Drug Development Research最新文献

{"title":"Tirbanibulin (KX2-391) analog KX2-361 inhibits botulinum neurotoxin serotype A mediated SNAP-25 cleavage in pre- and post-intoxication models in cells","authors":"Dilara Koc,&nbsp;Kubra Ibis,&nbsp;Peri Besarat,&nbsp;Erden Banoglu,&nbsp;Erkan Kiris","doi":"10.1002/ddr.22248","DOIUrl":"10.1002/ddr.22248","url":null,"abstract":"<p>Botulinum neurotoxins (BoNT) inhibit neuroexocytosis, leading to the potentially lethal disease botulism. BoNT serotype A is responsible for most human botulism cases, and there are no approved therapeutics to treat already intoxicated patients. A growing body of research has demonstrated that BoNT/A can escape into the central nervous system, and therefore, identification of BoNT/A inhibitors that can penetrate BBB and neutralize the toxin within intoxicated neurons would be important. We previously identified an FDA-approved, orally bioavailable compound, KX2-391 (Tirbanibulin) that inhibits BoNT/A in motor neuron assays. Recently, a structural analog of KX2-391, KX2-361, has been shown to exhibit good oral bioavailability and cross BBB with high efficiency in mouse experiments. Therefore, in this work, we evaluated the inhibitory effects of KX2-361 against BoNT/A. Toward this goal, we first evaluated the compound for its effects on cell viability in PC12 cells, via MTT assay, and in mouse embryonic stem cell (mESC)-derived motor neurons, with imaging-based assays. Following, we tested KX2-361 in mESC-derived motor neurons intoxicated with BoNT/A holotoxin, and the compound exhibited activity against the toxin in both pre- and post-intoxication conditions. Excitingly, KX2-361 also inhibited BoNT/A enzymatic component (light chain; LC) in PC12 cells transfected with BoNT/A LC. Furthermore, our molecular docking analyses suggested that KX2-361 can directly bind to BoNT/A LC. Medicinal chemistry approaches to develop structural analogs of KX2-361 to increase its efficacy against BoNT/A may provide a critical lead compound with BBB penetration capacity for drug development efforts against BoNT/A intoxication.</p>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ddr.22248","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Asiaticoside enhances the effect of propofol on the invasion, ferroptosis and immune escape of bladder cancer","authors":"Ming Jin,&nbsp;Kun He,&nbsp;Shuqing Zhen,&nbsp;Yanqiao Wang,&nbsp;Huifang Guo,&nbsp;Hongxia Shen,&nbsp;Fumin Ping","doi":"10.1002/ddr.22242","DOIUrl":"10.1002/ddr.22242","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>Bladder cancer is a highly prevalent malignancy. Asiaticoside (AC), a triterpenoid derivative, exhibits antitumor effect on different tumors. This study aimed to explore the role and mechanism of AC on bladder cancer. J82 and T24 cells were treated with AC and/or propofol, and nude mice were subcutaneously administrated with T24 cells. The effect and mechanism of AC and/or propofol were explored by cell counting kit-8, transwell, flow cytometry, enzyme-linked immunosorbent assay, immunohistochemistry and western blot assays both in vitro and in vivo. Cell viability of J82 and T24 cells was inhibited by AC with a IC50 value of 2.43 μM and 2.16 μM, and by propofol with a IC50 value of 42.51 μM and 48.37 μM, respectively. AC or propofol alone decreased cell proliferation, invasion, and immune escape with the increased ferroptosis, as well as downregulating the level of the PI3K/AKT pathway in both animal and cell experiments. The effect of propofol on the above-mentioned indicators was further enhanced with the co-treatment of AC in vitro and in vivo. Taken together, AC promoted the ameliorative effect of propofol on bladder cancer involved in PI3K/AKT pathway.