RSC medicinal chemistry最新文献

{"title":"Navigating the complexities of drug development for metallo-β-lactamase inhibitors","authors":"Nakita Reddy, Alessandra Moraes Balieiro, José Rogério A. Silva, Christiaan A. Gouws, Awelani Mutshembele, Per I. Arvidsson, Hendrik G. Kruger, Thavendran Govender and Tricia Naicker","doi":"10.1039/D5MD00035A","DOIUrl":"10.1039/D5MD00035A","url":null,"abstract":"<p >The rising antibiotic resistance rates, especially among carbapenem-resistant Enterobacterales with metallo-β-lactamases (MBLs), highlight the urgent need for effective MBL inhibitors (MBLIs). Navigating the complexities of drug development for MBLIs requires addressing the significant challenges that have hindered its progress. Despite numerous efforts in pre-clinical development, the lack of standardized approaches has led to disparities, stalling the translation of potential MBLIs from research into clinical use. Alarmingly, there is only one metallo-β-lactamase inhibitory candidate in the pre-registration phase of development. This review highlights the need for a global consensus on key aspects of MBLI development, including standardized <em>in vitro</em> testing, refined animal models, harmonized toxicity assessments, consistent pharmacokinetic data, and uniform <em>in silico</em> methods. It also proposes solutions to these challenges, aiming to bridge the gap between research and clinical application.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" 8","pages":" 3393-3415"},"PeriodicalIF":3.6,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12159872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302812","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":"Lysine targeting covalent inhibitors of malarial kinase PfCLK3†","authors":"Skye B. Brettell, Gillian Cann, Abbey Begen, Saumya Sharma, Amit Mahindra, Lauren V. Carruthers, Graeme Milligan, David J. Clarke, Andrew B. Tobin and Andrew G. Jamieson","doi":"10.1039/D5MD00335K","DOIUrl":"10.1039/D5MD00335K","url":null,"abstract":"<p >Malaria continues to devastate tropical regions of the world, with resistance to frontline drugs on the rise. Kinase inhibition has emerged as a promising novel mechanism of action in the fight against malaria. We previously reported the development of TCMDC-135051 (<strong>1</strong>), a highly potent, multi-stage inhibitor of <em>Plasmodium falciparum</em> CLK3 (<em>Pf</em>CLK3). Building on this work, we subsequently developed the first covalent kinase inhibitor for malaria, selectively targeting a unique cysteine residue. Despite their high potency and selectivity, covalent inhibitors that target cysteine residues are particularly vulnerable to resistance arising from single point mutations of the nucleophilic residue. This work presents a novel strategy targeting the essential kinase catalytic lysine residue which has the potential to evade this resistance mechanism. Using structure based drug design, analogues of TCMDC-135051 (<strong>1</strong>) targeting Lys394 of <em>Pf</em>CLK3 were developed. Four compounds, all harbouring benzaldehyde-based warheads, covalently engaged Lys394 as determined by protein mass spectrometry. These analogues were highly potent against recombinant protein, with good parasiticidal potency and cytotoxicity profiles. These molecules <strong>4</strong>, <strong>5</strong>, <strong>8</strong>, <strong>9</strong> are the first lysine-targeting covalent inhibitors reported for malaria and offer a promising general strategy for future antimalarial drug discovery.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" 8","pages":" 3530-3540"},"PeriodicalIF":3.6,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12164071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302811","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":"New ionizable lipids for non-viral mRNA delivery with secondary amine cyclic ether head groups†","authors":"Eric L. Dane, Aditya R. Pote, Martin Hemmerling, Werngard Czechtizky, Liping Zhou and Annette Bak","doi":"10.1039/D5MD00115C","DOIUrl":"10.1039/D5MD00115C","url":null,"abstract":"<p >Lipid nanoparticles (LNPs) are the most widely used non-viral delivery