D. K. Nomura

DCAF16-Based Covalent Handle for the Rational Design of Monovalent Degraders

This study identifies a covalent handle that enables the degradation of multiple protein targets when appended to protein-targeting ligands.

Covalent 14-3-3 Molecular Glues and Heterobifunctional Molecules Against Nuclear Transcription Factors and Regulators

This study identifies a covalent ligand, EN171, that enhances 14-3-3 interactions with transcription factors like ER, YAP, and TAZ, inhibiting their activity and demonstrating its use in heterobifunctional molecules to sequester nuclear substrates.

Covalent Degrader of the Oncogenic Transcription Factor β-Catenin

This paper identifies a covalent degrader, EN83, that targets and degrades β-catenin by covalently binding to four cysteine residues, demonstrating a strategy to overcome the 'undruggable' challenge of transcription factors.

Targeted Protein Degradation through Recruitment of the CUL4A Complex Adaptor Protein DDB1

This study identifies a covalent recruiter targeting DDB1 for PROTAC applications, enabling degradation of BRD4 and androgen receptor.

Covalent Targeting of Glutamate Cysteine Ligase to Inhibit Glutathione Synthesis

This study identifies a covalent inhibitor EN25 that targets GCLM to inhibit glutathione synthesis in ARID1A-deficient cancer cells.

Ophiobolin A Covalently Targets Complex IV Leading to Mitochondrial Metabolic Collapse in Cancer Cells

This study identifies Ophiobolin A's covalent targets in complex IV of mitochondria, revealing a mechanism of metabolic collapse and cell death in cancer cells.

Chemoproteomic Profiling Reveals that Anti-Cancer Natural Product Dankastatin B Covalently Targets Mitochondrial VDAC3

This study identifies dankastatin B as a covalent inhibitor of VDAC3 in breast cancer cells, revealing its mechanism of action through chemoproteomic profiling.

Targeted Protein Degradation through E2 Recruitment

This study identifies a covalent recruiter for the E2 ubiquitin conjugating enzyme UBE2D, enabling targeted protein degradation via PROTACs.

Rational Chemical Design of Molecular Glue Degraders

This paper develops a strategy to convert protein-targeting ligands into molecular glue degraders by identifying a covalent handle that induces proteasome-mediated degradation of target proteins.

X chromosome dosage drives statin-induced dysglycemia and mitochondrial dysfunction

This study identifies X chromosome dosage and DHA reduction as drivers of statin-induced dysglycemia and mitochondrial dysfunction in females.

Chemoproteomics-Enabled Discovery of a Covalent Molecular Glue Degrader Targeting NF-κB

This study identifies a covalent molecular glue degrader, EN450, that induces the degradation of NFKB1 via a ternary complex with UBE2D, leading to anti-proliferative effects in leukemia cells.

Discovery of Potent Pyrazoline-Based Covalent SARS-CoV-2 Main Protease Inhibitors

This study identifies and optimizes potent pyrazoline-based covalent inhibitors of SARS-CoV-2 Mpro, showing activity against multiple coronaviruses.

Fasting Induces a Highly Resilient Deep Quiescent State in Muscle Stem Cells via Ketone Body Signaling

This study shows that fasting induces a deep quiescent state in muscle stem cells through ketone body signaling, enhancing their resilience to stress.

Deubiquitinase-Targeting Chimeras for Targeted Protein Stabilization

This paper introduces the DUBTAC platform for targeted protein stabilization by linking a covalent OTUB1 recruiter to lumacaftor, demonstrating stabilization of ΔF508-CFTR in human cells.

Discovery of a Covalent FEM1B Recruiter for Targeted Protein Degradation Applications

The paper discovers a covalent ligand, EN106, that targets FEM1B for PROTAC-based protein degradation, demonstrating its utility in degrading BRD4.

Mitohormesis reprograms macrophage metabolism to enforce tolerance

This paper shows that mitochondrial stress from mtROS and mtRES triggers mitohormesis in macrophages, leading to tolerance by suppressing proinflammatory gene transcription.

A Nimbolide-Based Kinase Degrader Preferentially Degrades Oncogenic BCR-ABL

This paper develops a PROTAC molecule, BT1, that selectively degrades BCR-ABL over c-ABL in leukemia cells using nimbolide as an E3 ligase recruiter, showing additional anti-proliferative effects.

Adhesion-mediated mechanosignaling forces mitohormesis

The paper shows that adhesion-mediated mechanosignaling activates a mitochondrial stress response through SLC9A1 and HSF1, altering mitochondrial function in aging and cancer.

Manumycin Polyketides Act as Molecular Glues Between UBR7 and P53 to Impair Breast Cancer Pathogenicity

The paper identifies manumycin polyketides as molecular glues that bind UBR7 and P53, impairing breast cancer pathogenicity through p53 activation and cell death.

Harnessing the Anti-Cancer Natural Product Nimbolide for Targeted Protein Degradation

This study identifies nimbolide's mechanism of action by showing it targets RNF114, leading to stabilization of p21 and inhibition of breast cancer cell proliferation.

Parthenolide Covalently Targets and Inhibits Focal Adhesion Kinase in Breast Cancer Cells

This study identifies parthenolide's covalent targeting of FAK1 in breast cancer cells, showing inhibition of FAK1-dependent pathways and cancer cell proliferation.

A metabolic dependency for host isoprenoids in the obligate intracellular pathogen Rickettsia parkeri underlies a sensitivity for the statin class of host-targeted therapeutics

This study identifies a metabolic dependency of Rickettsia parkeri on host isoprenoids, showing that statin drugs inhibit bacterial growth by disrupting cell wall synthesis.

Covalent Ligand Screening Uncovers a RNF4 E3 Ligase Recruiter for Targeted Protein Degradation Applications

This study identifies a covalent ligand for RNF4, an E3 ligase, and demonstrates its use in designing a bifunctional degrader that effectively degrades BRD4.

Estrogen Signaling in Arcuate Kiss1 Neurons Suppresses a Sex-Dependent Circuit That Promotes Dense Strong Bones in Female Mice

This study identifies estrogen signaling in arcuate Kiss1 neurons as a key regulator of sex-dependent bone density in female mice, revealing a novel neuroskeletal pathway.