ACS Bio & Med Chem Au最新文献

{"title":"High Drug Encapsulation Capacity in Cyclodextrin-Based Nanoparticles: Characterization and <i>In Vivo</i> Antitumor Efficacy in Tumor-Bearing Mice.","authors":"Tomoki Kosugi, Mina Sakuragi, Madoka Toya, Tomoki Nishimura, Taiki Saito, Reina Kobayashi, Liliana de Campo, Kazuo Sakurai, Riku Kawasaki, Noriko Miyamoto","doi":"10.1021/acsbiomedchemau.5c00220","DOIUrl":"10.1021/acsbiomedchemau.5c00220","url":null,"abstract":"<p><p>Insufficient drug encapsulation, typically at about 10 wt %, remains a major challenge in the design of nanotechnology-based drug delivery systems. In this study, we created cyclodextrin-based nanoparticles (CDNP_PEGs), synthesized by the hyperbranched polymerization of cyclodextrins using a diepoxy poly-(ethylene glycol) linker, which exhibited a high drug encapsulation capacity of up to 54 wt % using the xanthone derivative α-mangostin (MGS) as a model compound. Evaluation in a tumor-bearing mouse model indicated that a single intravenous administration via the tail vein induced a significantly greater antitumor effect compared with free MGS. These results demonstrate the potential of CDNP_PEGs as promising high-capacity carriers for the delivery of anticancer drugs.</p>","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"6 2","pages":"168-177"},"PeriodicalIF":4.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13087803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147723764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CryoEM Structures of Native Quinol-Dependent Nitric Oxide Reductase in Resting and Quinol-Bound States.","authors":"Faisal T Khaja, Allegra Mboukou, Louie P Aspinall, Charlotte E Hawksworth, Robert R Eady, Svetlana V Antonyuk, Stephen P Muench, S Samar Hasnain","doi":"10.1021/acsbiomedchemau.5c00245","DOIUrl":"10.1021/acsbiomedchemau.5c00245","url":null,"abstract":"<p><p>The membrane-bound quinol-dependent nitric oxide reductases (qNORs), which are members of the respiratory heme-copper oxidase superfamily, are of major importance to food production, environment, and human health. They are unique to bacteria and catalyze N-N bond formation, converting nitric oxide (NO) to generate the enzymatic product, nitrous oxide (N₂O), in agricultural and pathogenic conditions. High-resolution qNOR structures have been reported from two bacterial species, in which the molecular size of the protein was increased by the insertion of apocytochrome b₅₆₂ (BRIL) at the C-terminus to facilitate cryoEM structure determination. However, it remains uncertain how BRIL fusion alters the native structure of these metalloenzymes. Here, we present the first high-resolution structure of <i>Achromobacter xylosoxidans</i> qNOR (<i>Ax</i>qNOR) determined without a fusion tag at two different pH values, revealing structural differences near the catalytic core as well as overall conformational changes between the native and fusion-tagged structures. The native enzyme shows a bell-shaped pH dependence of enzymatic activity, like nitrite reductase, the preceding enzyme in the denitrification pathway, which generates the substrate NO. In addition, we report structures of <i>Ax</i>qNOR bound to quinol and hydroxyquinol that provide valuable insight into the potential electron transfer pathway originating from Trp718 to the redox centers.</p>","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"6 2","pages":"145-159"},"PeriodicalIF":4.3,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13087809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147723758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ligand-Induced Opening of a Cryptic Pocket in METTL14.","authors":"Ivan Corbeski, Rajiv Kumar Bedi, Christian M Matter, Fiona Stamm, Elena Bochenkova, Marcin Herok, Michael J Hartshorn, Amedeo Caflisch","doi":"10.1021/acsbiomedchemau.5c00184","DOIUrl":"https://doi.org/10.1021/acsbiomedchemau.5c00184","url":null,"abstract":"<p><p>The complex of methyltransferase-like proteins 3 and 14 (METTL3-14) is the main human enzyme that deposits the most abundant internal mRNA modification, N⁶-methyladenosine (m⁶A). In the heterodimeric complex, METTL3 acts as a catalytic subunit while METTL14 is involved in mRNA binding and complex stabilization. Here, we present the discovery of small-molecule ligands that bind to a cryptic pocket in METTL14 by protein crystallography. A comparative analysis of crystal structures revealed that the METTL14 cryptic pocket is closed in the apo structure of METTL3-14, and in the structures of METTL3-14 in the complex with the cosubstrate <i>S</i>-adenosyl-methionine (SAM) and a large number of SAM-competitive inhibitors. We first discovered compounds <b>1</b> and <b>2</b> that bind to both the SAM pocket in METTL3 and the cryptic pocket in METTL14. With this structural information, we designed compound <b>3</b> that binds only to the METTL14 cryptic pocket. Compound <b>3</b> does not inhibit the catalytic activity of METTL3-14 but can be used as an anchor for heterobifunctional molecules. We propose a route for its further development into heterobifunctional ligands, e.g., proteolysis targeting chimeras (PROTACs).