We are analyzing https://link.springer.com/article/10.1007/s11030-025-11166-x.

Title:
Design, synthesis, and biological evaluation of RIPK1-targeting PROTACs | Molecular Diversity
Description:
Cancer cells can hijack receptor-interacting protein kinase 1 (RIPK1) and exploit its scaffolding function to orchestrate pro-survival signaling and fuel immunosuppressive program. Accordingly, targeting RIPK1 for elimination has emerged as a promising anti-cancer strategy. Based on the RIPK1 inhibitor 4 previously reported by our group, we employed proteolysis targeting chimera (PROTAC) technology and designed a series of RIPK1 degraders. Structure–activity relationship (SAR) study revealed three types of ligands for E3 ligase — cereblon (CRBN), von Hippel-Lindau (VHL) and inhibitor of apoptosis protein (IAP) — demonstrated varied efficacy in RIPK1 degradation of human and mouse cells. The VHL-based compound 18 exhibited potent RIPK1 degradation activity in both human and mouse cellular scenarios. Further biological evaluation confirmed that compound 18 potently induced RIPK1 degradation of I2.1 cells with a DC50 value of 274.4 nM and maintained long-term and dramatic RIPK1 degradation within 72 h. This study provided important insights into future development of RIPK1-PORTACs, and compound 18 was a promising RIPK1 degrader candidate.
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28 years and 1 months (reg. 1997-05-29).

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Keywords {🔍}

article, pubmed, google, scholar, cas, ripk, zhang, cell, central, investigation, data, protein, drug, duan, death, mol, chem, wang, kinase, degradation, research, lan, peng, jing, wenhu, cancer, targeting, protac, access, nat, rev, discovery, shanghai, china, privacy, cookies, content, information, molecular, shuonan, inhibitors, target, yuan, med, nature, curation, methodology, springer, publish, search,

Topics {✒️}

month download article/chapter structure–activity relationship tanshinone iia-mediated modulation tnf-induced cell death snipers-hijacking iap activity promising anti-cancer strategy orchestrate pro-survival signaling ripk1-fadd-caspase 8 complex cancer immunotherapy target proteolysis targeting chimeras full article pdf potent necroptosis inhibitors targeted protein degradation induce protein degradation dramatic ripk1 degradation privacy choices/manage cookies immunogenic cell death shandong laboratory program cell death pathways cell death signaling nonapoptotic cell death selective receptor flexibility kinase-ligand interactions writing-original draft accepted manuscript version writing-review & editing writing–review & editing ripk1-targeting protacs hdacs dual inhibitors holds exclusive rights european economic area von hippel-lindau maintained long-term related subjects sequential signaling complexes ischemic brain injury pyridin-2-amine derivatives technological innovation cooperation 19a yuquan road china pharmaceutical university wenhu duan ethics declarations conflict ripk1 regulates targeting scaffolding functions bifunctional protac degraders jing ai conditions privacy policy additional information publisher' ripk1 degradation ripk1 degrader

Schema {🗺️}

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            type:Organization
            name:China Pharmaceutical University
            address:
               name:Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, Center for Drug Discovery, China Pharmaceutical University, Nanjing, China
               type:PostalAddress
            type:Organization
      name:Jing Ai
      affiliation:
            name:Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences
            address:
               name:Cancer Research Center, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai, China
               type:PostalAddress
            type:Organization
            name:Bohai Rim Advanced Research Institute for Drug Discovery
            address:
               name:Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai, China
               type:PostalAddress
            type:Organization
            name:University of Chinese Academy of Sciences
            address:
               name:School of Pharmacy, University of Chinese Academy of Sciences, Beijing, China
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Wenhu Duan
      affiliation:
            name:Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences
            address:
               name:Small-Molecule Drug Research Center, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai, China
               type:PostalAddress
            type:Organization
            name:Bohai Rim Advanced Research Institute for Drug Discovery
            address:
               name:Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai, China
               type:PostalAddress
            type:Organization
            name:University of Chinese Academy of Sciences
            address:
               name:School of Pharmacy, University of Chinese Academy of Sciences, Beijing, China
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Small-Molecule Drug Research Center, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai, China
      name:Cancer Research Center, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai, China
      name:School of Pharmacy, University of Chinese Academy of Sciences, Beijing, China
      name:Small-Molecule Drug Research Center, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai, China
      name:School of Pharmacy, University of Chinese Academy of Sciences, Beijing, China
      name:Small-Molecule Drug Research Center, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai, China
      name:School of Pharmacy, University of Chinese Academy of Sciences, Beijing, China
      name:Cancer Research Center, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai, China
      name:Cancer Research Center, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai, China
      name:Small-Molecule Drug Research Center, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai, China
      name:School of Pharmacy, University of Chinese Academy of Sciences, Beijing, China
      name:Small-Molecule Drug Research Center, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai, China
      name:Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, Center for Drug Discovery, China Pharmaceutical University, Nanjing, China
      name:Cancer Research Center, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai, China
      name:Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai, China
      name:School of Pharmacy, University of Chinese Academy of Sciences, Beijing, China
      name:Small-Molecule Drug Research Center, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai, China
      name:Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai, China
      name:School of Pharmacy, University of Chinese Academy of Sciences, Beijing, China
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