ArticleJournal of medicinal chemistry2024
Discovery of KT-474─a Potent, Selective, and Orally Bioavailable IRAK4 Degrader for the Treatment of Autoimmune Diseases.
Article in Journal of medicinal chemistry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed.
- Pharmacokinetics and Pharmacodynamics of KT-474, a Novel Selective Interleukin-1 Receptor-Associated Kinase 4 (IRAK4) Degrader, in Healthy Adults.Clinical and translational science · 2025Trial
- Limiting Trial-and-Error: Linker-Based 2D Descriptor Analysis to Support Very Early Proteolysis-Targeting Chimeras Design.ChemMedChem · 2026Article
- Discovery of Highly Efficacious CRBN-Based KRAS Degraders Targeting Cancers with KRAS G12D and G12V Mutations.Journal of medicinal chemistry · 2026Article
- Nanotechnology-Enabled Targeted Protein Degradation: Strategies, Opportunities, and Challenges.Small methods · 2026Review
- Atopic Dermatitis: New Targets and Emerging Systemic Therapies.American journal of clinical dermatology · 2026Review
- The synthetic landscape of cereblon (CRBN) binders: from thalidomide to emerging chemotypes.Chemical Society reviews · 2026Review
- Innate immunity: current understandings and future perspectives.Signal transduction and targeted therapy · 2026Review
- Safety considerations for cereblon-recruiting targeted protein degraders.Nature reviews. Drug discovery · 2026Review
- Targeted protein degradation: bridging chemical biology and clinical translation.Acta pharmacologica Sinica · 2026Review
- Structural basis for selective and potent degradation of IRAK4 by KT-474.Nature communications · 2026Article
- A unified platform for the rapid assembly of glutarimides for Cereblon E3 ligase modulatory drugs.Nature communications · 2026Article
- First Generation Proteolysis Targeting Chimeras (PROTACs) for the Treatment of Progeria.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Discovery of a paralog-selective p300 protein degrader with potent anti-cancer activity in hematological malignancies.Nature communications · 2026Article
- Discovery of SD-965 as a Potent, Selective, and Efficacious STAT3 PROTAC Degrader.Journal of medicinal chemistry · 2026Article
- PBPK Modelling of PROTACs: Learnings from ARV-110 as a Case Example.The AAPS journal · 2026Article
- Article
- Degraders of the dengue virus capsid protein exhibit differentiated pharmacology relative to capsid inhibitors.Nature communications · 2026Article
- Lessons learned in linking PROTACs from discovery to the clinic.Nature reviews. Chemistry · 2026Review
- A Novel Paradigm for Targeting Challenging Targets: Advancing Technologies and Future Directions of Molecular Glue Degraders.Molecules (Basel, Switzerland) · 2026Review
- Research progress and future perspectives in proteolysis-targeting chimeras.Frontiers in pharmacology · 2026Review
Corrections and comments
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Authors and funding
26 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interleukin-1 receptor associated kinase 4 (IRAK4) is an essential mediator of the IL-1R and TLR signaling pathways, both of which have been implicated in multiple autoimmune conditions. Hence, blocking the activity of IRAK4 represents an attractive approach for the treatment of autoimmune diseases. The activity of this serine/threonine kinase is dependent on its kinase and scaffolding activities; thus, degradation represents a potentially superior approach to inhibition. Herein, we detail the exploration of structure-activity relationships that ultimately led to the identification of KT-474, a potent, selective, and orally bioavailable heterobifunctional IRAK4 degrader. This represents the first heterobifunctional degrader evaluated in a nononcology indication and dosed to healthy human volunteers. This molecule successfully completed phase I studies in healthy adult volunteers and patients with atopic dermatitis or hidradenitis suppurativa. Phase II clinical trials in both of these indications have been initiated.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.