Results 141 to 150 of about 3,079 (260)

Discovery of a Potent and Selective TEAD Degrader with Durable Degradation Activity

open access: yesAdvanced Science, EarlyView.
KG‐FP‐003, a highly potent TEAD‐YAP PROTAC derived from the patented inhibitor is developed. It selectively degrades endogenous TEAD proteins in HiBiT systems without IMiD‐related off‐target effects. Screening across 867 cancer cell lines revealed broad and superior anti‐tumor activity, highlighting its therapeutic potential through targeted TEAD ...
Linhui Cao   +25 more
wiley   +1 more source

A Replicable and Generalizable Neuroimaging‐Based Indicator of Pain Sensitivity Across Individuals

open access: yesAdvanced Science, EarlyView.
Humans differ in their sensitivity to pain. With six large and diverse fMRI datasets (total N = 1046), this study finds that such individual differences in pain sensitivity can be tracked by fMRI responses to painful stimuli. A highly generalizable machine learning model is further built to predict pain sensitivity across all datasets and analgesic ...
Li‐Bo Zhang   +7 more
wiley   +1 more source

Optimized Monothiol Thioredoxin Derivative (ORP100S) Protects In Vitro and In Vivo from Radiation and Chemotoxicity Without Promoting Tumor Proliferation

open access: yesAdvanced Science, EarlyView.
Native thioredoxin‐1 (TRX) stimulates proliferation and rescues stem cells and cancer cells from multiple stressors by suppressing p53 and inhibiting ferroptosis via GPX4/SLC7A11 upregulation mediated by enhanced KLF4 expression and p53 promoter binding.
Jian Wu   +18 more
wiley   +1 more source

Lactylation of HMGB1 at K177 Drives Nuclear Export of TIAR to Promote Hypoxia‐Induced Stress Granule Formation

open access: yesAdvanced Science, EarlyView.
This study uncovers a novel mechanism in which p300‑catalyzed lactylation of HMGB1 triggers nuclear export of the HMGB1‐TIAR complex, driving TIAR‐dependent SGs formation in the cytoplasm. Mass spectrometry and mutagenesis reveals that K177 lactylation is essential for this export and subsequent SGs formation.
Chengyu Li   +8 more
wiley   +1 more source

Targeting Methylglyoxal Metabolism to Enhance Ferroptosis Sensitivity in Tumor Therapy

open access: yesAdvanced Science, EarlyView.
This study reveals how blocking a detox enzyme called GLO1 increases the buildup of a toxic molecule, methylglyoxal (MGO), which triggers cancer cell death by ferroptosis. A protein called PJA1 drives this process. Targeting the PJA1–GLO1 pathway boosts the effectiveness of ferroptosis‐inducing treatments in tumors, offering a promising approach for ...
Xinyue Zhang   +9 more
wiley   +1 more source

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