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2000
Volume 32, Issue 13
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X

Abstract

Background

Integrated Stress Response Inhibitor (ISRIB) works by inhibiting the integrated stress response, a cellular pathway involved in the regulation of protein synthesis during stress conditions. Conditions that have been studied or suggested as potential candidates for treatment with ISRIB include neurological and metabolic disorders, cognitive impairment, viral infections, and cancer.

Objective

The study aimed to discuss the challenges related to specificity, long-term safety, and disease-specific considerations crucial for realizing the full potential of ISRIB.

Methods

A narrative review of the literature has been conducted to delve into ISRIB's chemistry, mechanisms of action, disease-specific considerations, and long-term safety implications.

Results

While ISRIB has shown promising results in preclinical studies, more research is needed to determine its safety and effectiveness in human patients. Clinical trials are required to validate its therapeutic potential for various conditions. Despite having been proposed a decade ago, news of its clinical trials has been circulated only recently, without any published information yet and with rumors that its efficacy safety profile may be compromised by side effects.

Conclusion

While ISRIB offers exciting prospects for a range of biomedical applications, addressing challenges related to specificity, disease-specific considerations, and importantly long-term safety, is crucial for realizing its full potential.

© 2025 Bentham Science Publishers
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References

  1. SidrauskiC. Acosta-AlvearD. KhoutorskyA. VedanthamP. HearnB.R. LiH. GamacheK. GallagherC.M. AngK.K.H. WilsonC. OkreglakV. AshkenaziA. HannB. NaderK. ArkinM.R. RensloA.R. SonenbergN. WalterP. Pharmacological brake-release of mRNA translation enhances cognitive memory.eLife20132e0049810.7554/eLife.0049823741617
     [Google Scholar]
  2. molview, org.MolView.2014Available From: Molview. org/?cid=1011240
  3. NutraBiotechcChemMemory-enhancing ISRIB to help you achieve your Brain goals.2014Available From: www.nutrabiotechchem.com/trans-ISRIB/
  4. Selleck ChemicalsISRIB (trans-isomer).2015Available From: www.selleckchem.com/products/isrib-trans-isomer.html
  5. ParkG. XuK. CheaL. KimK. SafartaL. SongK.H. WuJ. ParkS. MinH. HiramatsuN. HanJ. LinJ.H. Neurodegeneration risk factor, EIF2AK3 (PERK), influences tau protein aggregation.J. Biol. Chem.2023299210282110.1016/j.jbc.2022.10282136563857
     [Google Scholar]
  6. JinS. CojocariD. PurkalJ.J. PopovicR. TalatyN.N. XiaoY. SolomonL.R. BoghaertE.R. LeversonJ.D. PhillipsD.C. 5-Azacitidine induces NOXA to prime AML cells for venetoclax-mediated apoptosis.Clin. Cancer Res.202026133371338310.1158/1078‑0432.CCR‑19‑190032054729
     [Google Scholar]
  7. WangJ. HuB. ZhaoZ. ZhangH. ZhangH. ZhaoZ. MaX. ShenB. SunB. HuangX. HouJ. XiaQ. Intracellular XBP1-IL-24 axis dismantles cytotoxic unfolded protein response in the liver.Cell Death Dis.20201111710.1038/s41419‑019‑2209‑631907348
     [Google Scholar]
  8. XieS.Z. Garcia-PratL. VoisinV. FerrariR. GanO.I. WagenblastE. KaufmannK.B. ZengA.G.X. TakayanagiS. PatelI. LeeE.K. JargstorfJ. HolmesG. RommG. PanK. ShoongM. VediA. LubertoC. MindenM.D. BaderG.D. LaurentiE. DickJ.E. Sphingolipid modulation activates proteostasis programs to govern human hematopoietic stem cell self-renewal.Cell Stem Cell2019255639653.e710.1016/j.stem.2019.09.00831631013