</p>","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"6 2","pages":"130-144"},"PeriodicalIF":4.3,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13087807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147723842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of Small-Molecule Antagonists of PHF1 and 19 Demonstrates the Ligandability of PRC2 Accessory Proteins.","authors":"Isabelle E Amick, Rebecca L Johnson, Jiuyang Liu, Cameron R Bussey-Sutton, Ikeer Y Mancera-Ortiz, Jacqueline L Norris-Drouin, Shelton R Boyd, Stephanie H Cholensky, Cathy J Spangler, Robert K McGinty, Brian D Strahl, Tatiana G Kutateladze, Stephen V Frye, Lindsey I James","doi":"10.1021/acsbiomedchemau.5c00150","DOIUrl":"10.1021/acsbiomedchemau.5c00150","url":null,"abstract":"<p><p>PHF1 and PHF19 are key accessory components of polycomb repressive complex 2 (PRC2) which is responsible for trimethylation at histone H3 lysine 27, ultimately leading to gene repression. PHF1 and 19 are known for their methyl-lysine reader Tudor domains that recognize methylated lysine 36 on H3, and they have also been implicated as drivers of a range of cancers, including multiple myeloma. Here, we describe the first small-molecule antagonist of the Tudor domains of PHF1 and 19. We screened an internal library of ∼ 1 K compounds against the Tudor domains using a TR-FRET assay. Upon validation of a hit compound, we performed structure-activity relationship (SAR) studies to better understand the binding mode and improve the affinity of the compound for the PHF1 and 19 Tudor domains. One such compound, UNC7242, which binds PHF1 with a <i>K</i> _d of 1.13 ± 0.04 μM and PHF19 with a <i>K</i> _d of 0.64 ± 0.14 μM, emerged as a lead compound. UNC7242 clearly demonstrates the ligandability of these disease-relevant proteins and serves as a starting point for the future development of potent and selective PHF1 and 19 chemical probes.</p>","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"6 2","pages":"101-117"},"PeriodicalIF":4.3,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13087805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147723815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pyrazolylpyrimidinamines Decorated via Petasis Reaction as Small-Molecule Activators of the RNA-Degrading Ribonuclease IRE1α.","authors":"Amrutha K Avathan Veettil, Yang Liu, Leon Wagner, Oguz Hastürk, Nguyen Song Thu Huynh, Giorgia Mancino, Maria Beerbaum, Peng Wu","doi":"10.1021/acsbiomedchemau.5c00161","DOIUrl":"10.1021/acsbiomedchemau.5c00161","url":null,"abstract":"<p><p>The multicomponent Petasis boron-Mannich reaction (PR) enables the generation of functionalized amines that are of biological interest. Here, we demonstrated that a series of pyrazolylpyrimidinamines decorated via PR are new small-molecule activators of the dual kinase and ribonuclease RNA-degrading protein inositol-requiring enzyme 1α (IRE1α), which is an essential effector in the unfolded protein response associated with many human diseases. Compound SH4 was identified via a FRET assay and showed potent activity in activating the IRE1α ribonuclease (RNase) activity, inducing increased <i>XBP1</i> mRNA splicing, and inducing <i>Bloc1s1</i> mRNA degradation. Based on a binding mode analysis, the following series of PR-decorated functionalized amines was further probed as IRE1α RNase activators. One PR-derived compound, AK177, showed nanomolar activating potency in biochemical assays but minimal activities in cellular evaluations. Overall, we present here a series of pyrazolylpyrimidinamines as new small-molecule activators of the IRE1α RNase activity, which served as the first examples of applying PR in accessing bioactive compounds targeting the kinase domain of a ribonuclease involved in mRNA cleavage and splicing.</p>","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"6 2","pages":"118-129"},"PeriodicalIF":4.3,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13087800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147723810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Photoinduced Electron Transfer Informs on Pathway Coupling in Flavin-Based Electron Bifurcation.","authors":"Seth A Wiley, Carolyn E Lubner","doi":"10.1021/acsbiomedchemau.5c00232","DOIUrl":"https://doi.org/10.1021/acsbiomedchemau.5c00232","url":null,"abstract":"<p><p>Flavin-based electron bifurcation (FBEB) is an enzymatic mechanism that generates extremely high-energy electrons to drive unfavorable chemical reactions. It is utilized by the NADH-dependent ferredoxin:NADP⁺-oxidoreductase (Nfn) enzyme in hyperthermophile <i>Pyrococcus furiosus</i> to bifurcate electrons from NADPH into the coupled low-potential (endergonic) and high-potential (exergonic) pathways. This process enables <i>P. furiosus</i> to live in harsh and uninviting environments. Despite its biological importance, the mechanisms used by Nfn to facilitate exceptional directional control over short-lived, high-energy electrons and to prevent undesired transfer, particularly along the low-potential pathway, are still not well