Development of decoy oligonucleotide-warheaded chimeric molecules targeting STAT3

Shih, Po-Chang; Naganuma, Miyako; Tsuji, Genichiro; Demizu, Yosuke; Naito, Mikihiko

doi:10.1016/j.bmc.2023.117507

Cited by 4 publications

(5 citation statements)

References 19 publications

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“…D Chemical structures of the antibody-PROTAC conjugate (adapted from [ 125 ]). E Chemical structures of the antibody-PROTAC conjugate (adapted from [ 126 ]) …”

Section: Biomacromolecule-protac Conjugatesmentioning

confidence: 99%

“…Lately, Shih et al . also effectively induced the degradation of STAT3 using a novel aptamer-PROTAC conjugate technology [ 126 ]. Their study demonstrated that the decoy aptamer, which was specifically engineered for STAT3, exhibited a high affinity for binding to the E3 conjugate.…”

Section: Biomacromolecule-protac Conjugatesmentioning

confidence: 99%

“…D Chemical structures of the antibody-PROTAC conjugate (adapted from [125]). E Chemical structures of the antibody-PROTAC conjugate (adapted from [126]) This is achieved through the preferential breaking of the disulfide link by endogenous GSH upon import into tumor cells. In addition to its selectivity, NGP-53 has also demonstrated promising anti-tumor effects without significant adverse effects in preclinical studies using the MCF-7 xenograft model.…”

Section: Aptamer-protac Conjugatesmentioning

confidence: 99%

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New-generation advanced PROTACs as potential therapeutic agents in cancer therapy

Wang,

Zhang,

Chen

et al. 2024

Mol Cancer

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Proteolysis-targeting chimeras (PROTACs) technology has garnered significant attention over the last 10 years, representing a burgeoning therapeutic approach with the potential to address pathogenic proteins that have historically posed challenges for traditional small-molecule inhibitors. PROTACs exploit the endogenous E3 ubiquitin ligases to facilitate degradation of the proteins of interest (POIs) through the ubiquitin–proteasome system (UPS) in a cyclic catalytic manner. Despite recent endeavors to advance the utilization of PROTACs in clinical settings, the majority of PROTACs fail to progress beyond the preclinical phase of drug development. There are multiple factors impeding the market entry of PROTACs, with the insufficiently precise degradation of favorable POIs standing out as one of the most formidable obstacles. Recently, there has been exploration of new-generation advanced PROTACs, including small-molecule PROTAC prodrugs, biomacromolecule-PROTAC conjugates, and nano-PROTACs, to improve the in vivo efficacy of PROTACs. These improved PROTACs possess the capability to mitigate undesirable physicochemical characteristics inherent in traditional PROTACs, thereby enhancing their targetability and reducing off-target side effects. The new-generation of advanced PROTACs will mark a pivotal turning point in the realm of targeted protein degradation. In this comprehensive review, we have meticulously summarized the state-of-the-art advancements achieved by these cutting-edge PROTACs, elucidated their underlying design principles, deliberated upon the prevailing challenges encountered, and provided an insightful outlook on future prospects within this burgeoning field.

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“…D Chemical structures of the antibody-PROTAC conjugate (adapted from [ 125 ]). E Chemical structures of the antibody-PROTAC conjugate (adapted from [ 126 ]) …”

Section: Biomacromolecule-protac Conjugatesmentioning

confidence: 99%

Section: Biomacromolecule-protac Conjugatesmentioning

confidence: 99%

Section: Aptamer-protac Conjugatesmentioning

confidence: 99%

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New-generation advanced PROTACs as potential therapeutic agents in cancer therapy

Wang,

Zhang,

Chen

et al. 2024

Mol Cancer

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“…In addition to selective small molecules used as the STAT3 bait, Shih et al ( 238 ) used a decoy oligonucleotide as the STAT3 bait. The decoy oligonucleotide was the same as that used by Grandis et al in their STAT3 decoy ( 228 , 231 , 232 ).…”

Section: Targeting the Stat3 Pathway In Cancermentioning

confidence: 99%

“…The decoy oligonucleotide was the same as that used by Grandis et al in their STAT3 decoy ( 228 , 231 , 232 ). Shih et al ( 238 ) found that this oligonucleotide-based STAT3 inhibitor reduced STAT3 expression and suppressed cancer cell viability in vitro .…”

Section: Targeting the Stat3 Pathway In Cancermentioning

confidence: 99%

Role of STAT3 in cancer cell epithelial‑mesenchymal transition (Review)

Zhang,

Hou,

et al. 2024

Int J Oncol

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Since its discovery, the role of the transcription factor, signal transducer and activator of transcription 3 (STAT3), in both normal physiology and the pathology of numerous diseases, including cancer, has been extensively studied. STAT3 is aberrantly activated in different types of cancer, fulfilling a critical role in cancer progression. The biological process, epithelial-mesenchymal transition (EMT), is indispensable for embryonic morphogenesis. During the development of cancer, EMT is hijacked to confer motility, tumor cell stemness, drug resistance and adaptation to changes in the microenvironment. The aim of the present review was to outline recent advances in knowledge of the role of STAT3 in EMT, which may contribute to the understanding of the function of STAT3 in EMT in various types of cancer. Delineating the underlying mechanisms associated with the STAT3-EMT signaling axis may generate novel diagnostic and therapeutic options for cancer treatment. Contents1. Introduction 2. Role of STAT3 signaling in EMT 3. miRNAs and the STAT3-EMT axis 4. lncRNAs and the STAT3-EMT axis 5. circRNAs and the STAT3-EMT axis 6. Targeting the STAT3 pathway in cancer 7. Conclusion

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PROTAC-biomacromolecule conjugates for precise protein degradation in cancer therapy: A review

Wang,

Zhang,

et al. 2024

International Journal of Biological Macromolecules

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Development of decoy oligonucleotide-warheaded chimeric molecules targeting STAT3

Cited by 4 publications

References 19 publications

New-generation advanced PROTACs as potential therapeutic agents in cancer therapy

New-generation advanced PROTACs as potential therapeutic agents in cancer therapy

Role of STAT3 in cancer cell epithelial‑mesenchymal transition (Review)

PROTAC-biomacromolecule conjugates for precise protein degradation in cancer therapy: A review

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