Bioorganic Chemistry最新文献

{"title":"Enhancing rhamnolipid production via immobilized Pseudomonas stutzeri lipase: A comparative study","authors":"Guillermo Cruz,&nbsp;Cecilia García-Oliva,&nbsp;Almudena Perona,&nbsp;Pilar Hoyos,&nbsp;María J. Hernáiz","doi":"10.1016/j.bioorg.2024.107855","DOIUrl":"10.1016/j.bioorg.2024.107855","url":null,"abstract":"<div><div>Rhamnolipids (RLs) are widely studied biosurfactants with significant industrial potential in cosmetics, pharmaceuticals, and bioremediation due to their excellent surface activity, emulsifying properties and bioactive characteristics. However, high production costs impede their mass production. This study investigates the immobilization of <em>Pseudomonas stutzeri lipase</em> (PSL) on various supports to enhance RL synthesis efficiency, focusing on yield and regioselectivity in the enzymatic synthesis of 4-O-lauroylrhamnose by the transesterification of rhamnose with vinyl laurate. Three immobilization methods were compared: covalent binding, adsorption on Celite, and adsorption on hydrophobic supports. The immobilization efficiency varied depending on the method used, with the lowest observed for adsorption on Celite (56 %), followed by covalent immobilization on Sepabeads (EC-EP/S 78 % and EC-EP/L 70 %), and the highest for adsorption on hydrophobic supports (83–97 %, with EC-OD being the best at 97 %). For the enzymatic synthesis of 4-O-lauroylrhamnose, covalent immobilization on Sepabeads™ EC-EP yielded low conversions due to restricted conformational freedom of the enzyme. Celite® 545 adsorption resulted in moderate conversion rates, limited by the electrostatic interactions restricting enzyme activity. The most promising results were obtained with hydrophobic supports, particularly Purolite® ECR8806F, achieving nearly complete conversion and maintaining high regioselectivity at the 4-position of rhamnose in both THF and the green solvent 2-methyltetrahydrofuran (2-MeTHF). The study highlights the critical role of support hydrophobicity and active surface area in the immobilized enzyme performance. PSL immobilized on Purolite® ECR8806F demonstrated significant potential for sustainable RLs production, showing excellent reusability, stability and productivity across multiple reaction cycles. This study presents a significant advancement in RLs production by optimizing PSL immobilization and reaction conditions, facilitating the way for more cost-effective and sustainable industrial applications.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"153 ","pages":"Article 107855"},"PeriodicalIF":4.5,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of a Potent, selective and orally bioavailable CDK9 degrader for targeting transcription regulation in Triple-Negative breast cancer","authors":"Hui-Jun Nie ,&nbsp;Ben-Fu Li ,&nbsp;Jingya Sun ,&nbsp;Yali Yuan ,&nbsp;Zhi-Gao Zhang ,&nbsp;Hao Hu ,&nbsp;Wen-Jing Wang ,&nbsp;Ziqiang Chen ,&nbsp;Simei Wang ,&nbsp;Wensi Huang ,&nbsp;Xingxing Diao ,&nbsp;Jinghua Yu ,&nbsp;Ruimin Huang ,&nbsp;Xiao-Hua Chen","doi":"10.1016/j.bioorg.2024.107876","DOIUrl":"10.1016/j.bioorg.2024.107876","url":null,"abstract":"<div><div>Triple-negative breast cancer (TNBC) is a highly aggressive, heterogeneous and invasive subtype of breast cancer with very limited effective modalities of treatment. Degrading the critical transcription regulator cyclin-dependent kinase 9 (CDK9) by proteolysis targeting chimeras (PROTACs) has shown promising potential for treating TNBC. However, to date, CDK9-targeting PROTACs for oral administration in treatment of cancers have not been reported. We herein present the design, synthesis, and extensive biological evaluation of a series of novel PROTACs as orally bioavailable, potent and selective degraders of CDK9 for targeting transcription regulation in triple-negative breast cancer. The developed compound <strong>29</strong> exhibited a desired potency (DC₅₀ = 3.94 nM) with high efficacy (D_max = 96 %) on CDK9 degradation, and effectively