Eltanexor (KPT-8602) is an investigational second-generation Selective Inhibitor of Nuclear Export (SINE) compound that is designed to selectively block the nuclear export protein XPO1. Most of the key tumor suppressor proteins (TSPs), are cargos of XPO1 and inhibition of XPO1 by eltanexor is believed to sequester TSPs in the nucleus where they can carry out their normal functions. Karyopharm Therapeutics is developing eltanexor for the treatment of relapsed/refractory cancers.

Sephin1 is a guanabenz derivative that binds to and inhibits a regulatory subunit of the stress-induced protein phosphatase 1 (PPP1R15A), but not the constitutive PPP1R15B, and lacks beta2-adrenergic activity. Phosphorylation of eIF2α, α subunit of eukaryotic translation initiation factor 2, reduces protein synthesis and prevents the accumulation of misfolded protein in the endoplasmic reticulum (ER). PPP1R15A recruits the serine/threonine-protein phosphatase PP1 to dephosphorylate eIF2α, so inhibiting PPP1R15A activity prolongs the phosphorylation of eIF2α and aids in its prevention of the accumulation of misfolded protein. In vitro, Sephin1 protected cells from lethal protein misfolding and cytotoxic ER stress. In vivo Sephin1 prevented Charcot-Marie-Tooth 1B and ALS diseases in mice.