understood. To elucidate how the protein environment contributes to electronic control in the low-potential pathway, new techniques must be utilized to probe these unstable intermediates. In this study, we have adapted low-temperature photoexcitation combined with electron paramagnetic resonance (EPR) to accumulate the short-lived intermediate and place it in the context of the other cofactors involved in the low-potential pathway of Nfn. We observed coincident growth of both the radical intermediate and its nearby [4Fe-4S] cluster over 4.5 h of illumination with NADPH at cryogenic temperatures. The photogenerated paramagnetic species were stable in LN₂ storage indefinitely and recombined when warmed to higher temperatures. The results provide insights into the electron transfer steps and cofactor interactions along the low potential pathway, facilitating a more robust mechanistic understanding of the high-energy events of electron bifurcation. Furthermore, through comparison of cryogenic and room temperature experiments, a potential gating step involving the movement of key residues important for the reversibility of electron flow along this pathway is suggested.</p>","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"6 1","pages":"78-89"},"PeriodicalIF":4.3,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12921514/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147272114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of <i>N</i>‑Acylhydrazone Derivatives as ROCK Inhibitors: A Journey from Virtual Screening and Structure-Based De Novo Design to the Identification of ROCK2 Selective Inhibitors and Beyond.","authors":"Pedro de Sena Murteira Pinheiro, Lucas Silva Franco, Raysa Magali Pillpe-Meza, Bárbara da Silva Mascarenhas de Jesus, Gabrielli Ayumi Ito Martins, Wesley Leandro Gouveia, Daniel Alencar Rodrigues, Marina Amaral Alves, Lídia Moreira Lima","doi":"10.1021/acsbiomedchemau.5c00246","DOIUrl":"10.1021/acsbiomedchemau.5c00246","url":null,"abstract":"<p><p>Rho-associated coiled-coil containing kinases (ROCK1 and ROCK2) are central regulators of actin cytoskeleton organization and cell contractility under physiological conditions. Dysregulation of ROCK signaling contributes to aberrant cell migration, invasion, and tissue remodeling, positioning these kinases as attractive therapeutic targets in cancer and fibrotic diseases. In this work, we report the discovery of <i>N</i>-acylhydrazone (NAH) derivatives as potent and selective ROCK inhibitors, integrating structure-based virtual screening (SBVS), de novo design, and biological evaluation. Initial hit identification from the LASSBio Chemical Library revealed three inhibitors (LASSBio-1828 (<b>1</b>), LASSBio-1829 (<b>2</b>), and LASSBio-1919 (<b>3</b>)), which guided the rational design of a virtual library of 321 NAH analogues. Docking-based prioritization, synthesis, and SAR exploration yielded compounds with low nanomolar potency, among which LASSBio-2360 (<b>12</b>), LASSBio-2380 (<b>17</b>), and LASSBio-2382 (<b>18</b>) exhibited dual ROCK1/2 inhibition (IC₅₀ values in the 1-15 nM range), while LASSBio-2389 (<b>21</b>) showed remarkable ROCK2 selectivity (IC₅₀ = 0.051 μM; 21-fold vs ROCK1 - IC₅₀ = 1.143 μM) and minimal inhibition of other related kinases at 500 nM. Molecular dynamics simulations demonstrated that <b>21</b> stabilizes the DFG-out conformation of ROCK2, providing a structural rationale for isoform selectivity. In vitro studies using MDA-MB-231 triple-negative breast cancer cells confirmed that compounds <b>12</b>, <b>17</b>, <b>18</b>, and <b>21</b> inhibit migration more effectively than fasudil and comparably to belumosudil. Altogether, this work identifies NAH as a privileged scaffold for ROCK inhibition, delineates the molecular determinants of ROCK2 selectivity, and highlights new chemical leads for the development of antimetastatic and antifibrotic agents targeting the Rho/ROCK pathway.</p>","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"6 2","pages":"192-209"},"PeriodicalIF":4.3,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13087806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147723846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MAPK Pathway Inhibition Reshapes Kinase Chemical Probe Reactivity Reflecting Cellular Activation States.","authors":"Andrew F Jarvis, Mohd Younis Bhat, Timothé Maujean, Ahlenne L Abreu, Kaitlyn Toy, George M Burslem, Donita C Brady","doi":"10.1021/acsbiomedchemau.5c00231","DOIUrl":"10.1021/acsbiomedchemau.5c00231","url":null,"abstract":"<p><p>Despite the pivotal role of oncogenic kinases in cancer initiation, progression, and therapeutic resistance, functionally profiling their activity and conformational dynamics in live cells remains challenging. Existing methods often fail to capture inhibitor-bound structural states of kinases, particularly in clinically relevant contexts, such as treatment response and acquired resistance, where genomic data alone are insufficient. Here, we use activity-based protein profiling (ABPP) to monitor composite amino acid reactivity changes, across cysteine, lysine, and