Trial reportNature medicine2023
IRAK4 degrader in hidradenitis suppurativa and atopic dermatitis: a phase 1 trial.
Trial report in Nature medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04772885 (A Phase 1 Randomized, Placebo-controlled, Single and Multiple Ascending Dose Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Orally Administered KT-474 in Healthy Adult Volunteers and Patients With Atopic Dermatitis), which is not on this map. Cited by 60 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 1 Randomized, Placebo-controlled, Single and Multiple Ascending Dose Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Orally Administered KT-474 in Healthy Adult Volunteers and Patients With Atopic Dermatitis (AD) or Hidradenitis Suppurativa (HS)
Who cites it
60 citing papers in PubMed, 102 citations in OpenAlex.
- 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
- The oral IRAK4 inhibitors zabedosertib and BAY1830839 suppress local and systemic immune responses in a randomized trial in healthy male volunteers.Clinical and translational science · 2024Trial
- A Novel Assay Platform for Targeted Protein Degradation Monitoring: Case Study of Antibody Free Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) for MALT1 Target Quantification.The AAPS journal · 2026Article
- Atopic Dermatitis: New Targets and Emerging Systemic Therapies.American journal of clinical dermatology · 2026Review
- Review
- Machine Learning-Driven Drug Repositioning Identifies Putative IRAK4 Inhibitors Through Structure-Based Computational Evaluation.Current issues in molecular biology · 2026Article
- Contemporary design of small-molecule kinase modulators: orthosteric, allosteric and induced-proximity strategies.Nature reviews. Drug discovery · 2026Review
- Safety considerations for cereblon-recruiting targeted protein degraders.Nature reviews. Drug discovery · 2026Review
- Kinetic control of macrophage death by PTM-turnover crosstalk in infection and inflammation.Cell chemical biology · 2026Review
- PROTAC-mediated regulation of programmed cell death: From molecular mechanisms to therapeutic breakthroughs.Innovation (Cambridge (Mass.)) · 2026Review
- The expanding role of formulations to enable oral delivery of poorly water-soluble drugs.Nature reviews. Drug discovery · 2026Review
- Structural basis for selective and potent degradation of IRAK4 by KT-474.Nature communications · 2026Article
- Clinical Breakthrough in Targeted Protein Degradation: Reflections on the Approval of ARV-471.Cancer innovation · 2026Article
- A phenotype-to-mechanism framework links phenome-wide comorbidity architecture to molecular mechanisms and therapeutic discovery in complex diseases.medRxiv : the preprint server for health sciences · 2026Article
- Peptide-Based PROTACs: Transitioning from Static Paradigm to a Dynamic Landscape within Targeted Protein Degradation.Bioconjugate chemistry · 2026Review
- Mechanisms and Design Principles of Proteolysis-Targeting Chimeras and Their Emerging Applications.ACS pharmacology & translational science · 2026Review
- Structural dynamics of the midnolin-proteasome during ubiquitin-independent substrate turnover.Nature communications · 2026Article
- PBPK Modelling of PROTACs: Learnings from ARV-110 as a Case Example.The AAPS journal · 2026Article
- Induced proximity-based therapeutic modalities.Nature reviews. Drug discovery · 2026Review
- Lessons learned in linking PROTACs from discovery to the clinic.Nature reviews. Chemistry · 2026Review
Corrections and comments
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Authors and funding
31 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Toll-like receptor-driven and interleukin-1 (IL-1) receptor-driven inflammation mediated by IL-1 receptor-associated kinase 4 (IRAK4) is involved in the pathophysiology of hidradenitis suppurativa (HS) and atopic dermatitis (AD). KT-474 (SAR444656), an IRAK4 degrader, was studied in a randomized, double-blind, placebo-controlled phase 1 trial where the primary objective was safety and tolerability. Secondary objectives included pharmacokinetics, pharmacodynamics and clinical activity in patients with moderate to severe HS and in patients with moderate to severe AD. KT-474 was administered as a single dose and then daily for 14 d in 105 healthy volunteers (HVs), followed by dosing for 28 d in an open-label cohort of 21 patients. Degradation of IRAK4 was observed in HV blood, with mean reductions after a single dose of ≥93% at 600-1,600 mg and after 14 daily doses of ≥95% at 50-200 mg. In patients, similar IRAK4 degradation was achieved in blood, and IRAK4 was normalized in skin lesions where it was overexpressed relative to HVs. Reduction of disease-relevant inflammatory biomarkers was demonstrated in the blood and skin of patients with HS and patients with AD and was associated with improvement in skin lesions and symptoms. There were no drug-related infections. These results, from what, to our knowledge, is the first published clinical trial using a heterobifunctional degrader, provide initial proof of concept for KT-474 in HS and AD to be further confirmed in larger trials. ClinicalTrials.gov identifier: NCT04772885 .
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Registered trials
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.