological inspection of heart tissues were performed. Results:Protocatechuic acid ethyl ester at all doses prevented the increase in heart rate and the decrease in the R-R interval induced by doxorubicin. Higher doses of protocatechuic acid ethyl ester (75 and 150 mg/kg) were able to improve most of the serum and tissue parameters of cardiac injury. Protocatechuic acid ethyl ester at a dose of 150 mg/kg significantly reduced lactate dehydrogenase (p<0.01), aspartate aminotransferase, creatine phosphokinase-MB, and heart weight (p<0.001) and improved histopathological changes. It markedly reversed oxidative insult through decreasing malondialdehyde (p<0.01) and increasing ferric reducing antioxidant power (p<0.05). Conclusions:Findings of this study indicated that protocatechuic acid ethyl ester has noteworthy potential to mitigate the cardiotoxicity associated with doxorubicin, possibly through alleviating oxidative stress.
Background and objective:Glioblastoma is one of the most frequently seen cancer types in the central nervous system, which is associated with drug resistance and high mortality rates. Curcumin demonstrates significant anticancer potential by inhibiting crucial processes, such as cell proliferation and metastasis, positioning it as a candidate for targeted treatment strategies. In this study, the potential of curcumin to overcome temozolomide resistance in U87 glioblastoma cells was examined, with a focus on elucidating the underlying molecular pathways. Methods:U87 and U87/TMZ cells were treated with different concentrations of curcumin, temozolomide, and their combination for 24 and 48 hours, and the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to assess viability. The expression of key genes and proteins of the Bax, Bcl-2, caspase-3, O6-methylguanine-DNA methyltransferase, and DNA repair genes, including MSH2, MSH6, and PARP1, was evaluated by quantitative real-time polymerase chain reaction and western blot. Also, the activity of caspase-3/7 enzymes and the level of apoptosis were measured by fluorometric methods and enzyme-linked immunosorbent assay. Results:Curcumin significantly decreased temozolomide-resistant U87 cell viability in combination with temozolomide in a dose-dependent manner. The expression of O6-methylguanine-DNA methyltransferase, MSH2, MSH6, and PARP1 genes and proteins was decreased. Also, the increase in Bax expression and caspase activity indicated a strong induction of apoptosis by curcumin in resistant cells. Conclusions:Curcumin mitigates temozolomide resistance in glioblastoma by modulating the O6-methylguanine-DNA methyltransferase/MSH2/MSH6 axis and enhancing apoptosis. This natural compound holds promise as a potential agent for the development of targeted glioblastoma therapies.
Background:Nausea and vomiting are commonly reported side effects of long-term linezolid therapy, which is indispensable for tuberculosis and osteoarticular infections. Since the mechanism underlying the development of nausea and vomiting during linezolid treatment is unknown, this study aimed to explore the mechanisms by focusing on the monoamine oxidase-inhibiting effect of linezolid. Methods:In vitro serotonin release assays were performed using QGP-1 cells as a surrogate for enterochromaffin cells exposed to linezolid, the monoamine oxidase inhibitor clorgyline, and the known emetogenic agent cisplatin. Serotonin concentrations in the solutions were measured using an enzyme-linked immunosorbent assay. Clorgyline and cisplatin were administered simultaneously with linezolid to elucidate the serotonin release mechanism and confirm the synergistic effects. The intracellular Ca2+assays using Fura‑2 were also performed to assess whether serotonin release is mediated by Ca2+‑dependent exocytosis. Results:Linezolid exposure significantly increased serotonin release from QGP-1 cells in concentration- and time-dependent manners. Serotonin release also increased in the clorgyline exposure group, and the release of serotonin in the linezolid/clorgyline co-exposure group was higher than that in the single-exposure groups. In contrast, no significant serotonin release or synergistic effects were observed in the cisplatin/linezolid-exposed groups. The Ca2+assays demonstrated that linezolid exposure did not change intracellular Ca2+levels. Conclusions:Serotonin release was observed when QGP-1 cells were exposed to linezolid, an effect similar to that observed with the potent monoamine oxidase A inhibitor clorgyline. Furthermore, the Ca2+assays indicated that linezolid‑induced serotonin release occurs independently of Ca2+‑dependent exocytosis.
Background:Benign prostatic hyperplasia is a common public health problem in aging men across the globe. Diarylpropionitrile, a selective estrogen receptor-beta agonist, favorably regulates cell proliferation and inflammation, two major hallmarks of benign prostatic hyperplasia pathology. Objective:This study aimed to explore the mitigative impact of diarylpropionitrile on testosterone-induced benign prostatic hyperplasia in rats. Methods:Forty male rats were randomly divided into four groups (n=10): a normal control group, a benign prostatic hyperplasia group, a finasteride-treated group, and a diarylpropionitrile-treated group. After 4 weeks of treatment, macroscopic and microscopic features of prostatic hyperplasia and androgenic, proliferative, angiogenic, apoptotic, and inflammatory biomarkers were assessed. Results:Testosterone administration significantly increased prostate weight, prostatic index, and hyperplasia scores. Both diarylpropionitrile and finasteride effectively ameliorated the benign prostatic hyperplasia lesions by reversing these changes. Both treatments significantly lowered elevated prostatic dihydrotestosterone, 5-αR2, β-catenin, and proliferating cell nuclear antigen levels, demonstrating a strong anti-proliferative effect. They also attenuated the increased pro-inflammatory cytokines interleukin-6, interleukin-27, and prostaglandin E2 and growth factors transforming growth factor beta and vascular endothelial growth factor. Furthermore, both agents inhibited testosterone-induced estrogen receptor-beta upregulation, counteracted peroxisome proliferator-activated receptor gamma tissue protein, and boosted the expression of the anti-apoptotic marker B-cell lymphoma 2. Conclusions:Diarylpropionitrile alleviates testosterone-induced benign prostatic hyperplasia in rats by modulating key pathways associated with cellular proliferation and inflammation. Diarylpropionitrile, as an estrogen receptor-beta agonist, represents a promising alternative for the benign prostatic hyperplasia treatment through multi-targeted mechanisms.
