Target Information

Target General Infomation
Target ID
T81735
Former ID
TTDR01142
Target Name
DNA-dependent protein kinase catalytic subunit
Gene Name
PRKDC
Synonyms
DNA-PK; DNA-PKcs; DNA-dependent protein kinase; DNPK1; P460; PRKDC
Target Type
Research
Disease Cancer [ICD9: 140-229; ICD10: C00-C96]
Prostate cancer [ICD9: 185; ICD10: C61]
Function
Ser/thr kinase involved in dna double-stranded break repair, v(d)j recombination and modulation of transcription. Must be bound to dna to express its catalytic properties.
BioChemical Class
Kinase
Target Validation
T81735
UniProt ID
P78527
EC Number
EC 2.7.11.1
Sequence
MAGSGAGVRCSLLRLQETLSAADRCGAALAGHQLIRGLGQECVLSSSPAVLALQTSLVFS
RDFGLLVFVRKSLNSIEFRECREEILKFLCIFLEKMGQKIAPYSVEIKNTCTSVYTKDRA
AKCKIPALDLLIKLLQTFRSSRLMDEFKIGELFSKFYGELALKKKIPDTVLEKVYELLGL
LGEVHPSEMINNAENLFRAFLGELKTQMTSAVREPKLPVLAGCLKGLSSLLCNFTKSMEE
DPQTSREIFNFVLKAIRPQIDLKRYAVPSAGLRLFALHASQFSTCLLDNYVSLFEVLLKW
CAHTNVELKKAALSALESFLKQVSNMVAKNAEMHKNKLQYFMEQFYGIIRNVDSNNKELS
IAIRGYGLFAGPCKVINAKDVDFMYVELIQRCKQMFLTQTDTGDDRVYQMPSFLQSVASV
LLYLDTVPEVYTPVLEHLVVMQIDSFPQYSPKMQLVCCRAIVKVFLALAAKGPVLRNCIS
TVVHQGLIRICSKPVVLPKGPESESEDHRASGEVRTGKWKVPTYKDYVDLFRHLLSSDQM
MDSILADEAFFSVNSSSESLNHLLYDEFVKSVLKIVEKLDLTLEIQTVGEQENGDEAPGV
WMIPTSDPAANLHPAKPKDFSAFINLVEFCREILPEKQAEFFEPWVYSFSYELILQSTRL
PLISGFYKLLSITVRNAKKIKYFEGVSPKSLKHSPEDPEKYSCFALFVKFGKEVAVKMKQ
YKDELLASCLTFLLSLPHNIIELDVRAYVPALQMAFKLGLSYTPLAEVGLNALEEWSIYI
DRHVMQPYYKDILPCLDGYLKTSALSDETKNNWEVSALSRAAQKGFNKVVLKHLKKTKNL
SSNEAISLEEIRIRVVQMLGSLGGQINKNLLTVTSSDEMMKSYVAWDREKRLSFAVPFRE
MKPVIFLDVFLPRVTELALTASDRQTKVAACELLHSMVMFMLGKATQMPEGGQGAPPMYQ
LYKRTFPVLLRLACDVDQVTRQLYEPLVMQLIHWFTNNKKFESQDTVALLEAILDGIVDP
VDSTLRDFCGRCIREFLKWSIKQITPQQQEKSPVNTKSLFKRLYSLALHPNAFKRLGASL
AFNNIYREFREEESLVEQFVFEALVIYMESLALAHADEKSLGTIQQCCDAIDHLCRIIEK
KHVSLNKAKKRRLPRGFPPSASLCLLDLVKWLLAHCGRPQTECRHKSIELFYKFVPLLPG
NRSPNLWLKDVLKEEGVSFLINTFEGGGCGQPSGILAQPTLLYLRGPFSLQATLCWLDLL
LAALECYNTFIGERTVGALQVLGTEAQSSLLKAVAFFLESIAMHDIIAAEKCFGTGAAGN
RTSPQEGERYNYSKCTVVVRIMEFTTTLLNTSPEGWKLLKKDLCNTHLMRVLVQTLCEPA
SIGFNIGDVQVMAHLPDVCVNLMKALKMSPYKDILETHLREKITAQSIEELCAVNLYGPD
AQVDRSRLAAVVSACKQLHRAGLLHNILPSQSTDLHHSVGTELLSLVYKGIAPGDERQCL
PSLDLSCKQLASGLLELAFAFGGLCERLVSLLLNPAVLSTASLGSSQGSVIHFSHGEYFY
SLFSETINTELLKNLDLAVLELMQSSVDNTKMVSAVLNGMLDQSFRERANQKHQGLKLAT