approach for messenger ribonucleic acid (mRNA). Among the different components in an LNP, the ionizable lipid plays critical roles in interacting with the mRNA cargo and facilitating delivery to the cytosol, as well as influencing the LNP's tissue tropism <em>via</em> the protein corona. To date the most successful ionizable lipids have relied on a tertiary amine head group as the site of protonation. We hypothesized that potent ionizable lipids based on a secondary amine could be discovered using a design, make, test and analyze (DMTA) cycle approach. Starting from a lead lipid with a secondary amine cyclic ether head group, we optimized delivery efficiency by systematically modifying the lipid linker length, tail symmetry, tail branching pattern, and head group structure. The mRNA-LNPs formulated with these lipids were evaluated <em>in vivo</em> by quantifying liver protein expression. Using this rational lipid design strategy, we identified many candidates that outperformed the benchmark lipid (MC3), supporting the further development of this ionizable lipid class. Notably, several structure activity relationships (SARs) that highlight how sensitive ionizable lipid activity is to relatively minor structural changes are reported.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" 7","pages":" 3273-3280"},"PeriodicalIF":4.1,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144174780","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 and antitumor activity evaluation of novel IMPDH II and HDAC1 dual inhibitor†","authors":"Fang-Bo Deng, Hong-Wei Jia, De-Xiang Hu, Zhen-Li Li, Xiao-Meng Xiu, Xue-Qi Zhao, Yang Liu, Hua-Li Yang and Maosheng Cheng","doi":"10.1039/D5MD00007F","DOIUrl":"10.1039/D5MD00007F","url":null,"abstract":"<p >The development of multi-target inhibitors has garnered considerable attention in the field of cancer therapy. We have designed and synthesized a total of 80 derivatives, categorized into <strong>A</strong>, <strong>B</strong>, and <strong>C</strong> series. Among these compounds, <strong>C12</strong> (<em>h</em>IMPDH II, IC<small>₅₀</small> = 84.69 ± 0.83 nM; HDAC1, IC<small>₅₀</small> = 81.75 ± 0.82 nM) and <strong>C18</strong> (<em>h</em>IMPDH II, IC<small>₅₀</small> = 820.50 ± 1.41 nM; HDAC1, IC<small>₅₀</small> = 131.90 ± 1.02 nM) exhibited promising inhibitory activity against <em>h</em>IMPDH II and HDAC1. Compared to the IMPDH-positive compound MPA (IC<small>₅₀</small> = 403.23 ± 2.92 nM) and the HDAC-positive compound SAHA (IC<small>₅₀</small> = 1165.72 ± 1.22 nM), compound <strong>C12</strong> (IC<small>₅₀</small> value of 305.31 ± 0.67 nM) demonstrated superior anti-proliferative activity against K-562 cells <em>in vitro</em>. Compound <strong>C12</strong> exhibited good liver microsomal stability with a moderate half-life (<em>T</em><small>_1/2</small>). Furthermore, compound <strong>C12</strong> exhibited acceptable <em>in vivo</em> pharmacokinetics of properties. In conclusion, compound <strong>C12</strong> represents a potential new dual inhibitor targeting both <em>h</em>IMPDH II and HDAC1.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" 7","pages":" 3084-3107"},"PeriodicalIF":4.1,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128533","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":"Beta-cyclodextrin formulation of a disulfide-bond disrupting agent for improved systemic exposure†","authors":"Zaafir M. Dulloo, Ion Ghiviriga, Mary E. Law, Sarvesh K. Verma, Abhisheak Sharma, Brian K. Law and Ronald K. Castellano","doi":"10.1039/D5MD00334B","DOIUrl":"10.1039/D5MD00334B","url":null,"abstract":"<p >Disulfide-bond disrupting agents (DDAs) are a class of cyclic thiosulfonates that have been shown to kill human epidermal growth factor receptor (HER) family-overexpressing breast cancer (BC) cells selectively and with no adverse side effects. Previous structure–activity relationships suggested a strong correlation between DDA lipophilicity and potency. In this study, we present the use of cyclodextrins (CDs) as molecular excipients to address the possible solubilizing drawback of increasingly lipophilic DDAs in oral administrations. The formulation of tcyDTDO, a