Target Information

Target General Information

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Target ID

T81735 (Former ID: TTDR01142)

Target Name

DNA-dependent protein kinase catalytic (PRKDC)

Synonyms

p460; HYRC1; HYRC; DNPK1; DNA-dependent protein kinase catalytic subunit; DNA-PKcs; DNA-PK catalytic subunit

Gene Name

PRKDC

Target Type

Clinical trial target

[1]

Disease

[+] 2 Target-related Diseases

Rectum cancer [ICD-11: 2B92]

Solid tumour/cancer [ICD-11: 2A00-2F9Z]

Function

Serine/threonine-protein kinase that acts as a molecular sensor for DNA damage. Involved in DNA non-homologous end joining (NHEJ) required for double-strand break (DSB) repair and V(D)J recombination. Must be bound to DNA to express its catalytic properties. Promotes processing of hairpin DNA structures in V(D)J recombination by activation of the hairpin endonuclease artemis (DCLRE1C). The assembly of the DNA-PK complex at DNA ends is also required for the NHEJ ligation step. Required to protect and align broken ends of DNA. May also act as a scaffold protein to aid the localization of DNA repair proteins to the site of damage. Found at the ends of chromosomes, suggesting a further role in the maintenance of telomeric stability and the prevention of chromosomal end fusion. Also involved in modulation of transcription. Recognizes the substrate consensus sequence [ST]-Q. Phosphorylates 'Ser-139' of histone variant H2AX/H2AFX, thereby regulating DNA damage response mechanism. Phosphorylates DCLRE1C, c-Abl/ABL1, histone H1, HSPCA, c-jun/JUN, p53/TP53, PARP1, POU2F1, DHX9, FH, SRF, XRCC1, XRCC1, XRCC4, XRCC5, XRCC6, WRN, MYC and RFA2. Can phosphorylate C1D not only in the presence of linear DNA but also in the presence of supercoiled DNA. Ability to phosphorylate p53/TP53 in the presence of supercoiled DNA is dependent on C1D. Contributes to the determination of the circadian period length by antagonizing phosphorylation of CRY1 'Ser-588' and increasing CRY1 protein stability, most likely through an indirect mechanism (By similarity). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway.

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BioChemical Class

Kinase

UniProt ID

PRKDC_HUMAN

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

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3D Structure

Click to Show 3D Structure of This Target

PDB

HIT2.0 ID

T98QOA

Drugs and Modes of Action

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Clinical Trial Drug(s)

[+] 3 Clinical Trial Drugs

AZD7648

Drug Info

Phase 1/2

Solid tumour/cancer

[2]

M3814

Drug Info

Phase 1/2

Locally advanced rectal cancer

[3]

M9831

Drug Info

Phase 1

Solid tumour/cancer

[1]

Mode of Action

[+] 1 Modes of Action

Inhibitor

[+] 105 Inhibitor drugs

AZD7648

Drug Info

[4]

M3814

Drug Info

[1]

M9831

Drug Info

[1]

1-Morpholin-4-yl-benzo[f]chromen-3-one

Drug Info

[5]

2-(1H-indol-5-yl)-6-morpholino-4H-pyran-4-one

Drug Info

[6]

2-(2-aminophenyl)-6-morpholino-4H-pyran-4-one

Drug Info

[6]

2-(2-Fluoro-phenyl)-benzo[h]chromen-4-one

Drug Info

[5]

2-(2-methoxyphenyl)-6-morpholino-4H-pyran-4-one

Drug Info

[6]

2-(2-Methyl-morpholin-4-yl)-benzo[h]chromen-4-one

Drug Info

[7]

2-(3-acetylphenyl)-6-morpholino-4H-pyran-4-one

Drug Info

[6]

2-(3-Fluoro-phenyl)-benzo[h]chromen-4-one

Drug Info

[5]

2-(3-methoxyphenyl)-6-morpholino-4H-pyran-4-one

Drug Info

[6]

2-(4-Amino-phenyl)-benzo[h]chromen-4-one

Drug Info

[5]

2-(4-chlorophenyl)-6-morpholino-4H-pyran-4-one

Drug Info

[6]