TILQHWKKCDSWWAKDSPLETKMAVLALLAKILQIDSSVSFNTSHGSFPEVFTTYISLLA
DTKLDLHLKGQAVTLLPFFTSLTGGSLEELRRVLEQLIVAHFPMQSREFPPGTPRFNNYV
DCMKKFLDALELSQSPMLLELMTEVLCREQQHVMEELFQSSFRRIARRGSCVTQVGLLES
VYEMFRKDDPRLSFTRQSFVDRSLLTLLWHCSLDALREFFSTIVVDAIDVLKSRFTKLNE
STFDTQITKKMGYYKILDVMYSRLPKDDVHAKESKINQVFHGSCITEGNELTKTLIKLCY
DAFTENMAGENQLLERRRLYHCAAYNCAISVICCVFNELKFYQGFLFSEKPEKNLLIFEN
LIDLKRRYNFPVEVEVPMERKKKYIEIRKEAREAANGDSDGPSYMSSLSYLADSTLSEEM
SQFDFSTGVQSYSYSSQDPRPATGRFRRREQRDPTVHDDVLELEMDELNRHECMAPLTAL
VKHMHRSLGPPQGEEDSVPRDLPSWMKFLHGKLGNPIVPLNIRLFLAKLVINTEEVFRPY
AKHWLSPLLQLAASENNGGEGIHYMVVEIVATILSWTGLATPTGVPKDEVLANRLLNFLM
KHVFHPKRAVFRHNLEIIKTLVECWKDCLSIPYRLIFEKFSGKDPNSKDNSVGIQLLGIV
MANDLPPYDPQCGIQSSEYFQALVNNMSFVRYKEVYAAAAEVLGLILRYVMERKNILEES
LCELVAKQLKQHQNTMEDKFIVCLNKVTKSFPPLADRFMNAVFFLLPKFHGVLKTLCLEV
VLCRVEGMTELYFQLKSKDFVQVMRHRDDERQKVCLDIIYKMMPKLKPVELRELLNPVVE
FVSHPSTTCREQMYNILMWIHDNYRDPESETDNDSQEIFKLAKDVLIQGLIDENPGLQLI
IRNFWSHETRLPSNTLDRLLALNSLYSPKIEVHFLSLATNFLLEMTSMSPDYPNPMFEHP
LSECEFQEYTIDSDWRFRSTVLTPMFVETQASQGTLQTRTQEGSLSARWPVAGQIRATQQ
QHDFTLTQTADGRSSFDWLTGSSTDPLVDHTSPSSDSLLFAHKRSERLQRAPLKSVGPDF
GKKRLGLPGDEVDNKVKGAAGRTDLLRLRRRFMRDQEKLSLMYARKGVAEQKREKEIKSE
LKMKQDAQVVLYRSYRHGDLPDIQIKHSSLITPLQAVAQRDPIIAKQLFSSLFSGILKEM
DKFKTLSEKNNITQKLLQDFNRFLNTTFSFFPPFVSCIQDISCQHAALLSLDPAAVSAGC
LASLQQPVGIRLLEEALLRLLPAELPAKRVRGKARLPPDVLRWVELAKLYRSIGEYDVLR
GIFTSEIGTKQITQSALLAEARSDYSEAAKQYDEALNKQDWVDGEPTEAEKDFWELASLD
CYNHLAEWKSLEYCSTASIDSENPPDLNKIWSEPFYQETYLPYMIRSKLKLLLQGEADQS
LLTFIDKAMHGELQKAILELHYSQELSLLYLLQDDVDRAKYYIQNGIQSFMQNYSSIDVL
LHQSRLTKLQSVQALTEIQEFISFISKQGNLSSQVPLKRLLNTWTNRYPDAKMDPMNIWD
DIITNRCFFLSKIEEKLTPLPEDNSMNVDQDGDPSDRMEVQEQEEDISSLIRSCKFSMKM
KMIDSARKQNNFSLAMKLLKELHKESKTRDDWLVSWVQSYCRLSHCRSRSQGCSEQVLTV
LKTVSLLDENNVSSYLSKNILAFRDQNILLGTTYRIIANALSSEPACLAEIEEDKARRIL
ELSGSSSEDSEKVIAGLYQRAFQHLSEAVQAAEEEAQPPSWSCGPAAGVIDAYMTLADFC
DQQLRKEEENASVIDSAELQAYPALVVEKMLKALKLNSNEARLKFPRLLQIIERYPEETL
SLMTKEISSVPCWQFISWISHMVALLDKDQAVAVQHSVEEITDNYPQAIVYPFIISSESY
SFKDTSTGHKNKEFVARIKSKLDQGGVIQDFINALDQLSNPELLFKDWSNDVRAELAKTP
VNKKNIEKMYERMYAALGDPKAPGLGAFRRKFIQTFGKEFDKHFGKGGSKLLRMKLSDFN
DITNMLLLKMNKDSKPPGNLKECSPWMSDFKVEFLRNELEIPGQYDGRGKPLPEYHVRIA
GFDERVTVMASLRRPKRIIIRGHDEREHPFLVKGGEDLRQDQRVEQLFQVMNGILAQDSA
CSQRALQLRTYSVVPMTSRLGLIEWLENTVTLKDLLLNTMSQEEKAAYLSDPRAPPCEYK