     [Google Scholar]
  9. MiaoL. YuanY. ChengF. FangJ. ZhouF. MaW. JiangY. HuangX. WangY. ShanL. ChenD. ZhangJ. Translation repression by maternal RNA binding protein Zar1 is essential for early oogenesis in zebrafish.Development2017144112813827913641
     [Google Scholar]
  10. BriggsD.I. DefensorE. Memar ArdestaniP. YiB. HalpainM. SeabrookG. ShamlooM. Role of endoplasmic reticulum stress in learning and memory impairment and Alzheimer’s disease-like neuropathology in the PS19 and APPSwe mouse models of tauopathy and amyloidosis.eNeuro201744201710.1523/ENEURO.0025‑17.201728721361
     [Google Scholar]
  11. Pakos-ZebruckaK. KorygaI. MnichK. LjujicM. SamaliA. GormanA.M. The integrated stress response.EMBO Rep.201617101374139510.15252/embr.20164219527629041
     [Google Scholar]
  12. SidrauskiC. McGeachyA.M. IngoliaN.T. WalterP. The small molecule ISRIB reverses the effects of eIF2α phosphorylation on translation and stress granule assembly.eLife20154e0503310.7554/eLife.0503325719440
     [Google Scholar]
  13. KrukowskiK. NolanA. FriasE.S. BooneM. UretaG. GrueK. PaladiniM.S. ElizarrarasE. DelgadoL. BernalesS. WalterP. Small molecule cognitive enhancer reverses age-related memory decline in mice.Elife20209e620410.7554/eLife.62048
     [Google Scholar]
  14. Costa-MattioliM. WalterP. The integrated stress response: From mechanism to disease.Science20203686489eaat531410.1126/science.aat531432327570
     [Google Scholar]
  15. SharmaV. SoodR. KhlaifiaA. EslamizadeM.J. HungT.Y. LouD. AsgarihafshejaniA. LalzarM. KiniryS.J. StokesM.P. CohenN. NelsonA.J. AbellK. PossematoA.P. Gal-Ben-AriS. TruongV.T. WangP. YiannakasA. SaffarzadehF. CuelloA.C. NaderK. KaufmanR.J. Costa-MattioliM. BaranovP.V. QuintanaA. SanzE. KhoutorskyA. LacailleJ.C. RosenblumK. SonenbergN. eIF2α controls memory consolidation via excitatory and somatostatin neurons.Nature2020586782941241610.1038/s41586‑020‑2805‑833029011
     [Google Scholar]
  16. ZyryanovaA.F. WeisF. FailleA. AlardA.A. Crespillo-CasadoA. SekineY. HardingH.P. AllenF. PartsL. FromontC. FischerP.M. WarrenA.J. RonD. Binding of ISRIB reveals a regulatory site in the nucleotide exchange factor eIF2B.Science201835963831533153610.1126/science.aar512929599245
     [Google Scholar]
  17. TsaiJ.C. Miller-VedamL.E. AnandA.A. JaishankarP. NguyenH.C. RensloA.R. FrostA. WalterP. Structure of the nucleotide exchange factor eIF2B reveals mechanism of memory-enhancing molecule.Science20183596383eaaq093910.1126/science.aaq093929599213
     [Google Scholar]
  18. SekineY. ZyryanovaA. Crespillo-CasadoA. FischerP.M. HardingH.P. RonD. Mutations in a translation initiation factor identify the target of a memory-enhancing compound.Science201534862381027103010.1126/science.aaa698625858979
     [Google Scholar]
  19. HallidayM. RadfordH. SekineY. MorenoJ. VerityN. le QuesneJ. OrtoriC.A. BarrettD.A. FromontC. FischerP.M. HardingH.P. RonD. MallucciG.R. Partial restoration of protein synthesis rates by the small molecule ISRIB prevents neurodegeneration without pancreatic toxicity.Cell Death Dis.201563e1672e167210.1038/cddis.2015.4925741597
     [Google Scholar]
  20. PalamL.R. GoreJ. CravenK.E. WilsonJ.L. KorcM. Integrated stress response is critical for gemcitabine resistance in pancreatic ductal adenocarcinoma.Cell Death Dis.2015610e1913e191310.1038/cddis.2015.26426469962
