Table 1.

Drugs targeting the Unfolded Protein Response

Therapeutic	Mechanism	Indication	Ref
PERK arm
Salubrinal	eIF2α -phosphorylation inhibitor	AD, ALS, HD, PD	(28, 56)
Guanabenz	Inhibitor of eIF2α phosphatase	AD, ALS, HD	(69, 70)
GSK265157/GSK2606414	PERK kinase inhibitor	AD, ALS, HD	(60, 62)
ISRIB	Inhibitor of eIF2α phosphatase	Prion disease	(64, 65)
Sephin1	Inhibitor of eIF2α phosphatase	ALS	(71)
AMG PERK 44	PERK kinase inhibitor	Not tested	(66)
IRE1α arm
STF-083010	IRE1α RNase active site inhibitor	AD, ALS, HD models	(73)
MKC-3946	IRE1α RNase active site inhibitor	AD, ALS, HD models	(72)
4u8C	IRE1α RNase active site inhibitor	AD, ALS, HD models	(72)
KIRA6	IRE1α type II kinase inhibitor	Other models	(74)
OICR464	Binds to the RNase domain of murine IRE1	Not tested	(74)
OICR573	Binds to the RNase domain of murine IRE1	Not tested	(74)
ATF6 arm
Apigenin	Up regulation of ATF 6 expression	PD, AD	(75, 77)
Baicalein	Up regulation of ATF 6 expression	PD	(76)
Kaempferol	Down regulation of ATF 6 expression	AD	(221)
Chemical chaperones
4-phenylbutyrate (4-PBA)	Stabilizes misfolded/unfolded proteins	AD, ALS, HD	(78, 79)
Tauroursodeoxycholic acid (TUDCA)	Stabilizes misfolded/unfolded proteins	AD, ALS, HD	(80, 81)
Miscellaneous
Arimoclomol	Co-inducer of heat shock response	ALS	(83)
Celastrol	Co-inducer of heat shock response	AD, ALS	(84, 85)
Tanespimycin	Co-inducer of heat shock response	AD, ALS	(86)
PRE-084	Sigma-1 receptor agonist	AD, HD, ALS	(82)
SA4503	Sigma-1 receptor agonist	ALS	(82)