DWLTKMSGKHDVGAYMLMYKGANRTETVTSFRKRESKVPADLLKRAFVRMSTSPEAFLAL
RSHFASSHALICISHWILGIGDRHLNNFMVAMETGGVIGIDFGHAFGSATQFLPVPELMP
FRLTRQFINLMLPMKETGLMYSIMVHALRAFRSDPGLLTNTMDVFVKEPSFDWKNFEQKM
LKKGGSWIQEINVAEKNWYPRQKICYAKRKLAGANPAVITCDELLLGHEKAPAFRDYVAV
ARGSKDHNIRAQEPESGLSEETQVKCLMDQATDPNILGRTWEGWEPWM
Inhibitor 1-Morpholin-4-yl-benzo[f]chromen-3-one Drug Info [527386]
2-(1H-indol-5-yl)-6-morpholino-4H-pyran-4-one Drug Info [528738]
2-(2-aminophenyl)-6-morpholino-4H-pyran-4-one Drug Info [528738]
2-(2-Fluoro-phenyl)-benzo[h]chromen-4-one Drug Info [527386]
2-(2-methoxyphenyl)-6-morpholino-4H-pyran-4-one Drug Info [528738]
2-(2-Methyl-morpholin-4-yl)-benzo[h]chromen-4-one Drug Info [527296]
2-(3-acetylphenyl)-6-morpholino-4H-pyran-4-one Drug Info [528738]
2-(3-Fluoro-phenyl)-benzo[h]chromen-4-one Drug Info [527386]
2-(3-methoxyphenyl)-6-morpholino-4H-pyran-4-one Drug Info [528738]
2-(4-Amino-phenyl)-benzo[h]chromen-4-one Drug Info [527386]
2-(4-chlorophenyl)-6-morpholino-4H-pyran-4-one Drug Info [528738]
2-(4-fluorophenyl)-6-morpholino-4H-pyran-4-one Drug Info [528738]
2-(4-methoxyphenyl)-6-morpholino-4H-pyran-4-one Drug Info [528738]
2-(benzofuran-2-yl)-6-morpholino-4H-pyran-4-one Drug Info [528738]
2-(furan-2-yl)-6-morpholino-4H-pyran-4-one Drug Info [528738]
2-(piperidin-1-yl)-4H-benzo[h]chromen-4-one Drug Info [527888]
2-biphenyl-4-yl-6-morpholin-4-yl-pyran-4-one Drug Info [528738]
2-dibenzofuran-4-yl-6-morpholin-4-yl-pyran-4-one Drug Info [528738]
2-morpholin-4-yl-6-phenyl-4H-thiopyran-4-one Drug Info [528738]
2-Morpholin-4-yl-6-phenyl-chromen-4-one Drug Info [527386]
2-morpholin-4-yl-8-naphthalen-2-ylchromen-4-one Drug Info [527888]
2-morpholin-4-yl-8-phenoxathiin-4-ylchromen-4-one Drug Info [527888]
2-morpholin-4-yl-8-styrylchromen-4-one Drug Info [527888]
2-morpholin-4-yl-8-thiophen-2-ylchromen-4-one Drug Info [527888]
2-morpholin-4-yl-8-thiophen-3-ylchromen-4-one Drug Info [527888]
2-Morpholin-4-yl-benzo[h]chromene-4-thione Drug Info [527386]
2-Morpholin-4-yl-pyrido[1,2-a]pyrimidin-4-one Drug Info [527386]
2-Morpholin-4-yl-pyrimido[2,1-a]isoquinolin-4-one Drug Info [527386]
2-morpholino-4H-benzo[g]chromen-4-one Drug Info [527888]
2-morpholino-6-(naphthalen-1-yl)-4H-chromen-4-one Drug Info [527888]
