A Covalent PFKL Activator Suppresses Tumor Growth Article Swipe
Xiaoding Jiang
,
Eric M. Lynch
,
Congcong Lyu
,
Crystal N. Wilson
,
Lauren E. Salay
,
Scott K. Lyons
,
Mu‐Jie Lu
,
Shuangyu Luo
,
Gibae Kim
,
Hsin‐Ru Chan
,
Walter G. Wolfe
,
Yi‐Chih Lin
,
Justin M Kollman
,
Xiaolu A. Cambronne
,
Ku‐Lung Hsu
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.10.02.680014
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.10.02.680014
Glycolysis fuels vital cellular functions and its dysregulation is implicated in cancer, neurodegeneration, antibiotic resistance and diabetes. The glycolytic dependency of cancer, known as the Warburg effect, presents a key vulnerability for developing targeted anticancer agents but remains challenging due to metabolic heterogeneity and resistance. Here, we developed a first-in-class covalent phosphofructokinase-1 liver type (PFKL) activator that induces metabolic imbalance coupled to delivery of a cytotoxic payload to cancer cells in vitro and in vivo. The electrophile-drug conjugate (EDC) site-specifically and proteome-wide selectively modifies K677 in the allosteric effector site to stabilize the R-state tetramer of PFKL and destabilize cell metabolism. We introduce EDCs as a new delivery mechanism analogous to antibody-drug conjugates but differentiated by selective covalent targeting of intracellular proteins.
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- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2025.10.02.680014
- https://www.biorxiv.org/content/biorxiv/early/2025/10/03/2025.10.02.680014.full.pdf
- OA Status
- green
- OpenAlex ID
- https://openalex.org/W4414808041
All OpenAlex metadata
Raw OpenAlex JSON
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A Covalent PFKL Activator Suppresses Tumor GrowthWork title
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preprintOpenAlex work type
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enPrimary language
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2025Year of publication
- Publication date
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2025-10-03Full publication date if available
- Authors
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Xiaoding Jiang, Eric M. Lynch, Congcong Lyu, Crystal N. Wilson, Lauren E. Salay, Scott K. Lyons, Mu‐Jie Lu, Shuangyu Luo, Gibae Kim, Hsin‐Ru Chan, Walter G. Wolfe, Yi‐Chih Lin, Justin M Kollman, Xiaolu A. Cambronne, Ku‐Lung HsuList of authors in order
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https://doi.org/10.1101/2025.10.02.680014Publisher landing page
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https://www.biorxiv.org/content/biorxiv/early/2025/10/03/2025.10.02.680014.full.pdfDirect link to full text PDF
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-
YesWhether a free full text is available
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-
greenOpen access status per OpenAlex
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https://www.biorxiv.org/content/biorxiv/early/2025/10/03/2025.10.02.680014.full.pdfDirect OA link when available
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0Total citation count in OpenAlex
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