2-(4-fluorophenyl)-6-morpholino-4H-pyran-4-one

Drug Info

[6]

2-(4-methoxyphenyl)-6-morpholino-4H-pyran-4-one

Drug Info

[6]

2-(benzofuran-2-yl)-6-morpholino-4H-pyran-4-one

Drug Info

[6]

2-(furan-2-yl)-6-morpholino-4H-pyran-4-one

Drug Info

[6]

2-(piperidin-1-yl)-4H-benzo[h]chromen-4-one

Drug Info

[8]

2-biphenyl-4-yl-6-morpholin-4-yl-pyran-4-one

Drug Info

[6]

2-dibenzofuran-4-yl-6-morpholin-4-yl-pyran-4-one

Drug Info

[6]

2-morpholin-4-yl-6-phenyl-4H-thiopyran-4-one

Drug Info

[6]

2-Morpholin-4-yl-6-phenyl-chromen-4-one

Drug Info

[5]

2-morpholin-4-yl-8-naphthalen-2-ylchromen-4-one

Drug Info

[8]

2-morpholin-4-yl-8-phenoxathiin-4-ylchromen-4-one

Drug Info

[8]

2-morpholin-4-yl-8-styrylchromen-4-one

Drug Info

[8]

2-morpholin-4-yl-8-thiophen-2-ylchromen-4-one

Drug Info

[8]

2-morpholin-4-yl-8-thiophen-3-ylchromen-4-one

Drug Info

[8]

2-Morpholin-4-yl-benzo[h]chromene-4-thione

Drug Info

[5]

2-Morpholin-4-yl-pyrido[1,2-a]pyrimidin-4-one

Drug Info

[5]

2-Morpholin-4-yl-pyrimido[2,1-a]isoquinolin-4-one

Drug Info

[5]

2-morpholino-4H-benzo[g]chromen-4-one

Drug Info

[8]

2-morpholino-6-(naphthalen-1-yl)-4H-chromen-4-one

Drug Info

[8]

2-morpholino-6-(naphthalen-1-yl)-4H-pyran-4-one

Drug Info

[6]

2-morpholino-6-(naphthalen-2-yl)-4H-pyran-4-one

Drug Info

[6]

2-morpholino-6-(quinolin-8-yl)-4H-pyran-4-one

Drug Info

[6]

2-morpholino-6-(thianthren-1-yl)-4H-chromen-4-one

Drug Info

[8]

2-morpholino-6-(thiophen-2-yl)-4H-pyran-4-one

Drug Info

[6]

2-morpholino-6-(thiophen-3-yl)-4H-pyran-4-one

Drug Info

[6]

2-morpholino-6-phenyl-4H-pyran-4-one

Drug Info

[6]

2-morpholino-6-styryl-4H-pyran-4-one

Drug Info

[6]

2-morpholinobenzo[h]quinolin-4(1H)-one

Drug Info

[8]

2-Pyridin-3-yl-benzo[h]chromen-4-one

Drug Info

[5]

2-Pyrrolidin-1-yl-benzo[h]chromen-4-one

Drug Info

[5]

2-Thiomorpholin-4-yl-pyrido[1,2-a]pyrimidin-4-one

Drug Info

[5]

2-thiomorpholino-4H-benzo[h]chromen-4-one

Drug Info

[8]

2-[1,4]Oxazepan-4-yl-benzo[h]chromen-4-one

Drug Info

[5]

3-(6-morpholino-4-oxo-4H-pyran-2-yl)benzaldehyde

Drug Info

[6]

3-(6-morpholino-4-oxo-4H-pyran-2-yl)benzoic acid

Drug Info

[6]

3-(6-morpholino-4-oxo-4H-pyran-2-yl)benzonitrile

Drug Info

[6]

3-morpholino-1H-benzo[f]chromen-1-one

Drug Info

[6]

4-(6-morpholino-4-oxo-4H-pyran-2-yl)benzonitrile

Drug Info

[6]

4-Morpholin-4-yl-benzo[g]chromen-2-one

Drug Info

[5]

