Table 2 UPR modulating drugs in GBM.

Molecules used in GBM models and reported to act through the modulation of ER proteostasis. HSP72, heat shock protein 72; Hsc70, heat shock cognate 70.

ModelDrug nameLink to ER stressCellular impactClinical
trial
(yes/no)
Reference
In vivoHuman
cell lines
2,5-Dimethyl-celecoxibGRP78 and CHOP inductionApoptosis inductionNo(151)
Δ9-TetrahydrocannabinolATF4, CHOP, and TRB3 induction and
eIF2α phosphorylation
Apoptosis induction, reduced
tumor growth, and autophagy
Yes(152, 153)
Asiatic acid (2,3,23-trihydroxy-
12-ursen-28-oic acid, C30H48O5)
GRP78 and calpain induction,
calnexin and IRE1α down-regulation
Cell death inductionNo(154)
Epigallocatechin 3-gallate + TMZGRP78 down-regulationIncreased mice survival and
increased glioma cell
sensitivity to TZM
No(22, 155)
NEO212 (TMZ conjugated to
perillyl alcohol)
CHOP inductionCell death inductionNo(156)
Perillyl alcoholGRP78, ATF3, and CHOP inductionCytotoxicity and decreased
invasion
Yes(157, 158)
PiperlongumineCHOP, eIF2a, ATF4, GADD34, and
GRP78 induction
ROS-induced cell deathNo(159)
In vitroPrimariesRDC11GRP78 and CHOP
induction, and
XBP1 splicing
DNA damage and apoptosis
induction, and cell growth
inhibition
No(66)
TMZ + chloroquineCHOP inductionAutophagy inhibition and
apoptosis induction
No(160)
2-Amino-N-{4-[5-(2-phenanthrenyl)-3-
(trifluoromethyl)-1H-pyrazol-1-yl]-phenyl}
acetamide (OSU-03012)
Involvement of GRP78 and
PERK pathways
Cell death inductionNo(161)
Celecoxib + sildenafileIF2α phosphorylation and
activation of ATF4/CHOP pathway
Autophagy and cell death
induction
No(162)
Terpyridineplatinum(II) complexesGRP78 inductionPerturbation of redox metabolism
and cell cycle arrest
No(163)
Human cell
lines
TMZ + SKI-II (4-((4-(4-chlorophenyl)-
2-thiazolyl)amino)phenol)
GRP78 and CHOP inductionROS-induced cell deathNo(164)
Withaferin AGRP78, IRE1, and CHOP inductionROS production and apoptosis
induction
No(165)
2-Deoxy-d-glucoseER stress response gene signatureIL-8 inductionNo(166)
2-Deoxy-d-glucose + cisplatinGRP78 inductionAutophagy inhibitionNo(167)
2-Hydroxyoleic acidIRE1α, CHOP, and ATF4 induction,
XBP1 splicing, and eIF2α
phosphorylation
Cell cycle arrest and autophagy
induction
No(168)
5-Androstene 3β,17α diol (17α-AED)GRP78 and CHOP induction, and
activation of PERK/eIF2α signaling
Autophagy inductionNo(169)
Amiodarone + TRAILCHOP inductionApoptosis inductionNo(170)
Antp-TPR hybrid peptideGRP78 and CHOP inductionCell death and cytotoxicity
induction
No(171)
BerberineGRP78, CHOP, and PERK induction,
and eIF2α phosphorylation
Apoptosis induction and ROS
generation
No(172, 173)
BufalinGRP78 and CHOP induction, and PERK and
eIF2α phosphorylation
Apoptosis and autophagy
induction
No(174)
Candidaspongiolide (CAN)Activation of PERK/eIF2α signalingApoptosis induction and protein
synthesis inhibition in normal cells
No(175)
CelastolHSP72 and HSP90 inductionAutophagy induction and
accumulation of protein aggregates
No(176)
Celecoxib + γ-irradiationCHOP inductionCell cycle arrest and autophagy
induction under hypoxia
Yes(177)
