DNL343

DNL343 is a potent, selective, orally active and brain-penetrant activator of eukaryotic initiation factor eIF2B. DNL343 inhibits the activity of the integrated stress response (ISR) in the central nervous system (CNS) and reverses neurodegeneration and neuroinflammation. DNL343 also prevents motor dysfunction and premature death in eIF2B loss-of-function (LOF) mutant mice. DNL343 can be used in the study of neurodegenerative diseases[1][2][3].

Product Specifications

CAS Number

[2278265-85-1]

UNSPSC

12352005

Target

Eukaryotic Initiation Factor (eIF)

Type

Reference compound

Related Pathways

Cell Cycle/DNA Damage

Applications

Neuroscience-Neuromodulation

Field of Research

Neurological Disease

Assay Protocol

https://www.medchemexpress.com/dnl343.html

Concentration

10mM

Purity

99.94

Solubility

DMSO : 100 mg/mL (ultrasonic)

Smiles

ClC(C=C1)=CC=C1OCC(NC23CC(C3)(C4=NN=C([C@@H]5C[C@@H](C5)OC(F)(F)F)O4)C2)=O

Molecular Formula

C20H19ClF3N3O4

Molecular Weight

457.83

References & Citations

[1]Yulyaningsih E, et al. DNL343 is an investigational CNS penetrant eIF2B activator that prevents and reverses the effects of neurodegeneration caused by the Integrated Stress Response[J]. bioRxiv, 2023: 2023.8.21.554203|[2]Craig R A, et al. Discovery of DNL343: A Potent, Selective, and Brain-Penetrant eIF2B Activator Designed for the Treatment of Neurodegenerative Diseases[J]. Journal of Medicinal Chemistry, 2024, 67 (7) : 5758-5782.|[3]Yulyaningsih E, et al. DNL343 is an investigational CNS penetrant eukaryotic initiation factor 2B activator that prevents and reverses the effects of neurodegeneration caused by the integrated stress response[J]. Elife, 2024, 12: RP92173.