4-Morpholin-4-yl-benzo[h]chromen-2-one

Drug Info

[5]

4-Morpholin-4-yl-chromen-2-one

Drug Info

[5]

4-morpholino-6-phenyl-2H-pyran-2-one

Drug Info

[6]

4-Piperidin-1-yl-chromen-2-one

Drug Info

[5]

4-Thiomorpholin-4-yl-benzo[g]chromen-2-one

Drug Info

[5]

6-(2-acetylphenyl)-2-morpholin-4-ylchromen-4-one

Drug Info

[8]

6-(3-hydroxyphenyl)-2-morpholino-4H-chromen-4-one

Drug Info

[8]

6-(4-chlorophenyl)-2-morpholin-4-ylpyridin-4-ol

Drug Info

[6]

6-(4-chlorophenyl)-4-morpholino-2H-pyran-2-one

Drug Info

[6]

6-(4-fluorostyryl)-2-morpholino-4H-chromen-4-one

Drug Info

[8]

6-(4-hydroxyphenyl)-2-morpholino-4H-chromen-4-one

Drug Info

[8]

6-(4-methoxyphenyl)-4-morpholino-2H-pyran-2-one

Drug Info

[6]

6-biphenyl-2-yl-2-morpholin-4-yl-chromen-4-one

Drug Info

[8]

6-Chloro-4-morpholin-4-yl-chromen-2-one

Drug Info

[5]

6-isopropyl-2-morpholin-4-yl-4H-thiopyran-4-one

Drug Info

[6]

6-Methoxy-4-morpholin-4-yl-chromen-2-one

Drug Info

[5]

6-Methyl-4-morpholin-4-yl-chromen-2-one

Drug Info

[5]

6-tert-Butyl-2-morpholin-4-yl-4H-thiopyran-4-one

Drug Info

[6]

7-benzoyloxy-2-(morpholin-4-yl)-chromen-4-one

Drug Info

[8]

7-benzyloxy-2-(morpholin-4-yl)-chromen-4-one

Drug Info

[8]

7-ethyloxyethoxy-2-morpholin-4-yl-chromen-4-one

Drug Info

[8]

7-hydroxy-2-(morpholin-4-yl)chromen-4-one

Drug Info

[8]

7-Methoxy-2-morpholin-4-yl-chromen-4-one

Drug Info

[5]

7-Methoxy-4-morpholin-4-yl-chromen-2-one

Drug Info

[5]

7-phenylethoxy-2-morpholin-4-yl-chromen-4-one

Drug Info

[8]

7-phenyloxyethoxy-2-morpholin-4-yl-chromen-4-one

Drug Info

[8]

7-propoxy-2-(morpholin-4-yl)-chromen-4-one

Drug Info

[8]

8-(1H-indol-5-yl)-2-morpholin-4-ylchromen-4-one

Drug Info

[8]

8-(2-acetylphenyl)-2-morpholin-4-ylchromen-4-one

Drug Info

[8]

8-(3-hydroxyphenyl)-2-morpholin-4-ylchromen-4-one

Drug Info

[8]

8-(4-acetylphenyl)-2-morpholin-4-ylchromen-4-one

Drug Info

[8]

8-(4-chlorophenyl)-2-morpholin-4-ylchromen-4-one

Drug Info

[8]

8-(4-hydroxyphenyl)-2-morpholin-4-ylchromen-4-one

Drug Info

[8]

8-biphenyl-2-yl-2-morpholin-4-ylchromen-4-one

Drug Info

[8]

8-dibenzofuran-4-yl-2-morpholin-4-ylchromen-4-one

Drug Info

[8]

8-furan-2-yl-2-morpholin-4-ylchromen-4-one

Drug Info

[8]

8-Methoxy-2-morpholin-4-yl-chromen-4-one

Drug Info

[5]

8-Methoxy-4-morpholin-4-yl-chromen-2-one

Drug Info

[5]

8-Methyl-2-morpholin-4-yl-chromen-4-one

Drug Info

[5]

8-Methyl-4-morpholin-4-yl-chromen-2-one

Drug Info

[5]

