Trial reportClinical and translational science2022
Safety, pharmacokinetics and target engagement of novel RIPK1 inhibitor SAR443060 (DNL747) for neurodegenerative disorders: Randomized, placebo-controlled, double-blind phase I/Ib studies in healthy subjects and patients.
Trial report in Clinical and translational science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 62 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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 Multicenter, Randomized, Placebo-Controlled, Double-Blind, Phase 1b Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL747 in Subjects With Alzheimer's Disease
A Multicenter, Randomized, Placebo-Controlled, Double-Blind, Phase 1b Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL747 in Subjects With Amyotrophic Lateral Sclerosis
Who cites it
62 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.
- Uncovering Necroptosis in Alzheimer's Disease: A Systematic Review of Evidence Across Experimental Models.Cellular and molecular neurobiology · 2025Pooled it
- A Randomized Phase I Trial Evaluating Safety and Pharmacokinetics of Single and Multiple Ascending Doses of Eclitasertib, a RIPK1 Inhibitor, in Healthy Participants.Advances in therapy · 2025Trial
- Safety, Pharmacokinetics and Target Engagement of a Novel Brain Penetrant RIPK1 Inhibitor (SIR9900) in Healthy Adults and Elderly Participants.Clinical and translational science · 2025Trial
- A phase I randomized study to evaluate safety, pharmacokinetics, and pharmacodynamics of SIR2446M, a selective RIPK1 inhibitor, in healthy participants.Clinical and translational science · 2024Trial
- A phase I, randomized, ascending-dose study to assess safety, pharmacokinetics, and activity of GDC-8264, a RIP1 inhibitor, in healthy volunteers.Clinical and translational science · 2023Trial
- A phase I randomized, double-blinded, placebo-controlled study assessing the safety and pharmacokinetics of RIPK1 inhibitor GFH312 in healthy subjects.Clinical and translational science · 2023Trial
- Safety, pharmacokinetics and target engagement of novel RIPK1 inhibitor SAR443060 (DNL747) for neurodegenerative disorders: Randomized, placebo-controlled, double-blind phase I/Ib studies in healthy subjects and patients.Clinical and translational science · 2022Trial
- Necroptosis and the RIPK1-RIPK3-MLKL pathway in chronic kidney disease: mechanisms, crosstalk, and therapeutic opportunities.Renal failure · 2026Review
- RIPK1 Links Metabolic Stresses to Inflammatory and Degenerative Pathways in Alzheimer's Disease.Neuroscience bulletin · 2026Article
- Mechanisms, regulation and clinical relevance of necroptosis.Nature reviews. Molecular cell biology · 2026Review
- CD11c + microglia: From basic research to clinical application.Neural regeneration research · 2026Article
- Review
- The Role of cGAS-STING-Driven PANoptosis in Neurodegenerative Diseases and Therapeutic Prospects.Cells · 2026Review
- Cell Death in Neurodegenerative Diseases: Molecular Mechanisms and Therapeutic Targets.MedComm · 2026Review
- Programmed cell death and metastatic evolution in breast cancer: the role of anoikis, necroptosis, and ferroptosis.Apoptosis : an international journal on programmed cell death · 2026Review
- RIPK 1 in Alzheimer's Disease: Research Progress Integrating Pathogenesis on Necroptosis-Related Neuroinflammation, and Potential Therapeutic Strategies.Biomedicines · 2026Review
- Probing Allosteric Kinase Modulators as Next Game-Changers in Fighting Neurodegeneration.Journal of medicinal chemistry · 2026Review
- Unravelling the role of PANoptosis in diseases: from emerging molecular mechanisms-to-therapeutic implications.Cancer biology & medicine · 2026Review
- Programmed cell death: a promising management for Alzheimer's disease.Apoptosis : an international journal on programmed cell death · 2026Review
- Targeting PANoptosis in atherosclerosis: bridging cell death mechanisms and therapy.Apoptosis : an international journal on programmed cell death · 2026Review
2 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
25 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
RIPK1 is a master regulator of inflammatory signaling and cell death and increased RIPK1 activity is observed in human diseases, including Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS). RIPK1 inhibition has been shown to protect against cell death in a range of preclinical cellular and animal models of diseases. SAR443060 (previously DNL747) is a selective, orally bioavailable, central nervous system (CNS)-penetrant, small-molecule, reversible inhibitor of RIPK1. In three early-stage clinical trials in healthy subjects and patients with AD or ALS (NCT03757325 and NCT03757351), SAR443060 distributed into the cerebrospinal fluid (CSF) after oral administration and demonstrated robust peripheral target engagement as measured by a reduction in phosphorylation of RIPK1 at serine 166 (pRIPK1) in human peripheral blood mononuclear cells compared to baseline. RIPK1 inhibition was generally safe and well-tolerated in healthy volunteers and patients with AD or ALS. Taken together, the distribution into the CSF after oral administration, the peripheral proof-of-mechanism, and the safety profile of RIPK1 inhibition to date, suggest that therapeutic modulation of RIPK1 in the CNS is possible, conferring potential therapeutic promise for AD and ALS, as well as other neurodegenerative conditions. However, SAR443060 development was discontinued due to long-term nonclinical toxicology findings, although these nonclinical toxicology signals were not observed in the short duration dosing in any of the three early-stage clinical trials. The dose-limiting toxicities observed for SAR443060 preclinically have not been reported for other RIPK1-inhibitors, suggesting that these toxicities are compound-specific (related to SAR443060) rather than RIPK1 pathway-specific.
Indexed as
Identifiers
What OpenQuestion holds
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.