Endoplasmic Reticulum Stress: Its Role in Disease and Novel Prospects for Therapy

Table 2

Compounds with potency to ameliorate ER stress.

Compound	Target/effect	References
Chemical chaperones (TUDCA, 4-PBA)	(i) Increased protein folding capacity; (ii) Increased ERAD efficiency; (iii) Minimized caspase activation	[129, 338–343]
Inducers of chaperone activity (lithium, valproate, BIX)	(i) Increased expression and activity of chaperones; (ii) Supportive of cell-protective ER stress mechanism	[344–350]
Benzodiazepines	(i) Inhibition of ASK1 function and IRE1-ASK1 signaling; (ii) Obstructive to pro-apoptotic ER stress mechanism	[88]
Inhibitors of eIF2-alpha phosphatase (salubrinal, Guanabenz)	(i) Inhibition of PP1/GADD34 phosphatase activity; (ii) Supportive of attenuated global protein synthesis	[351–353]
Antioxidants (BHA, TM2002, and baicalein)	(i) Sequestration of free radicals; (ii) Reduction of oxidative stress and apoptosis	[354–357]
Inducers of antioxidant pathways (carnosic acid, triterpenoids)	(i) Stimulation of NRF2 pathway; (ii) Protection from oxidative stress and resulting apoptosis	[358–363]
Stress kinase inhibitors (JNK or p38 inhibitors)	(i) Inhibition of pro-apoptotic JNK or p38 pathways; (ii) Antagonism to pro-apoptotic CHOP function	[354, 364–367]

BHA: butylated hydroxyanisole.
BIX: BiP/GRP78 inducer X (1-(3,4-dihydroxyphenyl)-2-thiocyanate-ethanone).
4-PBA: 4-phenyl butyric acid.
TUDCA: tauroursodeoxycholic acid.