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GSTO2 ameliorates human neuroblastoma cell apoptosis, inflammation, ferroptosis, and oxidative stress by upregulating GPX4 expression in intracerebral hemorrhage","authors":"Chaoyi Liu,&nbsp;Weihua Tian,&nbsp;Dan Lei","doi":"10.1002/ddr.22245","DOIUrl":"10.1002/ddr.22245","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>Intracerebral hemorrhage (ICH) is a severe hemorrhagic stroke and induces severe secondary neurological injury. However, its pathogenesis remains to be explored. The present work investigates the role of glutathione S-transferase omega 2 (GSTO2) in ICH and the underlying mechanism. Human neuroblastoma cells (SK-N-SH) were stimulated using hemin to mimic ICH-like injury. Protein expression levels of GSTO2 and glutathione peroxidase 4 (GPX4) were detected by western blot analysis assay. Cell viability was assessed by cell counting kit-8 assay. Cell proliferation was investigated by 5-ethynyl-2′-deoxyuridine assay. Cell apoptosis was analyzed by flow cytometry. Interleukin-6 and tumor necrosis factor-α levels were quantified by enzyme-linked immunosorbent assays. Fe²⁺ colorimetric assay kit was used to detect Fe²⁺ level. A cellular reactive oxygen species (ROS) assay kit was used to detect ROS levels. Malondialdehyde (MDA) level was assessed using the MDA content assay kit. GSH level was quantified using the GSH assay kit. Co-immunoprecipitation assay was performed to identify the association between GSTO2 and GPX4. Hemin stimulation suppressed SK-N-SH cell proliferation and promoted cell apoptosis, cell inflammation, ferroptosis, and oxidative stress. GSTO2 expression was downregulated in hemin-treated SK-N-SH cells in comparison with the control group. In addition, ectopic GSTO2 expression counteracted hemin-induced inhibitory effect on cell proliferation and promoting effects on cell apoptosis, inflammation, ferroptosis, and oxidative stress. Moreover, GSTO2 was associated with GPX4 in SK-N-SH cells. GPX4 silencing attenuated GSTO2 overexpression-induced effects on hemin-stimulated SK-N-SH cell injury. GSTO2 ameliorated SK-N-SH cell apoptosis, inflammation, ferroptosis, and oxidative stress by upregulating GPX4 expression in ICH, providing a therapeutic strategy for ICH.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of sedative activity of fraxin: In vivo approach along with receptor binding affinity and molecular interaction with GABAergic system","authors":"Sonaly Akter Mukty,&nbsp;Rubel Hasan,&nbsp;Md. Shimul Bhuia,&nbsp;Anik Kumar Saha,&nbsp;Umme Sadea Rahman,&nbsp;Mst Muslima Khatun,&nbsp;Sumaya Akter Bithi,&nbsp;Siddique Akber Ansari,&nbsp;Irfan Aamer Ansari,&nbsp;Muhammad Torequl Islam","doi":"10.1002/ddr.22250","DOIUrl":"10.1002/ddr.22250","url":null,"abstract":"<p>Insomnia is a sleep disorder in which you have trouble falling and/or staying asleep. This research aims to evaluate the sedative effects of fraxin (FX) on sleeping mice induced by thiopental sodium (TS). In addition, a molecular docking study was conducted to investigate the molecular processes underlying these effects. The study used adult male Swiss albino mice and administered FX (10 and 20 mg/kg, i.p.) and diazepam (DZP) (2 mg/kg) either separately or in combination within the different groups to examine their modulatory effects. After a period of 30 min, the mice that had been treated were administered (TS: 20 mg/kg, i.p.) to induce sleep. The onset of sleep for the mice and the length of their sleep were manually recorded. Additionally, a computational analysis was conducted to predict the role of gamma-aminobutyric acid (GABA) receptors in the sleep process and evaluate their pharmacokinetics and toxicity. The outcomes indicated that FX extended the length of sleep and reduced the time it took to fall asleep. When the combined treatment of FX and DZP showed synergistic sedative action. Also, FX had a binding affinity of −7.2 kcal/mol, while DZP showed −8.4 kcal/mol. The pharmacokinetic investigation of FX demonstrated favorable drug-likeness and strong pharmacokinetic characteristics. Ultimately, FX demonstrated a strong sedative impact in the mouse model, likely via interacting with the GABA_A receptor pathways.