DNL343

DNL343 is a brain-penetrating activator of eukaryotic initiation factor 2B (eIF2B) that inhibits the abnormal integrated stress response (ISR). DNL343 inhibits ISR activity 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 has inhibitory potential in studies of vanishing white matter disease (VWMD) driven by eIF2B LOF and chronic ISR activation.


Cat. No.: EX-A8745	Purity: >98%

	Chemical structure of DNL343

For research only, Do not use for Human!

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CAS No.	2278265-85-1
Purity	>98%
Formula	C20H19ClF3N3O4
Mol Weight	457.831
Color	White to light yellow
State	solid powder
Solubility	DMSO : 100 mg/mL
Shelf Life	>3 years if stored properly
Storage	Powder -20°C, 3 years , 4°C, 2 years ; In solvent -20°C, 1 month
Shipping	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.

Reference:	[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.
CoA	CoA of DNL343

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


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