2-morpholino-6-(naphthalen-1-yl)-4H-pyran-4-one Drug Info [528738]
2-morpholino-6-(naphthalen-2-yl)-4H-pyran-4-one Drug Info [528738]
2-morpholino-6-(quinolin-8-yl)-4H-pyran-4-one Drug Info [528738]
2-morpholino-6-(thianthren-1-yl)-4H-chromen-4-one Drug Info [527888]
2-morpholino-6-(thiophen-2-yl)-4H-pyran-4-one Drug Info [528738]
2-morpholino-6-(thiophen-3-yl)-4H-pyran-4-one Drug Info [528738]
2-morpholino-6-phenyl-4H-pyran-4-one Drug Info [528738]
2-morpholino-6-styryl-4H-pyran-4-one Drug Info [528738]
2-morpholinobenzo[h]quinolin-4(1H)-one Drug Info [527888]
2-Pyridin-3-yl-benzo[h]chromen-4-one Drug Info [527386]
2-Pyrrolidin-1-yl-benzo[h]chromen-4-one Drug Info [527386]
2-Thiomorpholin-4-yl-pyrido[1,2-a]pyrimidin-4-one Drug Info [527386]
2-thiomorpholino-4H-benzo[h]chromen-4-one Drug Info [527888]
2-[1,4]Oxazepan-4-yl-benzo[h]chromen-4-one Drug Info [527386]
3-(6-morpholino-4-oxo-4H-pyran-2-yl)benzaldehyde Drug Info [528738]
3-(6-morpholino-4-oxo-4H-pyran-2-yl)benzoic acid Drug Info [528738]
3-(6-morpholino-4-oxo-4H-pyran-2-yl)benzonitrile Drug Info [528738]
3-morpholino-1H-benzo[f]chromen-1-one Drug Info [528738]
4-(6-morpholino-4-oxo-4H-pyran-2-yl)benzonitrile Drug Info [528738]
4-Morpholin-4-yl-benzo[g]chromen-2-one Drug Info [527386]
4-Morpholin-4-yl-benzo[h]chromen-2-one Drug Info [527386]
4-Morpholin-4-yl-chromen-2-one Drug Info [527386]
4-morpholino-6-phenyl-2H-pyran-2-one Drug Info [528738]
4-Piperidin-1-yl-chromen-2-one Drug Info [527386]
4-Thiomorpholin-4-yl-benzo[g]chromen-2-one Drug Info [527386]
6-(2-acetylphenyl)-2-morpholin-4-ylchromen-4-one Drug Info [527888]
6-(3-hydroxyphenyl)-2-morpholino-4H-chromen-4-one Drug Info [527888]
6-(4-chlorophenyl)-2-morpholin-4-ylpyridin-4-ol Drug Info [528738]
6-(4-chlorophenyl)-4-morpholino-2H-pyran-2-one Drug Info [528738]
6-(4-fluorostyryl)-2-morpholino-4H-chromen-4-one Drug Info [527888]
6-(4-hydroxyphenyl)-2-morpholino-4H-chromen-4-one Drug Info [527888]
6-(4-methoxyphenyl)-4-morpholino-2H-pyran-2-one Drug Info [528738]
6-biphenyl-2-yl-2-morpholin-4-yl-chromen-4-one Drug Info [527888]
6-Chloro-4-morpholin-4-yl-chromen-2-one Drug Info [527386]
6-isopropyl-2-morpholin-4-yl-4H-thiopyran-4-one Drug Info [528738]
6-Methoxy-4-morpholin-4-yl-chromen-2-one Drug Info [527386]