     [Google Scholar]
  21. HearnB.R. JaishankarP. SidrauskiC. TsaiJ.C. VedanthamP. FontaineS.D. WalterP. RensloA.R. Structure–activity studies of Bis- O -Arylglycolamides: Inhibitors of the integrated stress response.ChemMedChem201611887088010.1002/cmdc.20150048326789650
     [Google Scholar]
  22. HosoiT. KakimotoM. TanakaK. NomuraJ. OzawaK. Unique pharmacological property of ISRIB in inhibition of Aβ-induced neuronal cell death.J. Pharmacol. Sci.2016131429229510.1016/j.jphs.2016.08.00327569458
     [Google Scholar]
  23. BriggsJ.A. LiV.C. LeeS. WoolfC.J. KleinA. KirschnerM.W. Mouse embryonic stem cells can differentiate via multiple paths to the same state.eLife20176e2694510.7554/eLife.2694528990928
     [Google Scholar]
  24. WongY.L. LeBonL. BassoA.M. KohlhaasK.L. NikkelA.L. RobbH.M. Donnelly-RobertsD.L. PrakashJ. SwensenA.M. RubinsteinN.D. KrishnanS. McAllisterF.E. HasteN.V. O’BrienJ.J. RoyM. IrelandA. FrostJ.M. ShiL. RiedmaierS. MartinK. DartM.J. SidrauskiC. eIF2B activator prevents neurological defects caused by a chronic integrated stress response.eLife20198e4294010.7554/eLife.4294030624206
     [Google Scholar]
  25. WongY.L. LeBonL. EdaljiR. LimH.B. SunC. SidrauskiC. The small molecule ISRIB rescues the stability and activity of Vanishing White Matter Disease eIF2B mutant complexes.eLife20187e3273310.7554/eLife.3273329489452
     [Google Scholar]
  26. ZhuP.J. KhatiwadaS. CuiY. ReinekeL.C. DoolingS.W. KimJ.J. LiW. WalterP. Costa-MattioliM. Activation of the ISR mediates the behavioral and neurophysiological abnormalities in Down syndrome.Science2019366646784384910.1126/science.aaw518531727829
     [Google Scholar]
  27. RabouwH.H. LangereisM.A. AnandA.A. VisserL.J. de GrootR.J. WalterP. van KuppeveldF.J.M. Small molecule ISRIB suppresses the integrated stress response within a defined window of activation.Proc. Natl. Acad. Sci. USA201911662097210210.1073/pnas.181576711630674674
     [Google Scholar]
  28. AbbinkT.E.M. WisseL.E. JakuE. ThieckeM.J. Voltolini-GonzálezD. FritsenH. BobeldijkS. ter BraakT.J. PolderE. PostmaN.L. BugianiM. StruijsE.A. VerheijenM. StraatN. van der SluisS. ThomasA.A.M. MolenaarD. van der KnaapM.S. Vanishing white matter: Deregulated integrated stress response as therapy target.Ann. Clin. Transl. Neurol.2019681407142210.1002/acn3.5082631402619
     [Google Scholar]
  29. Barragán-IglesiasP. KuhnJ. Vidal-CantúG.C. Salinas-AbarcaA.B. Granados-SotoV. DussorG.O. CampbellZ.T. PriceT.J. Activation of the integrated stress response in nociceptors drives methylglyoxal-induced pain.Pain2019160116017110.1097/j.pain.000000000000138730157134
     [Google Scholar]
  30. Young-BairdS.K. LourençoM.B. ElderM.K. KlannE. LiebauS. DeverT.E. Suppression of MEHMO syndrome mutation in eIF2 by small molecule ISRIB.Mol. Cell2020774875886.e710.1016/j.molcel.2019.11.00831836389
     [Google Scholar]
  31. JewerM. LeeL. LeibovitchM. ZhangG. LiuJ. FindlayS.D. VincentK.M. TandocK. Dieters-CastatorD. QuailD.F. DuttaI. CoathamM. XuZ. PuriA. GuanB.J. HatzoglouM. BrumwellA. UniackeJ. PatsisC. KoromilasA. SchuelerJ. SiegersG.M. TopisirovicI. PostovitL.M. Translational control of breast cancer plasticity.Nat. Commun.2020111249810.1038/s41467‑020‑16352‑z32427827
     [Google Scholar]