</p>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanovaccines: Immunogenic tumor antigens, targeted delivery, and combination therapy to enhance cancer immunotherapy","authors":"Zohreh Jahanafrooz,&nbsp;Fatemeh Oroojalian,&nbsp;Ahad Mokhtarzadeh,&nbsp;Abbas Rahdar,&nbsp;Ana M. Díez-Pascual","doi":"10.1002/ddr.22244","DOIUrl":"10.1002/ddr.22244","url":null,"abstract":"<p>Nanovaccines have been designed to overcome the limitations associated with conventional vaccines. Effective delivery methods such as engineered carriers or smart nanoparticles (NPs) are critical requisites for inducing self-tolerance and optimizing vaccine immunogenicity with minimum side effects. NPs can be used as adjuvants, immunogens, or nanocarriers to develop nanovaccines for efficient antigen delivery. Multiloaded nanovaccines carrying multiple tumor antigens along with immunostimulants can effectively increase immunity against tumor cells. They can be biologically engineered to boost interactions with dendritic cells and to allow a gradual and constant antigen release. Modifying NPs surface properties, using high-density lipoprotein-mimicking nanodiscs, and developing nano-based artificial antigen-presenting cells such as dendritic cell-derived-exosomes are amongst the new developed technologies to enhance antigen-presentation and immune reactions against tumor cells. The present review provides an overview on the different perspectives, improvements, and barriers of successful clinical application of current cancer therapeutic and vaccination options. The immunomodulatory effects of different types of nanovaccines and the nanoparticles incorporated into their structure are described. The advantages of using nanovaccines to prevent and treat common illnesses such as AIDS, malaria, cancer and tuberculosis are discussed. Further, potential paths to develop optimal cancer vaccines are described. Given the immunosuppressive characteristics of both cancer cells and the tumor microenvironment, applying immunomodulators and immune checkpoint inhibitors in combination with other conventional anticancer therapies are necessary to boost the effectiveness of the immune response.</p>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"99mTc-labeled, tofacitinib citrate encapsulated chitosan microspheres loaded in situ gel formulations for intra-articular treatment of rheumatoid arthritis","authors":"Merve Karpuz,&nbsp;Husniye Hande Aydin,&nbsp;Emre Ozgenc,&nbsp;Gulsah Erel-Akbaba,&nbsp;Evren Atlihan-Gundogdu,&nbsp;Zeynep Senyigit","doi":"10.1002/ddr.22247","DOIUrl":"10.1002/ddr.22247","url":null,"abstract":"<p>Inflammatory diseases including rheumatoid arthritis are major health problems. Although different techniques and drugs are clinically available for the diagnosis and therapy of the disease, novel approaches regarding radiolabeled drug delivery systems are researched. Hence, in the present study, it was aimed to design, prepare, and characterize ^99mTc-radiolabeled and tofacitinib citrate-encapsulated microsphere loaded poloxamer in situ gel formulations for the intra-articular treatment. Among nine different microsphere formulations, MS/TOFA-9 was chosen as the most proper one due to particle size, high encapsulation efficiency, and in vitro drug release behavior. Poloxamer 338 at a concentration of 15% was used to prepare in situ gel formulations. For intra-articular administration, microspheres were dispersed in an in situ gel containing 15% Poloxamer 338 and characterized in terms of gelation temperature, viscosity, rheological, mechanical, and spreadability properties. After the determination of the safe dose for MS/TOFA-9 and PLX-MS/TOFA-9 as 40 µL/mL in the cell culture study performed on healthy cells, the high anti-inflammatory effects were due to significant cellular inhibition of fibroblasts. In the radiolabeling studies with ^99mTc, the optimum radiolabeling condition was determined as 200 ppm SnCl₂ and 0.5 mg ascorbic acid, and both ^99mTc-MS/TOFA-9 and ^99mTc-PLX-MS/TOFA-9 exhibited high cellular binding capacity. In conclusion, although further in vivo experiments are required, PLX-MS/TOFA-9 was found to be a promising agent for intra-articular injection in rheumatoid arthritis.