inhibited the proliferation of TNBC MDA-MB-231 cells. Mechanistic investigations revealed that compound <strong>29</strong> is a <em>bona fide</em> CDK9 degrader and can substantially downregulate the downstream targets c-Myc and MCL-1. Furthermore, compound <strong>29</strong> displayed favorable oral bioavailability in mice, and oral administration of degrader <strong>29</strong> significantly depleted CDK9 protein in TNBC tumor tissues and exhibited tumor growth inhibition in TNBC xenograft mice models. Collectively, our work established that degrader <strong>29</strong> is a highly potent and selective degraders of CDK9 with satisfactory oral bioavailability, which holds promising potential for the treatment of TNBC.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"153 ","pages":"Article 107876"},"PeriodicalIF":4.5,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142433960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chromene-based compounds as drug candidates for renal and bladder cancer therapy – A systematic review","authors":"Mónica Costa Cerqueira ,&nbsp;Ana Silva ,&nbsp;Sofia Martins Sousa ,&nbsp;Filipa Pinto-Ribeiro ,&nbsp;Fátima Baltazar ,&nbsp;Julieta Afonso ,&nbsp;Marta Freitas Costa","doi":"10.1016/j.bioorg.2024.107865","DOIUrl":"10.1016/j.bioorg.2024.107865","url":null,"abstract":"<div><div>Renal (RC) and bladder cancers (BC) are common urological malignancies prevalent in the male population. Incidence and mortality rates are expected to increase in the near future. Drug toxicity and development of drug resistance in both diseases are major obstacles to achieve successful treatments. Chromenes are heterocyclic compounds constituted by a benzene ring fused to a pyran nucleus. Natural and synthetic chromene-based compounds have proven to be promising anticancer agents. Additionally, re-sensitization of cancer cells to classical treatments has also been demonstrated. Thus, the aim of this systematic review is to assess the potential of chromene-based compounds in the treatment of RC and BC. Study collection was performed in six different databases, to compile existing information on preclinical (<em>in vitro</em> and <em>in vivo</em>) and clinical studies developed to date. Overall, multiple chromene-based compounds showed potent anticancer effects, affecting several biological features such as reduction in cell viability, proliferation, migration and invasion <em>in vitro</em>, and induction of cell cycle arrest and cell death. Tumor volume and weight were generally decreased <em>in vivo</em> upon chromene-based treatment. Modest results have been obtained in two clinical trials, with reports of a partial response and two objective responses in RC patients. Thus, the chromene family can be considered an attractive chemical scaffold, harboring promising drug candidates for RC and BC therapeutics.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"153 ","pages":"Article 107865"},"PeriodicalIF":4.5,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142405775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Facile constructed meroterpenoids with novel hexadecahydroacephenanthrylene carbon skeleton using the biotransformation and chemical synthesis method.","authors":"Die Yan, Binglin Chang, Qingcui Li, Yuqian Tang, Jingxin He, Yena Liu, Hui Cui","doi":"10.1016/j.bioorg.2024.107871","DOIUrl":"https://doi.org/10.1016/j.bioorg.2024.107871","url":null,"abstract":"<p><p>Bioaspermeroterpenoid A (1), the first meroterpenoid with an unprecedented hexadecahydroacephenanthrylene carbon skeleton, together with two analogues bioaspermeroterpenoids B and C (2 and 3) were co-isolated from the biotransformation extract of aspermeroterpene C by the fungus Penicillium herquei GZU-31-6. On the other hand, bioaspermeroterpenoid Aa (1a) featuring the same hexadecahydroacephenanthrylene carbon skeleton was synthesized from the precursor aspermeroterpene C by the nucleophilic addition reaction in the presence of CH₃ONa. Furthermore, bioaspermeroterpenoids A and C showed good inhibitory activities against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 cells with IC₅₀ values of 26.08 and 7.50 µM, respectively, compared to the positive control (Indomethacin, IC₅₀ 24.1 µM). Especially, bioaspermeroterpenoids A and C also significantly suppressed the protein expression of iNOS and COX-2 at the concentration of 12.5 μM.