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evetifator   Click here for help

GtoPdb Ligand ID: 12940

Synonyms: DNL-343 | DNL343
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 structure of DNL343 matches that for the INN evetifator (proposed list 131, August 2024).
The HGNC lists 4 human genes for eIF2B subunits (EIF2B1-EIF2B4).

evetifator is commercially available from our sponsors

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 Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). 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

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
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.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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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

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
No information available.
Summary of Clinical Use Click here for help
DNL343 is in clinical development for ALS.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT04297683 HEALEY ALS Platform Trial - Master Protocol Phase 2/Phase 3 Interventional Massachusetts General Hospital
NCT05842941 HEALEY ALS Platform Trial - Regimen G DNL343 Phase 2/Phase 3 Interventional Massachusetts General Hospital
NCT04268784 A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL343 in Healthy Volunteers Phase 1 Interventional Denali Therapeutics Inc.