DNL343   Click here for help

GtoPdb Ligand ID: 12940

Synonyms: DNL-343
Compound class: Synthetic organic
Comment: DNL343 is an investigational small molecule eIF2B activator [1]. It blocks activation of the integrated stress response (ISR), a biological process that plays a role in driving neurodegeneration in diseases such as ALS/MND and vanishing white matter disease (VWMD). DNL343 was designed to address ISR-mediated neurodegeneration.
The HGNC lists 4 human genes for eIF2B subunits (EIF2B1-EIF2B4).
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 7
Hydrogen bond donors 1
Rotatable bonds 9
Topological polar surface area 81.51
Molecular weight 457.83
XLogP 3.47
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES C1=C(C=CC(=C1)OCC(=O)NC23CC(C2)(C3)C4=NN=C(C5CC(C5)OC(F)(F)F)O4)Cl
Isomeric SMILES C=1C=C(OCC(NC23CC(C=4OC(C5CC(OC(F)(F)F)C5)=NN4)(C2)C3)=O)C=CC1Cl
InChI InChI=1S/C20H19ClF3N3O4/c21-12-1-3-13(4-2-12)29-7-15(28)25-19-8-18(9-19,10-19)17-27-26-16(30-17)11-5-14(6-11)31-20(22,23)24/h1-4,11,14H,5-10H2,(H,25,28)
InChI Key IKPNRMYDOSNVAU-UHFFFAOYSA-N
References
1. Yulyaningsih E, Suh JH, Fanok MH, Chau R, Solanoy H, Takahashi R, Bakardjiev AI, Becerra I, Benitez B, Chiu CL et al.. (2023)
DNL343 is an investigational CNS penetrant eIF2B activator that prevents and reverses the effects of neurodegeneration caused by the Integrated Stress Response.
bioRxiv, Preprint. DOI: 10.1101/2023.08.21.554203