GSK2606414

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WARNING: This product is for research use only, not for human or veterinary use.

Description:GSK2606414 is an orally available, potent, and selective PERK inhibitor. GSK2606414 inhibits PERK activation in cells and inhibits the growth of a human tumor xenograft in mice. Protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) is activated in response to a variety of endoplasmic reticulum stresses implicated in numerous disease states. Evidence that PERK is implicated in tumorigenesis and cancer cell survival stimulated our search for small molecule inhibitors.

Price and Availability

GSK2606414, purity > 98%, is in stock. The same day shipping after order is received.

Chemical Structure

Theoretical Analysis

MedKoo Cat#: 406393Name: GSK2606414CAS#: 1337531-36-8Chemical Formula: C24H20F3N5OExact Mass: 451.16199Molecular Weight: 451.44Elemental Analysis: C, 63.85; H, 4.47; F, 12.63; N, 15.51; O, 3.54

Synonym:GSK2606414; GSK-2606414; GSK 2606414; GSK PERK Inhibitor.

IUPAC/Chemical Name:1-(5-(4-amino-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)indolin-1-yl)-2-(3-(trifluoromethyl)phenyl)ethanone

InChi Key:SIXVRXARNAVBTC-UHFFFAOYSA-N

InChi Code:InChI=1S/C24H20F3N5O/c1-31-12-18(21-22(28)29-13-30-23(21)31)15-5-6-19-16(11-15)7-8-32(19)20(33)10-14-3-2-4-17(9-14)24(25,26)27/h2-6,9,11-13H,7-8,10H2,1H3,(H2,28,29,30)

SMILES Code:FC(C1=CC(CC(N2CCC3=C2C=CC(C4=CN(C)C5=NC=NC(N)=C54)=C3)=O)=CC=C1)(F)F

Technical Data

Additional Information

    The chemical structures of GSK2606414  and GSK2656157 are very similar. The following graphic is a side-by-side comparison.  

References

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2: Wen L, Xiao B, Shi Y, Han F. PERK signalling pathway mediates single prolonged stress-induced dysfunction of medial prefrontal cortex neurons. Apoptosis. 2017 Jun;22(6):753-768. doi: 10.1007/s10495-017-1371-5. PubMed PMID: 28391375.

3: Jiang X, Wei Y, Zhang T, Zhang Z, Qiu S, Zhou X, Zhang S. Effects of GSK2606414 on cell proliferation and endoplasmic reticulum stress associated gene expression in retinal pigment epithelial cells. Mol Med Rep. 2017 May;15(5):3105-3110. doi: 10.3892/mmr.2017.6418. Epub 2017 Mar 30. PubMed PMID: 28358434.

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6: Abhishek K, Sardar AH, Das S, Kumar A, Ghosh AK, Singh R, Saini S, Mandal A, Verma S, Kumar A, Purkait B, Dikhit MR, Das P. Phosphorylation of Translation Initiation Factor 2-Alpha in Leishmania donovani under Stress Is Necessary for Parasite Survival. Mol Cell Biol. 2016 Dec 19;37(1). pii: e00344-16. Print 2017 Jan 1. PubMed PMID: 27736773; PubMed Central PMCID: PMC5192082.

7: Wu WS, Chien CC, Chen YC, Chiu WT. Protein Kinase RNA-Like Endoplasmic Reticulum Kinase-Mediated Bcl-2 Protein Phosphorylation Contributes to Evodiamine-Induced Apoptosis of Human Renal Cell Carcinoma Cells. PLoS One. 2016Aug 2;11(8):e0160484. doi: 10.1371/journal.pone.0160484. eCollection 2016. PubMed PMID: 27483435; PubMed Central PMCID: PMC4970736.

8: Celardo I, Costa AC, Lehmann S, Jones C, Wood N, Mencacci NE, Mallucci GR, Loh SH, Martins LM. Mitofusin-mediated ER stress triggers neurodegeneration in pink1/parkin models of Parkinson"s disease. Cell Death Dis. 2016 Jun 23;7(6):e2271. doi: 10.1038/cddis.2016.173. PubMed PMID: 27336715; PubMed Central PMCID: PMC5143399.