6-Methyl-4-morpholin-4-yl-chromen-2-one Drug Info [527386]
6-tert-Butyl-2-morpholin-4-yl-4H-thiopyran-4-one Drug Info [528738]
7-benzoyloxy-2-(morpholin-4-yl)-chromen-4-one Drug Info [527888]
7-benzyloxy-2-(morpholin-4-yl)-chromen-4-one Drug Info [527888]
7-ethyloxyethoxy-2-morpholin-4-yl-chromen-4-one Drug Info [527888]
7-hydroxy-2-(morpholin-4-yl)chromen-4-one Drug Info [527888]
7-Methoxy-2-morpholin-4-yl-chromen-4-one Drug Info [527386]
7-Methoxy-4-morpholin-4-yl-chromen-2-one Drug Info [527386]
7-phenylethoxy-2-morpholin-4-yl-chromen-4-one Drug Info [527888]
7-phenyloxyethoxy-2-morpholin-4-yl-chromen-4-one Drug Info [527888]
7-propoxy-2-(morpholin-4-yl)-chromen-4-one Drug Info [527888]
8-(1H-indol-5-yl)-2-morpholin-4-ylchromen-4-one Drug Info [527888]
8-(2-acetylphenyl)-2-morpholin-4-ylchromen-4-one Drug Info [527888]
8-(3-hydroxyphenyl)-2-morpholin-4-ylchromen-4-one Drug Info [527888]
8-(4-acetylphenyl)-2-morpholin-4-ylchromen-4-one Drug Info [527888]
8-(4-chlorophenyl)-2-morpholin-4-ylchromen-4-one Drug Info [527888]
8-(4-hydroxyphenyl)-2-morpholin-4-ylchromen-4-one Drug Info [527888]
8-biphenyl-2-yl-2-morpholin-4-ylchromen-4-one Drug Info [527888]
8-dibenzofuran-4-yl-2-morpholin-4-ylchromen-4-one Drug Info [527888]
8-furan-2-yl-2-morpholin-4-ylchromen-4-one Drug Info [527888]
8-Methoxy-2-morpholin-4-yl-chromen-4-one Drug Info [527386]
8-Methoxy-4-morpholin-4-yl-chromen-2-one Drug Info [527386]
8-Methyl-2-morpholin-4-yl-chromen-4-one Drug Info [527386]
8-Methyl-4-morpholin-4-yl-chromen-2-one Drug Info [527386]
8-Phenyl-2-piperidin-1-yl-chromen-4-one Drug Info [527386]
8-Phenyl-2-thiomorpholin-4-yl-chromen-4-one Drug Info [527386]
ALPHA-NAPHTHOFLAVONE Drug Info [527386]
AMA37 Drug Info [528888]
IC86621 Drug Info [531979]
KU-0060648 Drug Info [532428]
KU-55933 Drug Info [528738]
LY-292223 Drug Info [527296]
LY-293646 Drug Info [527888]
NU-7432 Drug Info [527888]
PIK-75 Drug Info [528169]
PP121 Drug Info [529744]
Pathways
KEGG Pathway Non-homologous end-joining
Cell cycle
NetPath Pathway IL1 Signaling Pathway
Pathway Interaction Database DNA-PK pathway in nonhomologous end joining
Coregulation of Androgen receptor activity
Class I PI3K signaling events mediated by Akt
BARD1 signaling events
Reactome Nonhomologous End-Joining (NHEJ)
