ISR activator 2 

ISR activator 2 is a selective ISR activator. ISR activator 2 can preferentially activate the ISR through the binding of the cytosolic pattern recognition receptor RIG-I, which subsequently activates the heme-regulated inhibitor (HRI) ISR kinase independent of an interferon response. ISR activator 2 can be used for the study of pancreatic cancer^[1].

ISR activator 2 (Compound A8) (10 μM, 8 h) induces the enrichment of UPR (unfolded protein response) and mTORC1 signaling pathway gene sets in HEK293T cells. Further analysis shows that this enrichment was due to increased expression of ISR target genes (such as ASNS, DDIT4, CHAC1 and CHOP)^[1].
ISR activator 2 (16 h) concentration-dependently activates the ATF4-FLuc reporter gene in HEK293T cells stably expressing the ATF4-FLuc reporter gene (EC⁵⁰ = 10.53 μM), and this activation can be blocked by the ISR inhibitor ISRIB (200 nM)^[1].
ISR activator 2 (10 μM, 16 h) activates the ATF4-mAPPLE reporter gene in HEK293T cells stably expressing the ATF4-mAPPLE reporter gene, but HRI knockdown completely blocks this activation, while PERK, GCN2 or PKR knockdown had no effect^[1].
ISR activator 2 (0.625-5 μM) concentration-dependently inhibits the binding of RIG-I to dsRNA probes (K_D = 0.764 μM)^[1].
ISR activator 2 (10 μM, 4 h)-induced increases in CHAC1 and CHOP expression are blocked by RIG-I knockdown^[1].
ISR activator 2 (20 h) concentration-dependently promotes lipid droplet clearance in MEFWT cells and remains effective in ISR-deficient cells (MEFA/A)^[1].
ISR activator 2 (10 μM, 4 h) exhibits separable ISR activation and lipid droplet clearance activities in HEK293T and SW1990 cells through its metabolite CC81^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

451.56

C₂₃H₂₁N₃O₃S₂

332874-88-1

CC1=CC(C)=NC(SCC(NC2=C(C(OCC)=O)C(C3=CC=CC=C3)=CS2)=O)=C1C#N

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• [1]. Cuoco CA, et al. Pharmacological targeting of RIG-I can selectively activate the integrated stress response. Sci Adv. 2025 Oct 31;11(44):eadt3014.  [Content Brief]