</p>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"153 ","pages":"107871"},"PeriodicalIF":4.5,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 biological evaluation of novel 5,7,4′-trimethoxyflavone sulfonamide-based derivatives as highly potent inhibitors of LRPPRC/STAT3/CDK1","authors":"Rui Wu ,&nbsp;Pan Li ,&nbsp;Bingbing Hao ,&nbsp;Mangaladoss Fredimoses ,&nbsp;Yunxiao Ge ,&nbsp;Yubing Zhou ,&nbsp;Lin Tang ,&nbsp;Yuanying Li ,&nbsp;Hangrui Liu ,&nbsp;Victor Janson ,&nbsp;Yamei Hu ,&nbsp;Hui Liu","doi":"10.1016/j.bioorg.2024.107878","DOIUrl":"10.1016/j.bioorg.2024.107878","url":null,"abstract":"<div><div>Leucine-rich pentatricopeptide repeat-containing protein (LRPPRC), signal transducer and activator of transcription 3 (STAT3), and cyclin-dependent kinase 1 (CDK1) are promising therapeutic targets for cancer treatment. However, there is a lack of effective inhibitors of LRPPRC, STAT3, and CDK1 in clinic. Our previous study has proved that 5,7,4′-Trimethoxyflavone (TMF) is a novel inhibitor of LRPPRC/STAT3/CDK1. However, the extraction rate of TMF from Tangerine Peel is quite low, and the doses of TMF in cells and mice are rather high. Herein, structural modifications of TMF have led to two series of TMF derivatives including sulfonamide substituted at 3′-position (<strong>7a</strong>–<strong>m</strong>) and 3′,8-position (<strong>11a</strong>–<strong>m</strong>). Among all compounds, <strong>7e</strong>, <strong>7k</strong>, <strong>11e</strong>, and <strong>11g</strong> exhibited as effective, broad-spectrum, and potent anticancer agents <em>in vitro</em>. Moreover, <strong>7e</strong>, <strong>7k</strong>, <strong>11e</strong>, and <strong>11g</strong> showed better antitumor effects than TMF and clinical used chemotherapy drug capecitabine <em>in vivo</em> with no obvious toxicity. Mechanism studies showed that <strong>11g</strong> could bind to LRPPRC, STAT3, and CDK1 to disassociate the LRPPRC-JAK2-STAT3 and JAK2-STAT3-CDK1 complexes, resulting in suppression of JAK2/STAT3 signaling pathway. These findings suggest that <strong>11g</strong> may serve as a leading compound for cancer therapy as a triple-target (LRPPRC, STAT3, and CDK1) inhibitor.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"153 ","pages":"Article 107878"},"PeriodicalIF":4.5,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142417666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of novel and potent sulfonamide derivatives as orally available drug for psoriasis","authors":"Liang Qi,&nbsp;Yi-Nuo Ping,&nbsp;Shang-Shang Sun,&nbsp;Ran Xu,&nbsp;Xin-Ru Zhou","doi":"10.1016/j.bioorg.2024.107853","DOIUrl":"10.1016/j.bioorg.2024.107853","url":null,"abstract":"<div><div>The retinoid-related orphan receptor gamma-t (RORγt), a member of the nuclear receptor superfamily, functions as a ligand-dependent transcription factor. As a pivotal modulator in the development and functionality of <em>T</em>-helper 17 (Th17) cells, RORγt plays a crucial role in immune response regulation. Inverse agonists targeting RORγt demonstrate significant potential in modulating Th17 cell activity, offering a promising avenue for the development of therapeutics aimed at treating autoimmune diseases associated with Th17 dysregulation. GSK2981278 is a potent RORγt inverse agonist, but a drawback of GSK2981278 is its low pharmacokinetic profile, leading to a clinical failure. We have explored detailed structure–activity relationship of GSK2981278 trying to improve metabolic stability while maintaining RORγt activity. As a result, a novel series of sulfonamide derivatives was discovered as potent RORγt inverse agonists with improved drug-like properties. <strong>b14</strong> had greatly improved In Vitro metabolic stability (T_1/2 = 36.2 min) compared to GSK2981278 (T_1/2 = 0.8 min). Oral dosing of compound <strong>b14</strong> resulted in a dose-dependent suppression of IL-17A cytokine levels within a murine model of imiquimod-induced skin inflammation, underscoring its potential as a therapeutic intervention.