carboxylic acid residues, as a hypothesis-generating readout of kinase state in live cells. Using electrophilic probes, we show that treatment of BRAFV600E mutant melanoma cells with vemurafenib or trametinib decreases overall cysteine and lysine reactivity in BRAFV600E and MEK1/2, likely reflecting composite changes in amino acid accessibility across multiple reactive residues associated with inhibitor binding. Changing the order of probe addition and inhibitor treatment altered the labeling outcomes, consistent with competitive engagement and structural stabilization. Comparative analysis of ATP-competitive BRAFV600E inhibitors vemurafenib and dabrafenib indicated differences in aspartate and glutamate labeling patterns, consistent with the possibility that ABPP may detect inhibitor-associated variations in residue accessibility, which could reflect differences in inhibitor-bound conformations. In inhibitor-resistant melanoma models, ABPP detected differences in residue reactivity relative to parental cells, which aligned with known resistance-associated features, such as BRAF overexpression and the MEK2 Q60P activation mutation. Moreover, global proteome analyses of cysteine and lysine reactivity upon BRAFV600E inhibition revealed probe-accessible cysteine labeling changes on KSR2, suggesting a potential MAPK pathway remodeling. Together, these findings highlight ABPP as a valuable chemical biology approach for investigating inhibitor-dependent changes in kinase residue reactivity, offering a framework to investigate how kinase conformational dynamics and signaling pathway adaptation influence the therapeutic response and resistance in cancer.</p>","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"6 2","pages":"178-191"},"PeriodicalIF":4.3,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13087801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147723824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fine-Tuning a Transformer Model for METTL3 Lead Optimization.","authors":"Christian M Matter, Amedeo Caflisch","doi":"10.1021/acsbiomedchemau.5c00198","DOIUrl":"10.1021/acsbiomedchemau.5c00198","url":null,"abstract":"<p><p>Transformers are machine learning models originally developed to translate between natural languages. Recently, a transformer model was trained on knowledge of medicinal chemistry, i.e., matched molecular pairs of nearly a million bioactive compounds from the ChEMBL database. Here, we customize (i.e., fine-tune) the pretrained model to enhance the affinity and/or metabolic stability of a series of inhibitors of methyltransferase-like protein 3 (METTL3). We first fine-tune the transformer model using a data set of about 500 METTL3 inhibitors with known binding affinities and validate it by retrospective analysis. Then, we fine-tune the original transformer model to simultaneously optimize binding affinity and metabolic stability in a prospective application. Two of the five METTL3 inhibitors predicted by the multiobjective optimized model show low-nanomolar potency and higher stability than the lead compound of the chemical series used for fine-tuning.</p>","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"6 2","pages":"160-167"},"PeriodicalIF":4.3,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13087808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147723818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"OBIMAP (One-Bead Interchain Multipeptide Assembly Platform).","authors":"Othman Al Musaimi, Daryl R Williams","doi":"10.1021/acsbiomedchemau.5c00237","DOIUrl":"https://doi.org/10.1021/acsbiomedchemau.5c00237","url":null,"abstract":"<p><p>A significant advancement in Merrifield's classic solid-phase peptide synthesis (SPPS) that greatly expands the scope of accessible peptide structures is reported here. Building upon the one-bead, one-compound (OBOC) concept, this approach enables the simultaneous synthesis of multiple peptides on a single bead, followed by a novel solid-phase interchain assembly reaction to produce the final peptide product. This method, the one-bead interchain multipeptide assembly platform (OBIMAP), successfully generates diverse peptide architectures, including linear, cyclic, and bicyclic structuresranging from minimal cyclic dipeptides to small proteinsmany of which are inaccessible through conventional SPPS. OBIMAP demonstrates superior efficiency in both time and product purity compared to traditional methods. Crucially, it eliminates the need for solution-phase fragment condensation, a common but cumbersome step commonly used in synthesizing therapeutic peptides (30-60 amino acids). In addition to enhancing conventional SPPS methodologies, the OBIMAP enables access to novel classes of peptide architectures, including highly constrained peptides that were previously considered synthetically inaccessible.</p>","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"6 1","pages":"90-100"},"PeriodicalIF":4.3,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12921515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147272084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}