DYR533 / Iluminos - LARVOL DELTA

Targeting Dyrk1a in Alzheimer's Disease: single-nucleus RNA sequencing data reveals broad effects across CNS cell populations (Neuroscience 2026) - "Our group developed a novel inhibitor named DYR533, which reduced neuropathology in three mouse models of ADRD (3xTg-AD, PS19, and Ts65Dn)...These data implicate DYRK1A in AD progression, providing complementary evidence to our findings at the protein level. Cell-specific expression of DYRK1A across disease may provide insight into vulnerable cell classes and how changes impact specific mechanisms driving disease."

Clinical • Alzheimer's Disease • CNS Disorders • Dementia • Movement Disorders • Parkinson's Disease • DYRK1A

Elevated DYRK1A in Primary Tauopathies and Therapeutic Targeting with the Brain-Penetrant Inhibitor DYR533. (PubMed, Res Sq) - "In PS19 mice, DYR533 treatment produced modest improvements on behavior. Together, these findings establish an association between elevated DYRK1A and disease severity in human primary tauopathies and demonstrate that pharmacological inhibition of DYRK1A with DYR533 reduces pathological tau phosphorylation and neuroinflammatory signaling in vivo."

Journal • CNS Disorders • Frontotemporal Lobar Degeneration • Inflammation • Movement Disorders • Progressive Supranuclear Palsy • DYRK1A

Dyrk1a inhibition with the Novel Compound DYR533: A Cross-Disease Therapeutic Strategy Targeting Amyloidosis, Tau Pathogenesis, and Neuroinflammation. (PubMed, bioRxiv) - "We developed DYR533, a selective, orally bioavailable, brain-penetrant Type 1 Dyrk1a kinase inhibitor that also inhibits autophosphorylation and reduces kinase abundance. Across three mouse models (3xTg-AD, PS19, Ts65Dn), DYR533 reduced pathological tau hyperphosphorylation, attenuated neuroinflammation, ameliorated amyloidosis, and improved anxiety-like behavior and spatial memory, collectively supporting Dyrk1a inhibition and DYR533 as a therapeutic strategy for ADRD."

Journal • Alzheimer's Disease • Amyloidosis • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • Inflammation • Mood Disorders • Movement Disorders • Progressive Supranuclear Palsy • Psychiatry • APP

THE THERAPEUTIC POTENTIAL OF DYR533, A NOVEL DYRK1A INHIBITOR, IN SLOWING TAU PATHOGENESIS AND NEUROINFLAMMATION IN FRONTOTEMPORAL DEMENTIA, ALZHEIMER'S DISEASE, AND DOWN SYNDROME. (ADPD 2025) - "Collectively, this work supports the efficacy of DYR533 in mitigating hallmark pathologies and improving neuroinflammation observed in the FTD, AD and DS brain, which may springboard DYR533 for advancement into clinical trials."

Alzheimer's Disease • CNS Disorders • Dementia • Developmental Disorders • Frontotemporal Lobar Degeneration • Genetic Disorders • Inflammation

Validating the efficacy of a novel potent Dyrk1a inhibitor (DYR533) in the Ts65Dn mouse model of Down Syndrome (Neuroscience 2024) - "Collectively, we demonstrate that the optimized small molecule Dyrk1a inhibitor, DYR533, reduces Dyrk1a, Aβ and pTau in the DS Ts65Dn mouse model. This work sets the stage for future development and testing of DYR533 as a potential therapeutic for individuals with DS and AD."

Preclinical • Alzheimer's Disease • CNS Disorders • Aβ42

DYR895: An orally bioavailable, brain penetrant, SMKI toward glioblastoma multiforme and colorectal cancer (ACS-Fall 2024) - "Beginning with DYR533, we tempered selectivity to induce pan-DYRK/CLK activity...As such, in vivo studies have finished in GBM PDX models and orthostatic models of CRC. DYR895 is also clean in a Eurofins Safety Pharmacology panel and is undergoing other mechanism-based safety studies."

Brain Cancer • CNS Tumor • Colorectal Cancer • Gastrointestinal Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor • ABCB1 • CDK7 • CDK9 • EGFR • PDGFRA • PIK3CA

A novel DYRK1a inhibitor, DYR533, reduces tau pathology and TNF alpha in the 3xTg-AD and PS19 mouse models (AAIC 2023) - "In conclusion, the DYRK1a inhibitor, DYR533, reduces pTauSer396, as well as blood plasma and hippocampal levels of Tnf α in both 3xTg-AD and PS19 models. Ongoing efforts include testing the effects of DYR533 in a rodent model of Down syndrome (Ts65Dn), which harbors three copies of DYRK1a , and completion of 3xTg-AD and PS19 experiments. Thus far, these results support DYR533 as a potential therapeutic for AD and the tauopathies."

Preclinical • Alzheimer's Disease • CNS Disorders • Developmental Disorders • Frontotemporal Lobar Degeneration • Genetic Disorders • Oncology • APP • TNFA

Validating the efficacy of a potent DYRK1a Inhibitor (DYR533) in the 3xTg- mouse model of Alzheimer's Disease (Neuroscience 2022) - "Notably, we found a reduction in phosphorylated tau at threonine 217, which was recently shown to be the earliest marker associated with AD progression. Collectively, we demonstrate that the more potent, selective, and orally bioavailable DYRK1a inhibitor (DYR533) reduces Aβ pathology and tau phosphorylation, ultimately paving the way for further clinical development of this candidate AD therapeutic."

Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • APP