RSC medicinal chemistry最新文献

{"title":"Antibacterial activity of the structurally novel C-2 amine-substituted analogues based on quinoxaline†","authors":"Yuting Liu, Pengju Yang, Yunyun Zhou and Zhiwen Zhou","doi":"10.1039/D4MD00670D","DOIUrl":"10.1039/D4MD00670D","url":null,"abstract":"<p >In the current study, we have designed and prepared a series of quinoxaline-based compounds, which were derived from <em>o</em>-phenylenediamine. Among them, compounds <strong>5m–5p</strong> displayed good to moderate antibacterial activity with MICs of 4–16 μg mL<small>⁻¹</small> against <em>S. aureus</em>, 8–32 μg mL<small>⁻¹</small> against <em>B. subtilis</em>, 8–32 μg mL<small>⁻¹</small> against MRSA and 4–32 μg mL<small>⁻¹</small> against <em>E. coli</em>, respectively. Compound <strong>5p</strong>, identified as a potent broad-spectrum antibacterial agent, demonstrated the strongest inhibitory effects against a range of bacterial strains and low cytotoxicity, thereby warranting further investigation. Compound <strong>5p</strong> not only demonstrated the ability to disperse established bacterial biofilms but also induced a slower development of bacterial resistance compared to norfloxacin. Moreover, bactericidal time-kill kinetic studies revealed that at a high concentration of 3MIC, compound <strong>5p</strong> was capable of directly killing MRSA cells. The subsequent postcontact effect (PCE) results showed that the growth rate of viable bacteria (MRSA) was greatly impacted and did not recover in less than 24 hours, even after antibacterial agent <strong>5p</strong> was removed. The drug-like properties and ADME prediction exhibited that <strong>5m–5p</strong> obeyed Lipinski's rule of five and therefore presumably maintained moderate to good bioavailability and human intestinal absorption rate when administered orally. Mechanistic investigations have elucidated that compound <strong>5p</strong> exerted its antibacterial effect by compromising the structural integrity of bacterial cell membranes, resulting in the leakage of intracellular constituents and ultimately causing bacterial demise. Further studies <em>in vivo</em> have demonstrated that <strong>5p</strong> exhibited potent antibacterial efficacy against MRSA in murine corneal infection models, particularly at elevated concentrations. The current dataset has also been meticulously analyzed to delineate the structure–activity relationships (SARs) of the synthesized compounds.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" 2","pages":" 812-825"},"PeriodicalIF":4.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142688706","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 and synthesis of (E)-3-benzylideneindolin-2-one derivatives as potential allosteric inhibitors of Aurora A kinase†","authors":"YongLai Jiao, Jie Zhong, JinFang Xu, ShaoBo Ning, TaiGang Liang, MingZhu Zhao and Jian Zhang","doi":"10.1039/D4MD00373J","DOIUrl":"10.1039/D4MD00373J","url":null,"abstract":"<p >The mitotic kinase Aurora A, a pivotal regulator of the cell cycle, is overexpressed in various cancers and has emerged as one of the most promising targets for anticancer drug discovery. However, the lack of specificity and potential toxicity have impeded clinical trials involving orthosteric inhibitors. In this study, allosteric sites of Aurora A were predicted using the AlloReverse web server. Based on the non-ATP competitive inhibitor Tripolin A and molecular docking information targeting the desired allosteric site 3 of Aurora A, a series of (<em>E</em>)-3-benzylideneindolin-2-one derivatives were designed and synthesized. Compared to Tripolin A, our compounds <strong>AK09</strong>, <strong>AK34</strong> and <strong>AK35</strong> have stronger inhibitory effects and can be further investigated as potential allosteric inhibitors. Moreover, the compound <strong>AK34</strong> with the strongest inhibitory activity (IC<small>₅₀</small> = 1.68 μM) has a high affinity for Aurora A (<em>K</em><small>_D</small> = 216 nM). According to the analysis of the structure–activity relationship of the compounds and the results of their molecular docking models, these compounds tend to act on the allosteric site 3 of Aurora A.