</p>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ddr.22247","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic effects of tilorone on mammary carcinogenesis through downregulation of pro-inflammatory cytokines and oxidative stress","authors":"Abu Sufiyan Chhipa,&nbsp;Ayush Sharma,&nbsp;Srashti Verma,&nbsp;Snehal S. Patel","doi":"10.1002/ddr.22246","DOIUrl":"10.1002/ddr.22246","url":null,"abstract":"<p>Tilorone dihydrochloride (tilorone) is an orally active interferon inducer with anticancer effects. The present study aimed to evaluate the anticancer effects of tilorone in breast cancer. MTT assay was done to measure the proliferation of MCF-7 and MDA-MB-231 breast cancer cells after treatment with tilorone. Mammary carcinogenesis was induced by subcutaneous injection (35 mg/kg, 0.5 mL) of dimethylbenz[<i>a</i>]anthracene (DMBA) in mammary pads of Sprague Dawley (SD) rats. Tumors were allowed to grow for 16 weeks till their sizes reached to 550–700 mm³, and then treated with 10 and 20 mg/kg of tilorone and standard drug doxorubicin (4 mg/kg) twice a week for 3 weeks. Normal and disease-control animals received normal saline. Tumor volumes and body weights were measured. Tumors were isolated to measure the levels of interferon-β (IFN-β), vascular endothelial growth factor-A (VEGF-A), P53 and inflammatory markers by enzyme-linked immunosorbent assay (ELISA). Serum biochemistry, lipid peroxidation (LPO) and antioxidant enzymes were measured by standard methods. Histopathology and immunohistochemistry (IHC) of P53 was done in tumor sections. Tilorone reduced the proliferation of MCF-7 and MDA-MB-231 cells with IC₅₀ concentrations at 34.08 µM and 14.27 µM, respectively. Tilorone treatment showed reduced tumor volume, and increased survival with no significant changes in the body weights. Tilorone treatment also decreased levels of inflammatory markers and VEGF-A and increased IFN-β and P53 levels. Further, treatment with tilorone also decreased LPO and increased antioxidants levels. Histopathology of tumor sections showed normalizing morphology of treated animals. IHC of tumor sections showed increased levels of P53. In conclusion, tilorone has potential anticancer effects against breast cancer.</p>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kynurenine pathway in type 2 diabetes: Role of metformin","authors":"Zainah Al-Qahtani,&nbsp;Hayder M. Al-kuraishy,&nbsp;Naif H. Ali,&nbsp;Yaser Hosny Ali Elewa,&nbsp;Gaber El-Saber Batiha","doi":"10.1002/ddr.22243","DOIUrl":"10.1002/ddr.22243","url":null,"abstract":"<p>The Kynurenine pathway (KP) which is involved in the synthesis of nicotinamide adenine dinucleotide (NAD) from tryptophan (Trp) is intricate in the development of insulin resistance (IR) and type 2 diabetes (T2D). Inflammatory reactions in response to cardiometabolic disorders can induce the development of IR through the augmentation of KP. However, kynurenine (KYN), a precursor of kynurenic acid (KA) is increased following physical exercise and involved in the reduction of IR. Consequently, KP metabolites KA and KYN have anti-diabetogenic effects while other metabolites have diabetogenic effects. KP modulators, either inhibitors or activators, affect glucose homeostasis and insulin sensitivity in T2D in a bidirectional way, either protective or detrimental, that is not related to the KP effect. However, metformin through inhibition of inflammatory signaling pathways can reduce the activation of KP in T2D. These findings indicated a strong controversy regarding the role of KP in T2D. Therefore, the objectives of this mini review were to clarify how KP induces the development of IR and T2D. In addition, this review aimed to find the mechanistic role of antidiabetic drug metformin on the KP, and how KP modulators affect the pathogenesis of T2D.