  32. MahameedM. BoukeilehS. ObiedatA. DarawshiO. DiptaP. RimonA. McLennanG. FasslerR. ReichmannD. KarniR. PreisingerC. WilhelmT. HuberM. TiroshB. Pharmacological induction of selective endoplasmic reticulum retention as a strategy for cancer therapy.Nat. Commun.2020111130410.1038/s41467‑020‑15067‑532161259
     [Google Scholar]
  33. RashidiA. MiskaJ. Lee-ChangC. KanojiaD. PanekW.K. Lopez-RosasA. ZhangP. HanY. XiaoT. PituchK.C. KimJ.W. GCN2 is essential for CD8+ T cell survival and function in murine models of malignant glioma.Cancer Immunol Immunother.20206918194
     [Google Scholar]
  34. WilliamsM.S. AmaralF.M.R. SimeoniF. SomervailleT.C.P. A stress-responsive enhancer induces dynamic drug resistance in acute myeloid leukemia.J. Clin. Invest.202013031217123210.1172/JCI13080931770110
     [Google Scholar]
  35. SchoofM. BooneM. WangL. LawrenceR. FrostA. WalterP. eIF2B conformation and assembly state regulate the integrated stress response.eLife202110e6570310.7554/eLife.6570333688831
     [Google Scholar]
  36. BugalloR. MarlinE. BaltanásA. ToledoE. FerreroR. Vinueza-GavilanesR. LarreaL. ArrasateM. AragónT. Fine tuning of the unfolded protein response by ISRIB improves neuronal survival in a model of amyotrophic lateral sclerosis.Cell Death Dis.202011539710.1038/s41419‑020‑2601‑232457286
     [Google Scholar]
  37. ZhangD. McGregorM. DeckerM.W. QuikM. The α7 nicotinic receptor agonist ABT-107 decreases L-Dopa-induced dyskinesias in parkinsonian monkeys.J. Pharmacol. Exp. Ther.20143511253210.1124/jpet.114.21628325034405
     [Google Scholar]
  38. LorenzN.I. SittigA.C.M. UrbanH. LugerA.L. EngelA.L. MünchC. SteinbachJ.P. RonellenfitschM.W. Activating transcription factor 4 mediates adaptation of human glioblastoma cells to hypoxia and temozolomide.Sci. Rep.20211111416110.1038/s41598‑021‑93663‑134239013
     [Google Scholar]
  39. BhattacharyaB. XiaoS. ChatterjeeS. UrbanowskiM. OrdonezA. IhmsE.A. AgrahariG. LunS. BerlandR. PichuginA. GaoY. ConnorJ. IvanovA.R. YanB.S. KobzikL. KooB.B. JainS. BishaiW. KramnikI. The integrated stress response mediates necrosis in murine Mycobacterium tuberculosis granulomas.J. Clin. Invest.20211313e13031910.1172/JCI13031933301427
     [Google Scholar]
  40. LlácerJ.L. HussainT. MarlerL. AitkenC.E. ThakurA. LorschJ.R. HinnebuschA.G. RamakrishnanV. Conformational differences between open and closed states of the eukaryotic translation initiation complex.Mol. Cell201559339941210.1016/j.molcel.2015.06.03326212456
     [Google Scholar]
  41. KashiwagiK. YokoyamaT. NishimotoM. TakahashiM. SakamotoA. YonemochiM. ShirouzuM. ItoT. Structural basis for eIF2B inhibition in integrated stress response.Science2019364643949549910.1126/science.aaw410431048492
     [Google Scholar]
  42. AdomaviciusT. GuaitaM. ZhouY. JenningsM.D. LatifZ. RosemanA.M. PavittG.D. The structural basis of translational control by eIF2 phosphorylation.Nat. Commun.2019101213610.1038/s41467‑019‑10167‑331086188
     [Google Scholar]
  43. GordiyenkoY. LlácerJ.L. RamakrishnanV. Structural basis for the inhibition of translation through eIF2α phosphorylation.Nat. Commun.2019101264010.1038/s41467‑019‑10606‑130602773
     [Google Scholar]
  44. ZyryanovaA.F. KashiwagiK. RatoC. HardingH.P. Crespillo-CasadoA. PereraL.A. SakamotoA. NishimotoM. YonemochiM. ShirouzuM. ItoT. RonD. ISRIB blunts the integrated stress response by allosterically antagonising the inhibitory effect of phosphorylated eIF2 on eIF2B.Mol. Cell202181188103.e610.1016/j.molcel.2020.10.03133220178
     [Google Scholar]