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"153 ","pages":"Article 107853"},"PeriodicalIF":4.5,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142417836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial metabolomics to discover hypertrophic scar relevant metabolic alterations and potential therapeutic strategies: A preliminary study","authors":"Jingyun Li ,&nbsp;Siqi Zeng ,&nbsp;Enyuan Zhang ,&nbsp;Ling Chen ,&nbsp;Jingbin Jiang ,&nbsp;Jun Li","doi":"10.1016/j.bioorg.2024.107873","DOIUrl":"10.1016/j.bioorg.2024.107873","url":null,"abstract":"<div><div>Spatially mapping the metabolic remodeling of hypertrophic scar and surrounding normal skin tissues has the potential to enhance our comprehension of scar formation and aid in the advancement of therapeutic interventions. In this study, we employed matrix-assisted laser desorption/ionization (MALDI), a mass spectrometry imaging technique, to visualize the hierarchical distribution of metabolites within sections of hypertrophic scar and surrounding normal skin tissues. A comprehensive analysis identified a total of 1631 metabolites in these tissues. The top four classes that were identified included benzene and substituted derivatives, heterocyclic compounds, amino acids and its metabolites, and glycerophospholipids. In hypertrophic scar tissues, 22 metabolites were upregulated and 66 metabolites were downregulated. MetaboAnalyst pathway analysis indicated that glycerophospholipid metabolism was primarily associated with these altered 88 metabolites. Subsequently, six metabolites were selected, their spatial characteristics were analyzed, and they were individually added to the cell culture medium of primary hypertrophic scar fibroblasts. The preliminary findings of this study demonstrate that specific concentrations of 1-pyrrolidinecarboxamide, 2-benzylideneheptanal, glycerol trioleate, Lyso-PAF C-16, and moxonidine effectively inhibited the expressions of COL1A1, COL1A2, COL3A1, and ACTA2. These bioactive metabolites exhibit mild and non-toxic properties, along with favorable pharmacokinetics and pharmacodynamics, making them promising candidates for drug development. Consequently, this research offers novel therapeutic insights for hypertrophic scar treatment.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"153 ","pages":"Article 107873"},"PeriodicalIF":4.5,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in designing ternary complexes: Integrating in-silico and biochemical methods for PROTAC optimisation in target protein degradation","authors":"Shareef Shaik ,&nbsp;Prasanna Kumar Reddy Gayam ,&nbsp;Manish Chaudhary ,&nbsp;Gurvinder Singh ,&nbsp;Aravinda Pai","doi":"10.1016/j.bioorg.2024.107868","DOIUrl":"10.1016/j.bioorg.2024.107868","url":null,"abstract":"<div><div>Target protein degradation (TPD) is an emerging approach to mitigate disease-causing proteins. TPD contains several strategies, and one of the strategies that gained immersive importance in recent times is Proteolysis Targeting Chimeras (PROTACs); the PROTACs recruit small molecules to induce the poly-ubiquitination of disease-causing protein by hijacking the ubiquitin–proteasome system (UPS) by bringing the E3 ligase and protein of interest (POI) into appropriate proximity. The steps involved in designing and evaluating the PROTACs remain critical in optimising the PROTACs to degrade the POI. It is observed that using in-silico and biochemical methods to study the ternary complexes (TCs) of the POI-PROTAC-E3 ligase is essential to understanding the structural activity, cooperativity, and stability of formed TCs. A better understanding of the above-mentioned leads to an appropriate rationale for designing the PROTACs targeting the disease-causing proteins. In this review, we tried to summarise the approaches used to design the ternary complexes, i.e., <em>in-silico</em> and <em>in-vitro</em> methods, to understand the behaviour of the PROTAC-induced ternary complexes.