</p>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, synthesis, molecular modeling, in vitro evaluation of novel piperidine-containing hydrazone derivatives as cholinesterase inhibitors","authors":"Fatih Tok,&nbsp;Nimet Baltaş,&nbsp;Burçin İrem Abas,&nbsp;Gizem Tatar Yılmaz,&nbsp;Süleyman Kaya,&nbsp;Bedia Koçyiğit-Kaymakçıoğlu,&nbsp;Özge Çevik","doi":"10.1002/ddr.22240","DOIUrl":"10.1002/ddr.22240","url":null,"abstract":"<p>In an effort to develop new and effective therapeutic agents for Alzheimer's disease, a series of hydrazone derivatives bearing piperidine rings have been designed and synthesized. The chemical structures of the compounds were characterized by various spectroscopic techniques. In vitro antioxidant and cholinesterase activities of the compounds were evaluated. Among the compounds, <b>N12</b> exhibited the most antioxidant activity in all methods (CUPRAC, FRAP, DPPH, ABTS). In vitro acetylcholinesterase (AChE) activity results of the compounds showed good IC₅₀ values between 14.124 ± 0.084 and 49.680 ± 0.110 µM were obtained (IC₅₀ = 38.842 ± 0.053 µM for Donepezil). Among the compounds, <b>N7</b> and <b>N6</b> are much more effective derivatives than the standard compound donepezil with IC₅₀ values of 14.124 ± 0.084 and 17.968 ± 0.072 µM, respectively. In vitro, butyrylcholinesterase (BChE) inhibition values of the compounds were between 13.505 ± 0.025 and 52.230 ± 0.027 μm. Among the compounds, <b>N6</b> has the highest BChE inhibition with an IC₅₀ value of 13.505 μm in the series. The cytotoxicity and AChE inhibitory activity of the compounds on SH-SY5Y cell lines were also evaluated. Kinetic studies were also performed to determine the behavior of the compounds as competitive or noncompetitive inhibitors. The binding modes of <b>N6</b>, which was determined to be highly effective according to in vitro analyses, with AChE and BChE were investigated using molecular docking studies, and the stability of the complexes was determined by molecular dynamics simulations. These findings indicated that AChE and BChE enzymes maintained their overall structural stability and compactness during interactions with compound <b>N6</b>.</p>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ddr.22240","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RETRACTION: “Dose-dependent Chemopreventive Effects of Citronellol in DMBA-Induced Breast Cancer Among Rats”","authors":"","doi":"10.1002/ddr.22238","DOIUrl":"10.1002/ddr.22238","url":null,"abstract":"<p><b>RETRACTION:</b> J. Rajendran, P. Pachaiappan and S. Subramaniyan, “Dose-dependent Chemopreventive Effects of Citronellol in DMBA-Induced Breast Cancer Among Rats,” <i>Drug Development Research</i> 80, no. 6 (2019): 867-876, https://doi.org/10.1002/ddr.21570.</p><p>The above article, published online on 16 July 2019 in Wiley Online Library (wileyonlinelibrary.com), and a corresponding Corrigendum, published on 10 June 2020 (https://doi.org/10.1002/ddr.21703), has been retracted by agreement between the journal Editor-in-Chief, Steven Fletcher; and Wiley Periodicals, LLC. The retraction has been agreed due to an overlap between images presented in Figure 3a and 3 f. Despite the previously produced Corrigendum, the overlap between Figure 3a and 3 f still remains. The authors were unable to provide a satisfactory explanation or provide an acceptable replacement for Figure 3 f. As a result, the editors have lost confidence in the results and conclusions presented in this study. The authors disagree with the retraction.</p>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ddr.22238","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}