  45. HenselerI. RegenbrechtF. ObrigH. Lesion correlates of patholinguistic profiles in chronic aphasia: Comparisons of syndrome-, modality- and symptom-level assessment.Brain2014137391893010.1093/brain/awt37424525451
     [Google Scholar]
  46. DamasioA.R. Aphasia.N. Engl. J. Med.1992326853153910.1056/NEJM1992022032608061732792
     [Google Scholar]
  47. American Speech-Language-Hearing AssociationMaking effective communication, a human right, accessible and achievable for all.2024Available From: www.asha.org
  48. AnandA.A. WalterP. Structural insights into ISRIB, a memory-enhancing inhibitor of the integrated stress response.FEBS J.2020287223924510.1111/febs.1507331550413
     [Google Scholar]
  49. ChouA. KrukowskiK. JopsonT. ZhuP.J. Costa-MattioliM. WalterP. RosiS. Inhibition of the integrated stress response reverses cognitive deficits after traumatic brain injury.Proc. Natl. Acad. Sci. USA201711431E6420E642610.1073/pnas.170766111428696288
     [Google Scholar]
  50. LiJ. AkilO. RouseS.L. McLaughlinC.W. MatthewsI.R. LustigL.R. ChanD.K. SherrE.H. Deletion of Tmtc4 activates the unfolded protein response and causes postnatal hearing loss.J. Clin. Invest.2018128115150516210.1172/JCI9749830188326
     [Google Scholar]
  51. RouseS.L. MatthewsI.R. LiJ. SherrE.H. ChanD.K. Integrated stress response inhibition provides sex-dependent protection against noise-induced cochlear synaptopathy.Sci. Rep.20201011806310.1038/s41598‑020‑75058‑w33093490
     [Google Scholar]
  52. NguyenH.G. ConnC.S. KyeY. XueL. ForesterC.M. CowanJ.E. HsiehA.C. CunninghamJ.T. TruilletC. TameireF. EvansM.J. EvansC.P. YangJ.C. HannB. KoumenisC. WalterP. CarrollP.R. RuggeroD. Development of a stress response therapy targeting aggressive prostate cancer.Sci. Transl. Med.201810439eaar203610.1126/scitranslmed.aar203629720449
     [Google Scholar]
  53. Saura-EstellerJ. Sánchez-VeraI. Núñez-VázquezS. CosiallsA.M. Gama-PérezP. BhosaleG. Mendive-TapiaL. LavillaR. PonsG. Garcia-RovesP.M. DuchenM.R. Iglesias-SerretD. GilJ. Activation of the Integrated Stress Response and ER Stress Protect from Fluorizoline-Induced Apoptosis in HEK293T and U2OS Cell Lines.Int. J. Mol. Sci.20212211611710.3390/ijms2211611734204139
     [Google Scholar]
  54. MarlinE. Viu-IdocinC. ArrasateM. AragónT. The role and therapeutic potential of the integrated stress response in amyotrophic lateral sclerosis.Int. J. Mol. Sci.20222314782310.3390/ijms2314782335887167
     [Google Scholar]
  55. SidhomE. O’BrienJ.T. ButcherA.J. SmithH.L. MallucciG.R. UnderwoodB.R. Targeting the unfolded protein response as a disease-modifying pathway in dementia.Int. J. Mol. Sci.2022234202110.3390/ijms2304202135216136
     [Google Scholar]
  56. WatanabeS. MarkovN.S. LuZ. Piseaux AillonR. SoberanesS. RunyanC.E. RenZ. GrantR.A. MacielM. Abdala-ValenciaH. PolitanskaY. NamK. SichizyaL. KihshenH.G. JoshiN. McQuattie-PimentelA.C. GrunerK.A. JainM. SznajderJ.I. MorimotoR.I. ReyfmanP.A. GottardiC.J. BudingerG.R.S. MisharinA.V. Resetting proteostasis with ISRIB promotes epithelial differentiation to attenuate pulmonary fibrosis.Proc. Natl. Acad. Sci. USA202111820e210110011810.1073/pnas.210110011833972447
     [Google Scholar]
  57. DudkaW. HoserG. MondalS.S. Turos-KorgulL. SwatlerJ. Kusio-KobiałkaM. WolczykM. KlejmanA. Brewinska-OlchowikM. KominekA. WiechM. Targeting Integrated Stress Response by ISRIB combined with imatinib attenuates STAT5 signaling and eradicates therapy-resistant Chronic Myeloid Leukemia cells.bioRxiv202120210510.1101/2021.05.05.442756