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" 2","pages":" 826-834"},"PeriodicalIF":4.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710774","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":"Synthesis and antifungal evaluation of new azole derivatives containing 1,2,3-triazole†","authors":"Zhengxiao Huang, Hongjie Chen, Xiao Zhang, Ruirui Wang, Chunyan Hu and Zewei Mao","doi":"10.1039/D4MD00724G","DOIUrl":"10.1039/D4MD00724G","url":null,"abstract":"<p >Invasive fungal infections caused by <em>C. albicans</em> are becoming increasingly serious and there is an urgent need for exploring new antifungal drugs. In the present work, a series of new azole derivatives containing a 1,2,3-triazole moiety have been prepared, and <em>in vitro</em> antifungal activity have been evaluated. The results revealed that most compounds showed excellent antifungal activity against <em>C. albicans</em> SC5314 and drug-resistant SC5314-FR. In particular, compounds <strong>4h</strong>, <strong>4j</strong>, <strong>4l</strong>, <strong>4s</strong> and <strong>4w</strong> exhibited better antifungal activity than FLC. The preliminary mechanism study indicated that <strong>4s</strong> could damage the integrity of the cell structure, increase the permeability of the cell membrane, and cause the leakage of cell contents of <em>C. albicans</em>. The molecular docking study indicated that <strong>4s</strong> showed an obvious binding site with the target CYP51 (PDB ID: 5TL8). Therefore, <strong>4s</strong> could be considered as a new antifungal agent targeting CYP51 for further study.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" 2","pages":" 791-800"},"PeriodicalIF":4.1,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142627402","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":"Amides of moronic acid and morolic acid with the tripeptides MAG and GAM targeting antimicrobial, antiviral and cytotoxic effects†","authors":"Uladzimir Bildziukevich, Lucie Černá, Jana Trylčová, Marie Kvasnicová, Lucie Rárová, David Šaman, Petra Lovecká, Jan Weber and Zdeněk Wimmer","doi":"10.1039/D4MD00742E","DOIUrl":"10.1039/D4MD00742E","url":null,"abstract":"<p >A series of amides of selected plant triterpenoids, moronic acid and morolic acid, with the tripeptides MAG and GAM, was designed and synthesized. Two required tripeptides <strong>5</strong> and <strong>10</strong> were synthesized by a step-wise chain elongation of the ethyl esters of either glycine or <small>L</small>-methionine at their N-terminus using Boc-protected amino acids in each step. The tripeptides <strong>5</strong> and <strong>10</strong> were used for the synthesis of <strong>13–23</strong>, the derivatives of moronic acid (<strong>11</strong>) and morolic acid (<strong>12</strong>), to get a series of amide derivatives of the less frequently studied triterpenoids <strong>11</strong> and <strong>12</strong>. The target compounds, and their intermediates, were subjected to an investigation of their antimicrobial, antiviral and cytotoxic activity. Selectivity of the pharmacological effects was found. Generally, the target compounds inhibited only the G<small>⁺</small> microorganisms. Compound <strong>16</strong> inhibited <em>Staphylococcus aureus</em> (<em>I</em> = 99.6%; <em>c</em> = 62.5 μM) and <em>Enterococcus faecalis</em> (<em>I</em> = 85%; <em>c</em> = 250 μM). Several compounds showed moderate antiviral effects, both anti-HIV-1, <strong>19</strong> (EC<small>₅₀</small> = 57.0 ± 4.1 μM, CC<small>₅₀</small> &gt; 100 μM), <strong>20</strong> (EC<small>₅₀</small> = 17.8 ± 2.1 μM, CC<small>₅₀</small> = 41.0 ± 5.2 μM) and <strong>23</strong> (EC<small>₅₀</small> = 12.6 ± 0.82 μM, CC<small>₅₀</small> = 38.0 ± 4.2 μM), and anti-HSV-1, <strong>22</strong> (EC<small>₅₀</small> = 27.7 ± 3.5 μM, CC<small>₅₀</small> &gt; 100 μM) and <strong>23</strong> (EC<small>₅₀</small> = 30.9 ± 3.3 μM, CC<small>₅₀</small> &gt; 100 μM). The target compounds showed no cytotoxicity in cancer cells, however, several of their intermediates were cytotoxic. Compound <strong>21</strong> showed cytotoxicity in HeLa (IC<small>₅₀</small> = 7.9 ± 2.1 μM), G-361 (IC<small>₅₀</small> = 8.0 ± 0.6 μM) and MCF7 (IC<small>₅₀</small> = 8.6 ± 0.2 μM) cancer cell lines, while being non-toxic in normal fibroblasts (BJ; IC<small>₅₀</small> &gt; 50 μM).