General Information of the Protein
Protein ID
PT02815
Protein Name
Eukaryotic translation initiation factor 2-alpha kinase 3
Secondarily
Protein Name
PRKR-like endoplasmic reticulum kinase
Pancreatic eIF2-alpha kinase
Gene Name
EIF2AK3
Secondarily
Gene Name
PEK
PERK
Sequence
MERAISPGLLVRALLLLLLLLGLAARTVAAGRARGLPAPTAEAAFGLGAAAAPTSATRVPAAGAVAAAEVTVEDAEALPAAAGEQEPRGPEPDDETELRPRGRSLVIISTLDGRIAALDPENHGKKQWDLDVGSGSLVSSSLSKPEVFGNKMIIPSLDGALFQWDQDRESMETVPFTVESLLESSYKFGDDVVLVGGKSLTTYGLSAYSGKVRYICSALGCRQWDSDEMEQEEDILLLQRTQKTVRAVGPRSGNEKWNFSVGHFELRYIPDMETRAGFIESTFKPNENTEESKIISDVEEQEAAIMDIVIKVSVADWKVMAFSKKGGHLEWEYQFCTPIASAWLLKDGKVIPISLFDDTSYTSNDDVLEDEEDIVEAARGATENSVYLGMYRGQLYLQSSVRISEKFPSSPKALESVTNENAIIPLPTIKWKPLIHSPSRTPVLVGSDEFDKCLSNDKFSHEEYSNGALSILQYPYDNGYYLPYYKRERNKRSTQITVRFLDNPHYNKNIRKKDPVLLLHWWKEIVATILFCIIATTFIVRRLFHPHPHRQRKESETQCQTENKYDSVSGEANDSSWNDIKNSGYISRYLTDFEPIQCLGRGGFGVVFEAKNKVDDCNYAIKRIRLPNRELAREKVMREVKALAKLEHPGIVRYFNAWLEAPPEKWQEKMDEIWLKDESTDWPLSSPSPMDAPSVKIRRMDPFATKEHIEIIAPSPQRSRSFSVGISCDQTSSSESQFSPLEFSGMDHEDISESVDAAYNLQDSCLTDCDVEDGTMDGNDEGHSFELCPSEASPYVRSRERTSSSIVFEDSGCDNASSKEEPKTNRLHIGNHCANKLTAFKPTSSKSSSEATLSISPPRPTTLSLDLTKNTTEKLQPSSPKVYLYIQMQLCRKENLKDWMNGRCTIEERERSVCLHIFLQIAEAVEFLHSKGLMHRDLKPSNIFFTMDDVVKVGDFGLVTAMDQDEEEQTVLTPMPAYARHTGQVGTKLYMSPEQIHGNSYSHKVDIFSLGLILFELLYPFSTQMERVRTLTDVRNLKFPPLFTQKYPCEYVMVQDMLSPSPMERPEAINIIENAVFEDLDFPGKTVLRQRSRSLSSSGTKHSRQSNNSHSPLPSN
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Organism
Homo sapiens, Human
Protein Classification
Enzyme
>
Kinase
>
Protein Kinase
>
Other protein kinase group
>
Other protein kinase PEK family
>
Other protein kinase PEK subfamily
Function
Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) in response to various stress conditions. Key activator of the integrated stress response (ISR) required for adaptation to various stress, such as unfolded protein response (UPR) and low amino acid availability (By similarity). EIF2S1/eIF-2-alpha phosphorylation in response to stress converts EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, leading to a global attenuation of cap-dependent translation, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activators ATF4 and QRICH1, and hence allowing ATF4- and QRICH1-mediated reprogramming (PubMed:33384352). Serves as a critical effector of unfolded protein response (UPR)-induced G1 growth arrest due to the loss of cyclin-D1 (CCND1). Involved in control of mitochondrial morphology and function (By similarity).