Celecoxib/2,5-dimethyl-celecoxib + bortezomibGRP78 and CHOP inductionApoptosis inductionNo(65)
Copper (Cu)GRP78 induction and aggregationROS generationNo(178)
Cyano enone of methyl boswellatesActivation of IRE1α and PERKApoptosis inductionNo(179)
Fatsioside APERK and eIF2α phosphorylation,
and CHOP induction
Apoptosis inductionNo(180)
FluoxetineActivation of PERK/eIF2α/ATF4 and
ATF6/CHOP signaling
Apoptosis inductionNo(181)
GlucosamineGRP78, IRE1α, and eIF2α inductionAutophagic cell death inductionNo(182)
Nelfinavir/atazanavirInduction of GRP78, CHOP, and
PERK/eIF2α/ATF4 activation
Cell death induction and
accumulation of protein aggregates
(misfolding)
Yes(22, 67)
Minocycline (7-dimethylamino-6-
desoxytetracycline; Mino)
PERK/eIF2α/CHOP and IRE1
activation, XBP1 splicing, and GRP78
induction
Apoptosis and autophagy
induction
No(184)
Phenethyl isothiocyanateGRP78, CHOP, XBP1, IRE1α,
and calpain 1 and 2 induction
Apoptosis induction, decreased
migration and invasion, and cell
cycle arrest
No(185187)
Polyether ionophore antibiotics
(monensin, salinomycin, nigericin, narasin,
and lasalocid A)
CHOP and ATF4 induction, and
eIF2a phosphorylation
TRAIL-mediated apoptosisNo(188)
Prenyl-phloroglucinol derivative
[2,4-bis(4-fluorophenylacetyl)phloroglucinol]
GRP78, GRP94, IRE1, and CHOP
induction, and eIF2α
phosphorylation
ROS generation and apoptosis
induction
No(189)
Quinine, quinacrine, mefloquine,
and hydroxychloroquine
CHOP inductionApoptosis inductionNo(190)
S1 (BH3 mimetics)GRP78 and CHOP induction, and
IRE1 activation
Apoptosis and autophagy
induction
No(191)
Schweinfurthin analogseIF2α phosphorylation and GRP78
induction
Inhibition of cancer growth and
apoptosis induction
No(192)
Sulindac sulfideGRP78 inductionCell death inductionNo(193)
TMZCHOP inductionNo(22)
Unsaturated fatty acids + irradiationGRP78 inductionIncreased radiosensitivity and cell
death induction
No(194)
Zoledronic acidIRE1 inductionApoptosis inductionNo(195)
Other cell
lines
Ursolic acidActivation of PERK/eIF2α/CHOP and
IRE1/JNK pathway
Apoptosis and autophagy
induction
No(196)
ValproateGRP78, GRP94, calreticulin, and
CHOP induction
Inhibition of proliferationNo(197, 198)
WogoninGRP78 induction and eIF2α
phosphorylation
ROS production and apoptosis
induction
No(199)
YessotoxineIF2α and PERK phosphorylation,
and XBP1 splicing
Cell cycle arrest and protein
synthesis inhibition
No(200)
CarbamazepineGRP78 inductionUnknownNo(201)
Cyclosporine AIRE1α and PERK phosphorylation,
and GRP78 and CHOP induction
Apoptosis and autophagy
induction
No(202, 203)
DesipramineActivation of PERK/eIF2α and ATF6
signaling, and CHOP induction
Autophagy and apoptosis
induction
No(204, 205)
EthanolHsc70, GRP78, and GRP94 inductionUnknownNo(206, 207)
Lead (Pb acetate)Modulates GRP78 mRNAUnknownNo(208, 209)
Mercury (HgCl2)Increased GRP78 protein expressionOxidative stress modulationNo(209)
Oleyl glucosaminide derivativeGRP78, CHOP, p8, and RAPM4
induction
Cell death inductionNo(210)
Sesquiterpene coumarin DAW22GRP78 and CHOP induction, and
PERK, ATF6, and IRE1 activation
Apoptosis inductionNo(211)