9: Guthrie LN, Abiraman K, Plyler ES, Sprenkle NT, Gibson SA, McFarland BC, Rajbhandari R, Rowse AL, Benveniste EN, Meares GP. Attenuation of PKR-like ER Kinase (PERK) Signaling Selectively Controls Endoplasmic Reticulum Stress-induced Inflammation Without Compromising Immunological Responses. J Biol Chem. 2016 Jul22;291(30):15830-40. doi: 10.1074/jbc.M116.738021. Epub 2016 May 23. PubMed PMID: 27226638; PubMed Central PMCID: PMC4957064.

10: Zhou Y, Qi B, Gu Y, Xu F, Du H, Li X, Fang W. Porcine Circovirus 2 Deploys PERK Pathway and GRP78 for Its Enhanced Replication in PK-15 Cells. Viruses. 2016 Feb 20;8(2). pii: E56. doi: 10.3390/v8020056. PubMed PMID: 26907328; PubMed Central PMCID: PMC4776210.

11: Chen TC, Chien CC, Wu MS, Chen YC. Evodiamine from Evodia rutaecarpa inducesapoptosis via activation of JNK and PERK in human ovarian cancer cells. Phytomedicine. 2016 Jan 15;23(1):68-78. doi: 10.1016/j.phymed.2015.12.003. Epub 2015 Dec 22. PubMed PMID: 26902409.

12: Yan F, Cao S, Li J, Dixon B, Yu X, Chen J, Gu C, Lin W, Chen G. Pharmacological Inhibition of PERK Attenuates Early Brain Injury After Subarachnoid Hemorrhage in Rats Through the Activation of Akt. Mol Neurobiol. 2017 Apr;54(3):1808-1817. doi: 10.1007/s12035-016-9790-9. Epub 2016 Feb 18. PubMed PMID: 26887383.

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14: Johari YB, Estes SD, Alves CS, Sinacore MS, James DC. Integrated cell and process engineering for improved transient production of a "difficult-to-express" fusion protein by CHO cells. Biotechnol Bioeng. 2015 Dec;112(12):2527-42. doi: 10.1002/bit.25687. Epub 2015 Sep 7. PubMed PMID: 26126657.

15: Jamison S, Lin Y, Lin W. Pancreatic endoplasmic reticulum kinase activation promotes medulloblastoma cell migration and invasion through induction of vascular endothelial growth factor A. PLoS One. 2015 Mar 20;10(3):e0120252. doi:10.1371/journal.pone.0120252. eCollection 2015. PubMed PMID: 25794107; PubMed Central PMCID: PMC4368580.

16: Halliday M, Radford H, Sekine Y, Moreno J, Verity N, le Quesne J, Ortori CA,Barrett DA, Fromont C, Fischer PM, Harding HP, Ron D, Mallucci GR. Partial restoration of protein synthesis rates by the small molecule ISRIB prevents neurodegeneration without pancreatic toxicity. Cell Death Dis. 2015 Mar 5;6:e1672. doi: 10.1038/cddis.2015.49. PubMed PMID: 25741597; PubMed Central PMCID: PMC4385927.

17: Moon HS, Kim B, Gwak H, Suh DH, Song YS. Autophagy and protein kinase RNA-like endoplasmic reticulum kinase (PERK)/eukaryotic initiation factor 2 alpha kinase (eIF2α) pathway protect ovarian cancer cells from metformin-induced apoptosis. Mol Carcinog. 2016 Apr;55(4):346-56. doi: 10.1002/mc.22284. Epub 2015Feb 7. PubMed PMID: 25663310.

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19: Ounallah-Saad H, Sharma V, Edry E, Rosenblum K. Genetic or pharmacological reduction of PERK enhances cortical-dependent taste learning. J Neurosci. 2014 Oct 29;34(44):14624-32. doi: 10.1523/JNEUROSCI.2117-14.2014. PubMed PMID: 25355215.

20: Axten JM, Romeril SP, Shu A, Ralph J, Medina JR, Feng Y, Li WH, Grant SW, Heerding DA, Minthorn E, Mencken T, Gaul N, Goetz A, Stanley T, Hassell AM, Gampe RT, Atkins C, Kumar R. Discovery of GSK2656157: An Optimized PERK Inhibitor Selected for Preclinical Development. ACS Med Chem Lett. 2013 Aug 12;4(10):964-8. doi: 10.1021/ml400228e. eCollection 2013 Oct 10. PubMed PMID: 24900593; PubMed Central PMCID: PMC4027568.