potent second-generation DDA, with beta-cyclodextrin (BCD) and 2-hydroxypropyl-beta-cyclodextrin (HPB) was investigated. The choice of BCD as an optimal host over other CDs was guided by two <em>in silico</em> methods, namely: (1) host cavity volume estimations using a computational modeling approach and (2) binding energy (BE) calculations from simulations of different complexation geometries. A solid-state inclusion complex (IC) between tcyDTDO and BCD was prepared by kneading. Characterization by ATR-FTIR revealed positioning of tcyDTDO inside the cavity of BCD. Phase-solubility plots were constructed using NMR spectroscopy to measure the concentrations of host and guest in solution; a powerful technique that has yet to be exploited in the context of host–guest chemistry. The <em>A</em><small>_L</small>-type plots obtained pointed to the formation of 1 : 1 complexes with both BCD and HPB. BCD formed a stronger complex with tcyDTDO (<em>K</em><small>_a</small> of 4090 M<small>⁻¹</small>) although the solubility of tcyDTDO was enhanced by only 3-fold from an intrinsic solubility of 1.58 mM. Contrastingly, HPB displayed a lower affinity for tcyDTDO (<em>K</em><small>_a</small> of 81 M<small>⁻¹</small>) but resulted in a remarkable 90-fold increase in solubility with tcyDTDO concentrations approaching 150 mM. Encapsulation of tcyDTDO in both cases did not hinder its anti-cancer activity as they retained cytotoxicity against MDA-MB-468 (EGFR+) BC cells <em>in vitro</em>. More striking was the superior pharmacokinetic profile and systemic exposure of tcyDTDO observed in male Sprague-Dawley rats when formulated with BCD as indicated by an area under the concentration <em>vs.</em> time curve (AUC<small>_0–24</small>) of 3150 ± 381 ng h mL<small>⁻¹</small>. This work suggests a correlation between <em>K</em><small>_a</small> and <em>in vivo</em> pharmacokinetics of DDAs following their complexation with CDs and provides an ameliorated approach for their oral administration in future animal studies.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" 8","pages":" 3622-3632"},"PeriodicalIF":3.6,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12124217/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199958","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":"Rational design of indolyl acrylamides as antibacterial agents targeting multidrug-resistant Acinetobacter baumannii strains†","authors":"Velvett G. Domínguez-Méndez, Rosa María Chávez-Santos, Karol Carrillo-Jaimes, Alejandra Hernández-Santoyo, Santos Ramírez-Carreto, Armando Hernandez-Garcia, Rodrigo Aguayo-Ortiz, Corina-Diana Ceapă, José Rivera-Chavéz and Roberto Martínez","doi":"10.1039/D5MD00145E","DOIUrl":"10.1039/D5MD00145E","url":null,"abstract":"<p >Antimicrobial resistance (AMR) has become a significant public health problem. This study investigated the structure–activity relationship of indole core molecules to uncover novel antimicrobials against resistant bacteria. Their antimicrobial evaluation against ESKAPEE bacteria showed superior efficacy compared to cefepime, meropenem, ciprofloxacin, and gentamicin against multidrug-resistant <em>A. baumannii</em> strain A-564, with minimum inhibitory concentration (MIC) values of 4.3 and 1.2 μg mL<small>⁻¹</small> for compounds <strong>12e</strong> and <strong>12j</strong>, respectively. Also, the same compounds showed better activity than cefepime for <em>A. baumannii</em> BAA ATCC 747 with MIC values of 1.2 and 4.4 μg mL<small>⁻¹</small>. In addition, <strong>12e</strong> and <strong>12f</strong> showed activity against methicillin- and penicillin-resistant <em>S. aureus</em> with MIC values of 3.2 and 2.1 μg mL<small>⁻¹</small>. Furthermore, the highly active compounds <strong>12e</strong> and <strong>12j</strong> exhibited low toxicity, with hemolysis values &gt;40 μg mL<small>⁻¹</small>. Preliminary examination of the mechanism of action revealed that <strong>12e</strong> could exhibit dose-dependent inhibition of the <em>Ab</em>FtsZ<small>_1–412</small> enzyme from strain XDR A-564, achieving 51% inhibition of GTPase activity at 32 μg mL<small>⁻¹</small>, thus altering the binary fission process, which could be attributed to the fact that <strong>12e</strong> binds to the GTP site and interferes with the function of the enzyme by inhibiting the formation of the Z-ring. Also, a cell viability assay indicates that cells treated with these compounds showed increased permeability, compromising the stability of the <em>A. baumannii</em> A-564 membrane. These results provided valuable information for further developing indolyl-acrylamides as new antimicrobial agents.