Vitiligo is a cutaneous autoimmune disease characterized by the destruction of epidermal melanocytes leading to white patches with a global prevalence of about 0.5-2%, and patients' quality of life are greatly affected by the change in appearance and social discrimination caused by the disease. Most of the key cytokines in the pathogenesis of vitiligo act through the Janus kinase/signal transducer and activator of transcription signaling pathway, which is an effective therapeutic target. The first generation Janus kinase inhibitors, i.e., tofacitinib and ruxolitinib, inhibit a variety of Janus kinases, whereas the new generation Janus kinase inhibitors, such as ritlecitinib and upadacitinib, exhibit inhibitory effects only on specific Janus kinases; they are therefore selective as well as safer and more effective. In this review, we aim to provide an up-to-date view of vitiligo pathogenesis at the cellular, molecular, and genetic levels and further to elucidate the relationship between Janus kinase/signal transducer and activator of transcription signaling pathway components and vitiligo. Finally, we summarize currently market-approved and preclinical Janus kinase inhibitors, highlighting the latest advances in their clinical applications.
Both eliglustat and miglustat are substrate reduction therapies targeting glucosylceramide synthase; yet, their safety profile has not been comprehensively analyzed. This study analyzes adverse events associated with both drugs using the U.S. Food and Drug Administration Adverse Event Reporting System to provide insights for clinical safety.Adverse events were classified by MedDRA System Organ Class (SOC, v26.1). Adverse event signals were mined by disproportionality analyses, including the reporting odds ratio, the proportional reporting ratio, the multi-item gamma Poisson shrinker algorithms, and the Bayesian confidence propagation neural network.A total of 1,223 and 980 adverse event reports were retrieved from eliglustat and miglustat, respectively, involving 27 System Organ Class categories each. Some positive signals were consistent with the drug labels, including dyspepsia identified in eliglustat and diarrhoea identified in miglustat. We also identified unexpected signals not listed on the drug labels, such as paresthesia, dry skin, and ichthyosis for eliglustat and dysphagia for miglustat. For patients treated with eliglustat and miglustat, the majority of adverse events manifested more than 1 year after the initiation of therapy. Notably, male patients treated with eliglustat have the significantly higher incidence of weight increase and dry skin. Female patients treated with miglustat have the significantly higher incidence of dysphagia and cognitive disorder.In the clinical administration of eliglustat and miglustat, clinicians need to monitor the effects of adverse events varied by gender and to pay more attention to new adverse event signals.
Several studies have shown that some drugs can slow the growth of cancer cells by inhibiting the c-Abl kinase. However, some of these drugs can cause side effects such as gynecomastia, pulmonary toxicity, and lentiginosis, among others. In the search for a therapeutic alternative, some amide derivatives have been developed to treat cancer. However, their interaction with the c-Abl kinase is not clear.The aim of this study was to evaluate the interaction of 28 amide derivatives with the c-Abl kinase as a therapeutic alternative to treat cancer cells.The theoretical interaction of amide derivatives with the c-Abl kinase was carried out using the 1iep protein as a theoretical model. Besides, bosutinib, dasatinib, imatinib, nilotinib, and radotinib were used as controls in the DockingServer program.The results displayed different types of aminoacid residues involved in the interaction of amide derivatives with the 1iep protein surface compared to the controls. In addition, the inhibition constant (Ki) was lower for compounds 15, 16, and 18 compared to radotinib. Finally, the Ki for amide derivatives 1, 19, and 21 were lower compared with bosutinib, dasatinib, imatinib, and nilotinib.Theoretical data indicate that amide derivatives such as 1, 15, 16, 18, 19, and 21 might have a higher affinity for the 1iep protein surface. This phenomenon could be translated as c-Abl kinase inhibition, resulting in a decrease in cancer cell growth.
ABL kinase inhibitors have transformed the clinical management of chronic myelogenous leukemia; yet, the metabolic consequences of their use remain largely unexplored. In the current study, using K562 cell lines, the metabolic impact of five ABL kinase inhibitors, such as imatinib, dasatinib, nilotinib, ponatinib, and axitinib, was studied. Comparative metabolic profiling revealed both common and inhibitor-specific metabolic alterations. Pathway enrichment analysis identified significant downregulation in starch and sucrose metabolism, nucleotide sugar metabolism and sphingolipid metabolism. These results offered insights to guide the development of treatment strategies for overcoming the drug resistance in chronic myelogenous leukemia as well as managing the associated toxicities.
