Synonym
DNL343; DNL-343; DNL 343; evetifatorum; evetifator
IUPAC/Chemical Name
2-(4-chlorophenoxy)-N-(3-(5-((1s,3s)-3-(trifluoromethoxy)cyclobutyl)-1,3,4-oxadiazol-2-yl)bicyclo[1.1.1]pentan-1-yl)acetamide
InChi Key
IKPNRMYDOSNVAU-QEJBIBHGSA-N
InChi Code
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)/t11-,14+,18?,19?
SMILES Code
FC(F)(F)O[C@@H]1C[C@H](C2=NN=C(C34CC(C4)(NC(COC5=CC=C(Cl)C=C5)=O)C3)O2)C1
Appearance
To be determined
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 -4 C for short term (days to weeks) or -20 C for long term(months to years).
Solubility
To be determined
Shelf Life
>2 years if stored properly
Drug Formulation
To be determined
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Eukaryotic translation initiation factor 2B (eIF2B) is a key component of the integrated stress response (ISR), which
regulates protein synthesis and stress granule formation in response to cellular insult. Modulation of the ISR has been proposed as a
therapeutic strategy for treatment of neurodegenerative diseases such as vanishing white matter (VWM) disease and amyotrophic
lateral sclerosis (ALS) based on its ability to improve cellular homeostasis and prevent neuronal degeneration.
DNL343 is a small molecule therapy being developed by Denali Therapeutics to treat Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal dementia (FTD). It targets eukaryotic translation initiation factor 2 subunit beta (EIF2B), which is a central regulator of the integrated stress response (ISR). The ISR appears to be overactive in ALS, leading to the formation of stress granules containing TDP-43, which can cause neuronal degeneration. DNL343 prevents and reverses the effects of neurodegeneration caused by the ISR
Preparing Stock Solutions
The following data is based on the
product
molecular weight
457.83
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Yulyaningsih Ernie, Suh Jung H., Fanok Melania H., Chau Roni, Solanoy Hilda, Takahashi Ryan, Bakardjiev Anna I., Becerra Isabel, Benitez N. Butch, Chiu Chi-Lu, Davis Sonnet S, Dowdle William E., Earr Timothy, Estrada Anthony A., Gill Audrey, Ha Connie, Haddick Patrick C. G., Henne Kirk R., Larhammar Martin, Leung Amy Wing-Sze, Maciuca Romeo, Memarzadeh Bahram, Nguyen Hoang N., Nugent Alicia, Osipov Maksim, Ran Yingqing, Rebadulla Kevin, Roche Elysia, Sandmann Thomas, Wang Jing, Lewcock Joseph W., Scearce-Levie Kimberly, Kane Lesley A., Sanchez Pascal E. (2023) DNL343 is an investigational CNS penetrant eIF2B activator that prevents and reverses the effects of neurodegeneration caused by the Integrated Stress Response eLife 12:RP92173
https://doi.org/10.7554/eLife.92173.1