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" 8","pages":" 3567-3581"},"PeriodicalIF":3.6,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12143416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249443","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":"NLRP3 inflammasome: structure, mechanism, drug-induced organ toxicity, therapeutic strategies, and future perspectives","authors":"Desh Deepak Singh","doi":"10.1039/D5MD00167F","DOIUrl":"10.1039/D5MD00167F","url":null,"abstract":"<p >Drug-induced toxicity is an important issue in clinical medicine, which typically results in organ dysfunction and adverse health consequences. The family of NOD-like receptors (NLRs) includes intracellular proteins involved in recognizing pathogens and triggering innate immune responses, including the activation of the NLRP3 inflammasome. The NLRP3 (nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 3) inflammasome is a critical component for both innate and adaptive immune responses and has been implicated in various drug-induced toxicities, including hepatic, renal, and cardiovascular diseases. The unusual activation of the NLRP3 inflammasome causes the release of pro-inflammatory cytokines, such as IL-1β and IL-18, which can lead to more damage to tissues. Targeting NLRP3 inflammasome is a potential therapeutic endeavour for suppressing drug-induced toxicity. This review provides insights into the mechanism, drug-induced organ toxicity, therapeutic strategies, and prospective therapeutic approaches of the NLRP3 inflammasome and summarizes the developing therapies that target the inflammasome unit. This review has taken up one of the foremost endeavours in understanding and inhibiting the NLRP3 inflammasome as a means of generating safer pharmacological therapies.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" 7","pages":" 2937-2957"},"PeriodicalIF":4.1,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080065","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":"Development and clinical potential of 18F-PSiMA for prostate cancer PET imaging†","authors":"Lexi Gower-Fry, Justin J. Bailey, Melinda Wuest, Susan Pike, Alexey Kostikov, Andreas Dorian, Carmen Wängler, Frank Wuest and Ralf Schirrmacher","doi":"10.1039/D5MD00275C","DOIUrl":"10.1039/D5MD00275C","url":null,"abstract":"<p >Prostate-specific membrane antigen (PSMA) is a key target for diagnosing prostate cancer through positron emission tomography (PET). While <small>⁶⁸</small>Ga-labeled PSMA compounds are widely used, <small>¹⁸</small>F-labeled PSMA inhibitors have gained traction for clinical tumor imaging. We previously investigated PSMA-targeting compounds based on the Lys-urea-Glu motif, incorporating a silicon fluoride-acceptor (SiFA) and chemical auxiliaries to enhance <em>in vivo</em> biodistribution. This led to the development of <small>¹⁸</small>F-PSiMA, a SiFA-based radiotracer with an optimized linker exhibiting favorable PSMA potency (IC<small>₅₀</small> = 154 ± 47 nM in LNCaP cells). <small>¹⁸</small>F-PSiMA radiosynthesis with low to high concentrations of <small>¹⁸</small>F and precursor achieved molar activities (<em>A</em><small>_m</small>) of 10.9–82.5 GBq μmol<small>⁻¹</small> and showed a 24–38% increase in tumor uptake in LNCaP tumors (SUV<small>_60min</small> 1.56 ± 0.18; 7.23 ± 0.75% ID per g at lower <em>A</em><small>_m</small> and SUV<small>_60min</small> 1.90 ± 0.29; 9.62 ± 1.29% ID per g at higher <em>A</em><small>_m</small>) compared to our previous lead, <small>¹⁸</small>F-SiFA-Asp<small>₂</small>-PEG<small>₃</small>-PSMA. PSMA specificity was confirmed by a 20 ± 10% reduction in SUV<small>_60min</small> upon co-injection with DCFPyl. These promising <em>in vitro</em> and <em>in vivo</em> results support further clinical translation of <small>¹⁸</small>F-PSiMA for prostate cancer PET imaging.