8-Phenyl-2-piperidin-1-yl-chromen-4-one

Drug Info

[5]

8-Phenyl-2-thiomorpholin-4-yl-chromen-4-one

Drug Info

[5]

ALPHA-NAPHTHOFLAVONE

Drug Info

[5]

AMA37

Drug Info

[9]

Ethyl 1-[(1H-benzimidazol-2(3H)one-5-yl)sulfonyl]-1H-pyrrole-2-carboxylate

Drug Info

[8]

IC86621

Drug Info

[10]

100

KU-0060648

Drug Info

[11]

101

KU-55933

Drug Info

[6]

102

LY-292223

Drug Info

[7]

103

NU-7432

Drug Info

[8]

104

PIK-75

Drug Info

[12]

105

PP121

Drug Info

[13]

Chemical Structure based Activity Landscape of Target

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Drug Property Profile of Target

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(1) Molecular Weight (mw) based Drug Clustering

(2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering

(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering

(4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering

(5) Rotatable Bond Count (rotbonds) based Drug Clustering

(6) Topological Polar Surface Area (polararea) based Drug Clustering

"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five

Target Poor or Non Binders

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Target Poor or Non Binders

Target Poor or Non Binders Info

Target Regulators

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Target-regulating microRNAs

Target-regulating microRNAs Info

Target-interacting Proteins

Target-interacting Proteins Info

Target Affiliated Biological Pathways

Top

KEGG Pathway

[+] 2 KEGG Pathways

Non-homologous end-joining

Cell cycle

NetPath Pathway

[+] 1 NetPath Pathways

IL1 Signaling Pathway

PID Pathway

[+] 4 PID Pathways

DNA-PK pathway in nonhomologous end joining

Coregulation of Androgen receptor activity

Class I PI3K signaling events mediated by Akt

BARD1 signaling events

Reactome

[+] 1 Reactome Pathways

Nonhomologous End-Joining (NHEJ)

WikiPathways

[+] 9 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

Target-Related Models and Studies

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Target Validation

Target Validation Info

References

Top

REF 1

Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)

REF 2

ClinicalTrials.gov (NCT03907969) A Clinical Trial to Evaluate AZD7648 Alone and in Combination With Other Anti-cancer Agents in Patients With Advanced Cancers.. U.S. National Institutes of Health.

REF 3

ClinicalTrials.gov (NCT03770689) Study of Peposertib in Combination With Capecitabine and Radiotherapy in Rectal Cancer. U.S. National Institutes of Health.

REF 4

AZD7648 is a potent and selective DNA-PK inhibitor that enhances radiation, chemotherapy and olaparib activity. Nat Commun. 2019 Nov 7;10(1):5065.

REF 5

Selective benzopyranone and pyrimido[2,1-a]isoquinolin-4-one inhibitors of DNA-dependent protein kinase: synthesis, structure-activity studies, and... J Med Chem. 2005 Jan 27;48(2):569-85.

REF 6

Pyranone, thiopyranone, and pyridone inhibitors of phosphatidylinositol 3-kinase related kinases. Structure-activity relationships for DNA-dependen... J Med Chem. 2007 Apr 19;50(8):1958-72.

REF 7

Identification of a highly potent and selective DNA-dependent protein kinase (DNA-PK) inhibitor (NU7441) by screening of chromenone libraries. Bioorg Med Chem Lett. 2004 Dec 20;14(24):6083-7.

REF 8

Discovery of potent chromen-4-one inhibitors of the DNA-dependent protein kinase (DNA-PK) using a small-molecule library approach. J Med Chem. 2005 Dec 1;48(24):7829-46.

REF 9

Inhibition 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.

REF 10

Modulation of DNA repair by pharmacological inhibitors of the PIKK protein kinase family. Bioorg Med Chem Lett. 2012 Sep 1;22(17):5352-9.

REF 11

1-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 12

A pharmacological map of the PI3-K family defines a role for p110alpha in insulin signaling. Cell. 2006 May 19;125(4):733-47.

REF 13

Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases. Nat Chem Biol. 2008 Nov;4(11):691-9.

REF 14

URL: 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).

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