     [Google Scholar]
  58. HuangT. LuoL. JiangS. ChenC. HeH. LiangC. LiW. WangH. ZhuL. WangK. GuoY. Targeting integrated stress response regulates microglial M1/M2 polarization and attenuates neuroinflammation following surgical brain injury in rat.Cell. Signal.20218511004810.1016/j.cellsig.2021.11004834015470
     [Google Scholar]
  59. WangC. TanZ. NiuB. TsangK.Y. TaiA. ChanW.C.W. LoR.L.K. LeungK.K.H. DungN.W.F. ItohN. ZhangM.Q. ChanD. CheahK.S.E. Inhibiting the integrated stress response pathway prevents aberrant chondrocyte differentiation thereby alleviating chondrodysplasia.eLife20187e3767310.7554/eLife.3767330024379
     [Google Scholar]
  60. JohnsonE.C.B. KangJ. A small molecule targeting protein translation does not rescue spatial learning and memory deficits in the hAPP-J20 mouse model of Alzheimer’s disease.PeerJ20164e256510.7717/peerj.256527781164
     [Google Scholar]
  61. FangF. LiuP. HuangH. FengX. LiL. SunY. KaufmanR.J. HuY. RGC-specific ATF4 and/or CHOP deletion rescues glaucomatous neurodegeneration and visual function.Mol. Ther. Nucleic Acids20233328629510.1016/j.omtn.2023.07.01537547290
     [Google Scholar]
  62. ChiariniL.B. Petrs-SilvaH. LindenR. Novel approaches to glaucomatous neurodegeneration, based on the integrated stress response.Mol. Ther. Nucleic Acids20233384584710.1016/j.omtn.2023.08.02237662966
     [Google Scholar]
  63. TongF. HuH. XuY. ZhouY. XieR. LeiT. DuY. YangW. HeS. HuangY. GongT. GaoH. Hollow copper sulfide nanoparticles carrying ISRIB for the sensitized photothermal therapy of breast cancer and brain metastases through inhibiting stress granule formation and reprogramming tumor-associated macrophages.Acta Pharm. Sin. B20231383471348810.1016/j.apsb.2022.11.00337655313
     [Google Scholar]
  64. XuS. GierischM.E. BarchiE. PoserI. AlbertiS. SalomonsF.A. DantumaN.P. Chemical inhibition of the integrated stress response impairs the ubiquitin-proteasome system.bioRxiv202410.1101/2024.03.13.584747
     [Google Scholar]
  65. YanG. HanZ. KwonY. JousmaJ. NukalaS.B. ProsserB.L. DuX. PinhoS. OngS.B. LeeW.H. OngS.G. Integrated stress response potentiates ponatinib-induced cardiotoxicity.Circ Res.2024134548250110.1161/CIRCRESAHA.123.323683
     [Google Scholar]
  66. RyuS. WeberC. ChuP.H. ErnestB. JovanovicV.M. DengT. SlameckaJ. HongH. JethmalaniY. BaskirH.M. InmanJ. BraistedJ. HirstM.B. SimeonovA. VossT.C. TristanC.A. SingeçI. Stress-free cell aggregation by using the CEPT cocktail enhances embryoid body and organoid fitness.Biofabrication202416101501610.1088/1758‑5090/ad0d1337972398
     [Google Scholar]
  67. ChenG. DongZ. Targeting a single codon to rescue septic acute kidney injury.J. Am. Soc. Nephrol.202334217918110.1681/ASN.000000000000002136735369
     [Google Scholar]
  68. GoswamiP. AkhterJ. ManglaA. SuramyaS. JindalG. AhmadS. RaisuddinS. Downregulation of ATF-4 attenuates the endoplasmic reticulum stress–mediated neuroinflammation and cognitive impairment in experimentally induced alzheimer’s disease model.Mol. Neurobiol.20236185071508210.1007/s12035‑023‑03861‑338159199
     [Google Scholar]
  69. LuH. KojuN. ShengR. Mammalian integrated stress responses in stressed organelles and their functions.Acta Pharmacol. Sin.202412010.1038/s41401‑023‑01225‑038267546
     [Google Scholar]