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" 8","pages":" 3633-3644"},"PeriodicalIF":3.6,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12127850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216799","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":"Design, synthesis and biological studies of carbazole–thiosemicarbazone hybrids as potential topoisomerase II catalytic inhibitors†","authors":"PengHui Li, LiJun Xie, ShiYan Feng, XuDong Xiang, ChunXia Chen and LiangXiong Xu","doi":"10.1039/D5MD00234F","DOIUrl":"10.1039/D5MD00234F","url":null,"abstract":"<p >In this study, carbazole–thiosemicarbazone hybrids were designed, synthesized and investigated for their topoisomerase II (Topo II) inhibition and antiproliferative activity. Results showed that compounds <strong>C1</strong> and <strong>C3</strong> could significantly inhibit the activity of Topo II at 10 μM. Meanwhile, mechanism studies revealed that these hybrids act as non-intercalative Topo II catalytic inhibitors. Additionally, molecular docking revealed the promising binding of the investigated members toward Topo II, with the potential to occupy the ATPase domain. Interestingly, these hybrids exhibited strong antiproliferative activity against HeLa, A549, LNCaP, and MG63 cancer cell lines. Furthermore, compounds <strong>C1</strong> and <strong>C3</strong> could significantly induce apoptosis and inhibit the migration and clonogenic survival of MG63 cells.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" 7","pages":" 3312-3320"},"PeriodicalIF":4.1,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144174777","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":"Revisiting the role of steroidal therapeutics in the 21st century: an update on FDA approved steroidal drugs (2000–2024)","authors":"Ranjit Singh and Ranju Bansal","doi":"10.1039/D5MD00027K","DOIUrl":"10.1039/D5MD00027K","url":null,"abstract":"<p >Steroids are biologically active polycyclic compounds that have garnered significant scientific attention due to their distinct physiochemical properties and diverse medical applications. Since their invention more than 90 years ago, steroids have remained the most important and necessary class of regulatory molecules in the evolution process of living creatures and have fascinated scientists due to their broad-spectrum biological activities. Over time, scientific innovations and expanded understanding of mechanisms related to diversified biological activities of steroids have made them cheaper, efficient and more specific therapeutic agents which could be effective in the prevention and cure of numerous diseases like cancer, inflammation, asthma, microbial infection, and many more. However, steroidal drugs remain a double-edged sword having significant therapeutic benefits but with incidence of several adverse effects if used for a longer duration and/or with incorrect dose. Nevertheless, novel treatment approaches such as nanoparticles or liposomal drug delivery, real-time monitoring and the use of artificial intelligence in steroidal therapy outweigh their risk factors and provide an effective and safe treatment with minimum adverse effects. Furthermore, the repurposing of steroids in different diseases, <em>e.g.</em> successful use of dexamethasone or hydrocortisone during COVID-19 pandemic has renewed the interest in steroidal therapeutics. The present review provides an update on FDA approved steroidal drugs during the years 2000–2024, the status of their clinical studies, the challenges offered by steroidal therapy and the future perspectives to counterbalance all these challenges. Moreover, this review also delivers useful data on the repurposing of steroidal drugs against various diseases along with the novel techniques used for improved steroid delivery.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" 7","pages":" 2902-2918"},"PeriodicalIF":4.1,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144022255","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}