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Uniprot ID
Primary ID:
Q9NZJ5

Secondarily ID:
A0AVH1
A0AVH2
B2RCU9
O95846
Q53QY0
Q53SB1
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Ensembl ID
ENSG00000172071
HGNC ID
HGNC:3255
Subcellular Location
Endoplasmic reticulum membrane
Map of Molecular Bioactivity Related to the Protein
Map of Molecular Bioactivity Related to the Protein

Protein
Cell Line
Compound

Bioactivity Value:

<= 0.1 μM
> 0.1 μM and <= 10 μM
> 10 μM
Imprecise Activity
Table of Molecular Bioactivities Related to the Protein
Cell Line ID: CL000068 , A-549
Compound ID Compound Name Compound Formula
CP0073258
1-[5-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)-2,3-dihydroindol-1-yl]-2-[3-(trifluoromethyl)phenyl]ethanone
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C24H20F3N5O
 1
1
IC50 < 30 nM
   TI
   LI
   LO
   TS
CP0077833
1-[5-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)-2,3-dihydroindol-1-yl]-2-(2,3,5-trifluorophenyl)ethanone
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C23H18F3N5O
 1
1
IC50 = 30 nM
   TI
   LI
   LO
   TS
CP0077837
1-[5-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)-2,3-dihydroindol-1-yl]-2-(2,5-difluorophenyl)ethanone
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C23H19F2N5O
 1
1
IC50 = 30 nM
   TI
   LI
   LO
   TS
CP0247867
1-[5-[4-amino-7-(1-methylpyrazol-4-yl)thieno[3,2-c]pyridin-3-yl]-2,3-dihydroindol-1-yl]-2-phenylethanone
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C27H23N5OS
 1
1
IC50 = 30 nM
   TI
   LI
   LO
   TS
CP0279338
1-[5-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)-2,3-dihydroindol-1-yl]-2-(3-chlorophenyl)ethanone
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C23H20ClN5O
 1
1
IC50 < 30 nM
   TI
   LI
   LO
   TS
CP0066296
1-[5-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)-4-fluoro-2,3-dihydroindol-1-yl]-2-(3,5-dimethylpyrazol-1-yl)ethanone
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C22H22FN7O
 1
1
IC50 = 30 nM
   TI
   LI
   LO
   TS
CP0144021
1-[5-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)-4-fluoro-2,3-dihydroindol-1-yl]-2-[6-(trifluoromethyl)pyridin-2-yl]ethanone
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C23H18F4N6O
 1
1
IC50 < 30 nM
   TI
   LI
   LO
   TS
CP0144025
1-[5-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)-4-fluoro-2,3-dihydroindol-1-yl]-2-(6-methylpyridin-2-yl)ethanone
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C23H21FN6O
 1
1
IC50 = 30 nM
   TI
   LI
   LO
   TS
CP0266638
1-[5-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)-2,3-dihydroindol-1-yl]-2-[6-(trifluoromethyl)pyridin-2-yl]ethanone
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C23H19F3N6O
 1
1
IC50 = 30 nM
   TI
   LI
   LO
   TS
CP0282643
1-[5-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)-2,3-dihydroindol-1-yl]-2-(4-fluorophenyl)ethanone
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C23H20FN5O
 1
1
IC50 = 100 nM
   TI
   LI
   LO
   TS
CP0303744
1-[5-(4-amino-7-pyridin-3-ylthieno[3,2-c]pyridin-3-yl)-2,3-dihydroindol-1-yl]-2-phenylethanone
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C28H22N4OS
 1
1
IC50 = 100 nM
   TI
   LI
   LO
   TS
CP0368347
1-[5-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)-2,3-dihydroindol-1-yl]-2-(3,5-dimethylpyrazol-1-yl)ethanone
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C22H23N7O
 1
1
IC50 = 100 nM
   TI
   LI
   LO
   TS
CP0369471
1-[5-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)-2,3-dihydroindol-1-yl]-2-(6-methylpyridin-2-yl)ethanone
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C23H22N6O
 1
1
IC50 = 100 nM
   TI
   LI
   LO
   TS
CP0279337
1-[5-(4-aminothieno[3,2-c]pyridin-3-yl)-2,3-dihydroindol-1-yl]-2-phenylethanone
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C23H19N3OS
 1
1
IC50 > 300 nM
   TI
   LI
   LO
   TS
Biochemical Assays
Compound ID Compound Name Compound Formula
CP0077833
1-[5-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)-2,3-dihydroindol-1-yl]-2-(2,3,5-trifluorophenyl)ethanone
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C23H18F3N5O
 1
1 IC50 = 0.2 nM
CP0279338
1-[5-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)-2,3-dihydroindol-1-yl]-2-(3-chlorophenyl)ethanone
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C23H20ClN5O
 1
1 IC50 = 0.2 nM
CP0555049
2-(2,5-difluorophenyl)-1-[5-[(6,7-dimethoxyquinazolin-4-yl)amino]-2,3-dihydroindol-1-yl]ethanone
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C26H22F2N4O3