  70. KutschkaI. BerteroE. WasmusC. XiaoK. YangL. ChenX. OshimaY. FischerM. ErkM. ArslanB. AlhasanL. GrosserD. ErmerK.J. NickelA. KohlhaasM. EberlH. RebsS. Streckfuss-BömekeK. SchmitzW. RehlingP. ThumT. HiguchiT. RabinowitzJ. MaackC. DudekJ. Activation of the integrated stress response rewires cardiac metabolism in Barth syndrome.Basic Res. Cardiol.202311814710.1007/s00395‑023‑01017‑x37930434
     [Google Scholar]
  71. HuiS.U.N. HongfuJ.I.N. ShenruiG.U.O. YiyuanF.E.N.G. YafuY.I.N. HuiW.A.N.G. WeiweiC.H.E.N.G. Research progress of integrated stress response in pathogenesis of Alzheimer’s disease.J. Shanghai Jiaotong Univ.2023436755
     [Google Scholar]
  72. HuR. ChenX. SuQ. WangZ. WangX. GongM. XuM. LeR. GaoY. DaiP. ZhangZ.N. ShaoL. LiW. ISR inhibition reverses pancreatic β-cell failure in Wolfram syndrome models.Cell Death Differ.202431332233410.1038/s41418‑024‑01258‑w38321214
     [Google Scholar]
  73. PerninF. CuiQ.L. MohammadniaA. FernandesM.G.F. HallJ.A. SrourM. DudleyR.W.R. ZandeeS.E.J. KlementW. PratA. SalapaH.E. LevinM.C. MooreG.R.W. KennedyT.E. Vande VeldeC. AntelJ.P. Regulation of stress granule formation in human oligodendrocytes.Nat. Commun.2024151152410.1038/s41467‑024‑45746‑638374028
     [Google Scholar]
  74. PeiY. LiuS. WangL. ChenC. HuM. XueY. GuanD. XieL. LiaoH. ZhouJ. ZhangH. Design, synthesis, and biological evaluation of eukaryotic initiation factor 2B (eIF2B) activators.ChemMedChem2024e20230071610.1002/cmdc.20230071638426720
     [Google Scholar]
  75. YuX. DangL. ZhangR. YangW. Therapeutic potential of targeting the PERK signaling pathway in ischemic stroke.Pharmaceuticals (Basel)202417335310.3390/ph1703035338543139
     [Google Scholar]
  76. WalterP. SidrauskiC. AlvearD.A. ArkinM.R. WilsonC.G. AngK.H. HearnB.R. VedanthamP. RensloA.R. MazeM. VacasS. Modulators of the eif2alpha pathway.US Patent 9708247B22017
  77. GarthE. Calico licenses memory-enhancing drug ISRIB.2019Available From: https://longevity.technology/news/calico-licenses-memory-enhancing-drug-isrib/
  78. PubMedAvailable From: pubmed.ncbi.nlm.nih.gov
  79. ClinicalTrials.gov ClinicalTrials.gov is a place to learn about clinical studies from around the world.2023Available From: https://clinicaltrials.gov/
  80. Fight AgingTowards clinical trials for ISRIB.2022Available From: www.fightaging.org/archives/ 2022/ 01/towards-clinical-trials-for-isrib/
    [Google Scholar]
  81. MlynarykN. Small-molecule drug reverses neural effects of concussion: UCSF researchers rescue cognitive function by blocking molecular stress response with ISRIB.2022Available From: www.ucsf.edu/news/2022/10/423981/ small-molecule-drug-reverses-neural-effects-concussion
  82. Alzforumtherapeutics DNL343.2023Available From: www.alzforum.org/therapeutics/dnl343
  83. CalicoCalico Life Sciences in collaboration with AbbVie.2023Available From: www.massgeneral.org/assets /mgh/pdf/neurology/als/regimenf_calicosabbv-cls-7262drugsciencewebinar_2023.pdf
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Maximizing ISRIB Potential Requires Addressing Specificity, Long-term Safety, and Disease-specific Considerations
Curr. Med. Chem. 32, 2482 (2025); https://doi.org/10.2174/0109298673290924240514061916
/content/journals/cmc/10.2174/0109298673290924240514061916
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  • Article Type:     Review Article
Keyword(s): Alzheimer’s disease; clinical trials; cognitive disorders; Drugs; ISRIB; Parkinson's disease

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