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"153 ","pages":"Article 107868"},"PeriodicalIF":4.5,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pyrrolo[2,3-d]pyrimidines as potential kinase inhibitors in cancer drug discovery: A critical review","authors":"Malyala Sai Madhurya ,&nbsp;Vanashree Thakur ,&nbsp;Sowmya Dastari,&nbsp;Nagula Shankaraiah","doi":"10.1016/j.bioorg.2024.107867","DOIUrl":"10.1016/j.bioorg.2024.107867","url":null,"abstract":"<div><div>Pyrrolo[2,3-<em>d</em>]pyrimidine-based kinase inhibitors have emerged as an important class of targeted therapeutics to combat various types of cancer. The distinctive structural feature of pyrrolopyrimidine ring system offers an adaptable platform for designing potent inhibitors of various kinases, crucial in regulating cellular processes. The deazapurine framework inherent to pyrrolopyrimidines bears a conspicuous resemblance to adenine, the natural ligand ATP. The structural mimicry enhances their appeal as potent inhibitors of key kinases. This review reconnoitres the intricate process of designing and developing pyrrolopyrimidine based derivatives, accentuating their structural diversity and the strategic modifications employed to enhance selectivity, potency, and pharmacokinetic properties. The discussion delves into medicinal chemistry strategies, highlighting successful examples that have been progressed to clinical evaluation. Furthermore, the review highlights the promise of pyrrolopyrimidine scaffolds in revolutionizing targeted cancer therapy and provides a pioneering perspective on future directions.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"153 ","pages":"Article 107867"},"PeriodicalIF":4.5,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142398893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Opportunities and challenges for targeting HPK1 in cancer immunotherapy","authors":"Jiamei Xu ,&nbsp;Yingzhou Li ,&nbsp;Xinyi Chen ,&nbsp;Junyi Yang ,&nbsp;Heye Xia ,&nbsp;Wenhai Huang ,&nbsp;Shenxin Zeng","doi":"10.1016/j.bioorg.2024.107866","DOIUrl":"10.1016/j.bioorg.2024.107866","url":null,"abstract":"<div><div>Hematopoietic Progenitor Kinase 1 (HPK1, also known as MAP4K1) is a hematopoiesis-specific serine/threonine kinase that belongs to the MAP4K family of Ste20-related protein kinases. HPK1 has been identified as a negative regulator of <em>T</em>-cell receptor signaling. Recent studies have indicated that the inhibition or knockout of HPK1 kinase function can effectively alleviate T cell exhaustion, enhance T cell functionality, and improve the therapeutic efficacy of tumor immunotherapy. In recent years, small molecule chemical drugs targeting HPK1 have made significant progress and have become a hot topic in the research and development of tumor immunotherapy drugs. However, the advancement of small molecule drugs that target HPK1 is hindered by various challenges, including the limited selectivity, insufficient immune stimulation, and the ambiguity surrounding role of non-kinase scaffold functions of HPK1 in tumor immune responses. This review briefly describes the biological structure of HPK1 and its related signaling pathways in tumor immunity, systematically discusses the latest research progress in small molecule chemical drugs targeting HPK1. Finally, we summarize and prospect the opportunities and challenges in the drug development of small molecule chemical drugs targeting HPK1 in tumor immunity.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"153 ","pages":"Article 107866"},"PeriodicalIF":4.5,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}