 1
1 IC50 = 0.3981 nM
CP0073258
1-[5-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)-2,3-dihydroindol-1-yl]-2-[3-(trifluoromethyl)phenyl]ethanone
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C24H20F3N5O
 1
1 IC50 = 0.4 nM
CP0077837
1-[5-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)-2,3-dihydroindol-1-yl]-2-(2,5-difluorophenyl)ethanone
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C23H19F2N5O
 1
1 IC50 = 0.4 nM
CP0144021
1-[5-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)-4-fluoro-2,3-dihydroindol-1-yl]-2-[6-(trifluoromethyl)pyridin-2-yl]ethanone
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C23H18F4N6O
 1
1 IC50 = 0.5 nM
CP0266638
1-[5-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)-2,3-dihydroindol-1-yl]-2-[6-(trifluoromethyl)pyridin-2-yl]ethanone
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C23H19F3N6O
 1
1 IC50 = 0.5 nM
CP0474367
1-[5-[(6,7-dimethoxyquinazolin-4-yl)amino]-2,3-dihydroindol-1-yl]-2-(6-fluoro-2-methyl-1H-indol-3-yl)ethanone
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C29H26FN5O3
 1
1 IC50 = 0.631 nM
CP0537557
1-[5-[(6,7-dimethoxyquinazolin-4-yl)amino]-2,3-dihydroindol-1-yl]-2-(2-methyl-1H-indol-3-yl)ethanone
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C29H27N5O3
 1
1 IC50 = 0.7943 nM
CP0144025
1-[5-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)-4-fluoro-2,3-dihydroindol-1-yl]-2-(6-methylpyridin-2-yl)ethanone
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C23H21FN6O
 1
1 IC50 = 0.8 nM
CP0247164
1-[5-[(6,7-dimethoxyquinazolin-4-yl)amino]-4-fluoro-2,3-dihydroindol-1-yl]-2-(2-methyl-1H-indol-3-yl)ethanone
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C29H26FN5O3
 1
1 IC50 = 1 nM
CP0247867
1-[5-[4-amino-7-(1-methylpyrazol-4-yl)thieno[3,2-c]pyridin-3-yl]-2,3-dihydroindol-1-yl]-2-phenylethanone
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C27H23N5OS
 1
1 IC50 = 1.3 nM
CP0282643
1-[5-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)-2,3-dihydroindol-1-yl]-2-(4-fluorophenyl)ethanone
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C23H20FN5O
 1
1 IC50 = 1.5 nM
CP0508306
1-[5-[(6,7-dimethoxyquinazolin-4-yl)amino]-2,3-dihydroindol-1-yl]-2-(7-fluoro-2-methyl-1H-indol-3-yl)ethanone
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C29H26FN5O3
 1
1 IC50 = 1.585 nM
CP0368347
1-[5-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)-2,3-dihydroindol-1-yl]-2-(3,5-dimethylpyrazol-1-yl)ethanone
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C22H23N7O
 1
1 IC50 = 1.9 nM
CP0369471
1-[5-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)-2,3-dihydroindol-1-yl]-2-(6-methylpyridin-2-yl)ethanone
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C23H22N6O
 1
1 IC50 = 2.5 nM
CP0066296
1-[5-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)-4-fluoro-2,3-dihydroindol-1-yl]-2-(3,5-dimethylpyrazol-1-yl)ethanone
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C22H22FN7O
 1
1 IC50 = 2.7 nM
CP0555752
1-[5-[(6,7-dimethoxyquinazolin-4-yl)amino]-2,3-dihydroindol-1-yl]-2-(6-fluoro-2-methylindol-1-yl)ethanone
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C29H26FN5O3
 1
1 IC50 = 3.162 nM
CP0303744
1-[5-(4-amino-7-pyridin-3-ylthieno[3,2-c]pyridin-3-yl)-2,3-dihydroindol-1-yl]-2-phenylethanone
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C28H22N4OS
 1
1 IC50 = 3.2 nM
CP0303258
1-[5-[(6,7-dimethoxyquinazolin-4-yl)amino]-2,3-dihydroindol-1-yl]-2-(1H-indol-3-yl)ethanone
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C28H25N5O3
 1
1 IC50 = 5.012 nM
CP0553571
1-[5-[(6,7-dimethoxyquinazolin-4-yl)amino]-2,3-dihydroindol-1-yl]-2-indol-1-ylethanone
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C28H25N5O3
 1
1 IC50 = 6.31 nM
CP0174802
2-(1-benzofuran-3-yl)-1-[5-[(6,7-dimethoxyquinazolin-4-yl)amino]-2,3-dihydroindol-1-yl]ethanone
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C28H24N4O4
 1
1 IC50 = 10 nM
CP0279337
1-[5-(4-aminothieno[3,2-c]pyridin-3-yl)-2,3-dihydroindol-1-yl]-2-phenylethanone
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C23H19N3OS
 1
1 IC50 = 11.7 nM
CP0426670
1-[5-[(6,7-dimethoxyquinazolin-4-yl)amino]-2,3-dihydroindol-1-yl]-2-(1-methylpyrazol-3-yl)ethanone
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C24H24N6O3
 1
1 IC50 = 251.19 nM
Clinical Information about the Protein
Target 1 ( PRKR-like endoplasmic reticulum kinase (PERK) )
Target Type Clinical trial Target
Target 2 ( Pancreatic eIF2-alpha kinase (HsPEK) )
Target Type Literature-reported Target