</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" 2","pages":" 801-811"},"PeriodicalIF":4.1,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11575580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682721","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":"meso-Substituted AB3-type phenothiazinyl porphyrins and their indium and zinc complexes photosensitising properties, cytotoxicity and phototoxicity on ovarian cancer cells†","authors":"Brém Balázs, Bianca Stoean (Vasile), Éva Molnár, Eva Fischer-Fodor, Ovidiu Bălăcescu, Raluca Borlan, Monica Focsan, Adriana Grozav, Patriciu Achimaş-Cadariu, Emese Gál and Luiza Gaina","doi":"10.1039/D4MD00601A","DOIUrl":"10.1039/D4MD00601A","url":null,"abstract":"<p >New <em>meso</em>-substituted AB<small>₃</small>-type phenothiazinyl porphyrins and ferrocenylvinyl phenothiazinyl porphyrin were synthesised by Suzuki–Miyaura and Mizoroki–Heck cross-coupling reactions, respectively. The free porphyrins were further used in the synthesis of new indium(<small>III</small>) or zinc(<small>II</small>) porphyrin complexes. All porphyrins exhibit red fluorescence emission in solution, a property that remains unimpaired following internalisation in ovarian A2780 cancer cells, as evidenced by fluorescence microscopy images. The In(<small>III</small>) phenothiazinyl porphyrin complexes show a higher quantum yield of fluorescence emission (<strong>2a</strong><em>Φ</em><small>_F</small> = 30%, <strong>4a</strong><em>Φ</em><small>_F</small> = 29%, <strong>5a</strong><em>Φ</em><small>_F</small> = 28%) compared to the free base porphyrin precursors, or Zn(<small>II</small>) complex <strong>4b</strong> (<em>Φ</em><small>_F</small> = 10%). The potential of novel phenothiazinyl porphyrins to act as photosensitisers was evaluated using two distinct approaches. The first was through the measurement of the singlet oxygen quantum yield <em>Φ</em><small>_Δ</small>(<small>¹</small>O<small>₂</small>), while the second employed <em>in vitro</em> measurements of metabolic activity, oxidative stress, nuclear factor-erythroid 2 related factor 2 (Nrf-2) activation and tumour necrosis factor-alpha (TNF-α) under both dark and light irradiation conditions. As reflected by the IC<small>₅₀</small> values, the most potent cytotoxicity of the phenothiazinyl porphyrins against the A2780 cells was observed for In(<small>III</small>) ferrocenylvinyl phenothiazinyl porphyrin <strong>4a</strong> (36.38 μM), the remaining compounds are less cytotoxic. The reduction in metabolic activity was observed in A2780 ovarian tumour cells treated with <strong>4a</strong> and <strong>6a</strong> and exposed to light compared to treatment in the absence of light. The oxidative stress, TNF-α and Nrf-2 transcription factor were particularly notable when A2780 cells were treated with <strong>4a</strong> and subsequently photoirradiated, the oxidative stress was linked to the highest value of <em>Φ</em><small>_Δ</small>(<small>¹</small>O<small>₂</small>) recorded for <strong>4a</strong> (60%).