WikiPathways DNA Damage Response
Non-homologous end joining
FAS pathway and Stress induction of HSP regulation
Cytosolic sensors of pathogen-associated DNA
Retinoblastoma (RB) in Cancer
Prostate Cancer
Double-Strand Break Repair
Cell Cycle
miRNA Regulation of DNA Damage Response
References
Ref 527296Bioorg Med Chem Lett. 2004 Dec 20;14(24):6083-7.Identification of a highly potent and selective DNA-dependent protein kinase (DNA-PK) inhibitor (NU7441) by screening of chromenone libraries.
Ref 527386J Med Chem. 2005 Jan 27;48(2):569-85.Selective benzopyranone and pyrimido[2,1-a]isoquinolin-4-one inhibitors of DNA-dependent protein kinase: synthesis, structure-activity studies, and radiosensitization of a human tumor cell line in vitro.
Ref 527888J Med Chem. 2005 Dec 1;48(24):7829-46.Discovery of potent chromen-4-one inhibitors of the DNA-dependent protein kinase (DNA-PK) using a small-molecule library approach.
Ref 528169A pharmacological map of the PI3-K family defines a role for p110alpha in insulin signaling. Cell. 2006 May 19;125(4):733-47. Epub 2006 Apr 27.
Ref 528738J Med Chem. 2007 Apr 19;50(8):1958-72. Epub 2007 Mar 20.Pyranone, thiopyranone, and pyridone inhibitors of phosphatidylinositol 3-kinase related kinases. Structure-activity relationships for DNA-dependent protein kinase inhibition, and identification of the first potent and selective inhibitor of the ataxia telangiectasia mutated kinase.
Ref 528888Inhibition of mammalian target of rapamycin signaling by 2-(morpholin-1-yl)pyrimido[2,1-alpha]isoquinolin-4-one. J Biol Chem. 2007 Aug 17;282(33):24463-70. Epub 2007 Jun 11.
Ref 529744Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases. Nat Chem Biol. 2008 Nov;4(11):691-9.
Ref 531979Modulation of DNA repair by pharmacological inhibitors of the PIKK protein kinase family. Bioorg Med Chem Lett. 2012 Sep 1;22(17):5352-9.
Ref 5324281-substituted (Dibenzo[b,d]thiophen-4-yl)-2-morpholino-4H-chromen-4-ones endowed with dual DNA-PK/PI3-K inhibitory activity. J Med Chem. 2013 Aug 22;56(16):6386-401.
Ref 543716(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2800).
Ref 1587926URL: https://www.ebi.ac.uk/chembl/ The ChEMBL database in 2017

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