</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" 2","pages":" 747-766"},"PeriodicalIF":4.1,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11575637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682720","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":"Human microbiome derived synthetic antimicrobial peptides with activity against Gram-negative, Gram-positive, and antibiotic resistant bacteria†","authors":"Walaa K. Mousa, Ashif Y. Shaikh, Rose Ghemrawi, Mohammed Aldulaimi, Aya Al Ali, Nour Sammani, Mostafa Khair, Mohamed I. Helal, Farah Al-Marzooq and Emilia Oueis","doi":"10.1039/D4MD00383G","DOIUrl":"10.1039/D4MD00383G","url":null,"abstract":"<p >The prevalence of antibacterial resistance has become one of the major health threats of modern times, requiring the development of novel antibacterials. Antimicrobial peptides are a promising source of antibiotic candidates, mostly requiring further optimization to enhance druggability. In this study, a series of new antimicrobial peptides derived from lactomodulin, a human microbiome natural peptide, was designed, synthesized, and biologically evaluated. Within the most active region of the parent peptide, linear peptide <strong>LM6</strong> with the sequence LSKISGGIGPLVIPV-NH<small>₂</small> and its cyclic derivatives <strong>LM13a</strong> and <strong>LM13b</strong> showed strong antibacterial activity against Gram-positive bacteria, including resistant strains, and Gram-negative bacteria. The peptides were found to have a rapid onset of bactericidal activity and transmission electron microscopy clearly shows the disintegration of the cell membrane, suggesting a membrane-targeting mode of action.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" 1","pages":" 312-323"},"PeriodicalIF":4.1,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11520653/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547112","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":"Light enhanced cytotoxicity and antitumoral effect of a ruthenium-based photosensitizer inspired from natural alkaloids†","authors":"Gennaro Sanità, Maria Laura Alfieri, Barbara Carrese, Serena Damian, Vincenza Mele, Gaetano Calì, Brigida Silvestri, Sebastiano Marra, Susan Mohammadi, Giuseppina Luciani, Paola Manini and Annalisa Lamberti","doi":"10.1039/D4MD00600C","DOIUrl":"10.1039/D4MD00600C","url":null,"abstract":"<p >In this work, we report on the synthesis and properties of a new sensitizer for photodynamic therapy applications, constituted by a ruthenium(<small>II</small>) complex (<strong>1</strong>) featuring a ligand inspired from natural isoquinoline alkaloids. The spectroscopic analysis revealed that <strong>1</strong> is characterized by an intense red emission (<em>λ</em><small>_em</small> = 620 nm, <em>Φ</em> = 0.17) when excited at 550 nm, a low energy radiation warranting for a safe therapeutic approach. The phototoxicity of <strong>1</strong> on human breast cancer (Hs578T) and melanoma (A375) cell lines was assessed after irradiation using a LED lamp (525 nm, total fluence 10 J cm<small>⁻²</small>). <em>In vitro</em> biological assays indicated that the cytotoxicity of <strong>1</strong> was significantly enhanced by light reaching IC<small>₅₀</small> values below the micromolar threshold. The cell damage induced by <strong>1</strong> proved to be strictly connected with the overproduction of reactive oxygen species (ROS) responsible for mitochondrial dysfunction leading to the activation of caspases and then to apoptosis, and for DNA photocleavage leading to cell cycle arrest.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" 2","pages":" 779-790"},"PeriodicalIF":4.1,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11565246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648594","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":"Correction: Anti-schistosomal activity and ADMET properties of 1,2,5-oxadiazinane-containing compound synthesized by visible-light photoredox catalysis","authors":"Kennosuke Itoh, Hiroki Nakahara, Atsushi Takashino, Aya Hara, Akiho Katsuno, Yuriko Abe, Takaaki Mizuguchi, Fumika Karaki, Shigeto Hirayama, Kenichiro Nagai, Reiko Seki, Noriko Sato, Kazuki Okuyama, Masashi Hashimoto, Ken Tokunaga, Hitoshi Ishida, Fusako Mikami, Kofi Dadzie Kwofie, Hayato Kawada, Bangzhong Lin, Kazuto Nunomura, Toshio Kanai, Takeshi Hatta, Naotoshi Tsuji, Junichi Haruta and Hideaki Fujii","doi":"10.1039/D4MD90044H","DOIUrl":"10.1039/D4MD90044H","url":null,"abstract":"<p >Correction for ‘Anti-schistosomal activity and ADMET properties of 1,2,5-oxadiazinane-containing compound synthesized by visible-light photoredox catalysis’ by Kennosuke Itoh <em>et al.</em>, <em>RSC Med. Chem.</em>, 2024, https://doi.org/10.1039/d4md00599f.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" 12","pages":" 4222-4222"},"PeriodicalIF":4.1,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11500060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142507034","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 and synthesis of coumarin-based amphoteric antimicrobials with biofilm interference and immunoregulation effects.","authors":"Qun Tang, Haiyang Zhang, Kasemsiri Chandarajoti, Zirui Jiao, Lianhua Nie, Sai Lv, Jiakun Zuo, Wen Zhou, Xiangan Han","doi":"10.1039/d4md00721b","DOIUrl":"10.1039/d4md00721b","url":null,"abstract":"<p><p>Bacterial infections pose a threat to human and animal health, and the formation of biofilm exacerbates the microbial threat. New antimicrobial agents to address this challenge are much needed. In this study, several new amphoteric compounds derived from the natural product coumarin were designed and synthesized by mimicking the structure and function of antimicrobial peptides. Strong inhibitory effect of 8b was observed on <i>S. aureus</i> 29213 and five isolated clinically positive strains, with an MIC value of 1-4 μg mL^-1, accompanied by the potential advantages of rapid sterilization and no drug resistance. The <i>in vivo</i> activity of 8b was supported by good antibacterial and anti-inflammatory effects in a mouse wound infection model. More importantly, good immunomodulatory effects, inhibition of biofilm formation, and biofilm clearance were detected in the treatment using 8b, which makes it a potential candidate antibacterial for controlling <i>S. aureus</i> infections forming biofilm.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11712211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971994","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":"Technical, preclinical, and clinical developments of Fc-glycan-specific antibody–drug conjugates","authors":"Qiang Yang and Yunpeng Liu","doi":"10.1039/D4MD00637B","DOIUrl":"10.1039/D4MD00637B","url":null,"abstract":"<p >Antibody–drug conjugates (ADCs) have emerged as a powerful avenue in the therapeutic treatment of cancer. Site-specific antibody–drug conjugations represent the latest trend in the development of ADCs, addressing the limitations of traditional random conjugation technologies. This article summarizes the innovative development of Fc-glycan-specific ADCs (gsADCs), which utilize the conserved Fc <em>N</em>-glycan as the anchor point for site-specific conjugation. This approach offers significant strengths, including improved ADC homogeneity and overall hydrophilicity, enhanced pharmacokinetics and therapeutic index, and potentially reduced Fc receptor-mediated side effects. Currently dozens of gsADCs are in different preclinical and clinical development stages. Notably, JSKN003 and IBI343 have demonstrated promising results in phase 1 trials and are advancing into phase 3 studies. This review discusses the advantages of Fc-glycan-conjugation, various glycan-specific conjugation techniques, and the preclinical and clinical development of gsADCs. While challenges such as increased manufacturing cost for large-scale production need continuous innovation to overcome and there are different opinions regarding the pros and cons of reduced/diminished affinities to Fc gamma receptors, ongoing research and clinical progress underscore the potential of gsADCs to renovate ADC cancer therapy.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" 1","pages":" 50-62"},"PeriodicalIF":4.1,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11575643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682724","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}