Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTVDSZ0)

• DTT Name: Poly [ADP-ribose] polymerase 1 (PARP1)
• Synonyms: Protein poly-ADP-ribosyltransferase PARP1; Poly[ADP-ribose] synthetase-1; Poly[ADP-ribose] synthase 1; Poly(ADP-ribose)polymerase-1; PPOL; PARP-1; NAD(+)Poly [ADP-ribose] polymerase-1 ADP-ribosyltransferase-1; NAD(+) ADP-ribosyltransferase-1; NAD(+) ADP-ribosyltransferase 1; DNA ADP-ribosyltransferase PARP1; ARTD1; ADPRT 1; ADPRT; ADP-ribosyltransferase diphtheria toxin-like 1
• Gene Name: PARP1
• DTT Type: Successful target; [1]
• BioChemical Class: Glycosyltransferases
• UniProt ID: PARP1_HUMAN
• TTD ID: T06273
• EC Number: EC 2.4.2.30
• Sequence:
  MAESSDKLYRVEYAKSGRASCKKCSESIPKDSLRMAIMVQSPMFDGKVPHWYHFSCFWKV
  GHSIRHPDVEVDGFSELRWDDQQKVKKTAEAGGVTGKGQDGIGSKAEKTLGDFAAEYAKS
  NRSTCKGCMEKIEKGQVRLSKKMVDPEKPQLGMIDRWYHPGCFVKNREELGFRPEYSASQ
  LKGFSLLATEDKEALKKQLPGVKSEGKRKGDEVDGVDEVAKKKSKKEKDKDSKLEKALKA
  QNDLIWNIKDELKKVCSTNDLKELLIFNKQQVPSGESAILDRVADGMVFGALLPCEECSG
  QLVFKSDAYYCTGDVTAWTKCMVKTQTPNRKEWVTPKEFREISYLKKLKVKKQDRIFPPE
  TSASVAATPPPSTASAPAAVNSSASADKPLSNMKILTLGKLSRNKDEVKAMIEKLGGKLT
  GTANKASLCISTKKEVEKMNKKMEEVKEANIRVVSEDFLQDVSASTKSLQELFLAHILSP
  WGAEVKAEPVEVVAPRGKSGAALSKKSKGQVKEEGINKSEKRMKLTLKGGAAVDPDSGLE
  HSAHVLEKGGKVFSATLGLVDIVKGTNSYYKLQLLEDDKENRYWIFRSWGRVGTVIGSNK
  LEQMPSKEDAIEHFMKLYEEKTGNAWHSKNFTKYPKKFYPLEIDYGQDEEAVKKLTVNPG
  TKSKLPKPVQDLIKMIFDVESMKKAMVEYEIDLQKMPLGKLSKRQIQAAYSILSEVQQAV
  SQGSSDSQILDLSNRFYTLIPHDFGMKKPPLLNNADSVQAKVEMLDNLLDIEVAYSLLRG
  GSDDSSKDPIDVNYEKLKTDIKVVDRDSEEAEIIRKYVKNTHATTHNAYDLEVIDIFKIE
  REGECQRYKPFKQLHNRRLLWHGSRTTNFAGILSQGLRIAPPEAPVTGYMFGKGIYFADM
  VSKSANYCHTSQGDPIGLILLGEVALGNMYELKHASHISKLPKGKHSVKGLGKTTPDPSA
  NISLDGVDVPLGTGISSGVNDTSLLYNEYIVYDIAQVNLKYLLKLKFNFKTSLW
• Function: Mainly mediates glutamate and aspartate ADP-ribosylation of target proteins: the ADP-D-ribosyl group of NAD(+) is transferred to the acceptor carboxyl group of glutamate and aspartate residues and further ADP-ribosyl groups are transferred to the 2'-position of the terminal adenosine moiety, building up a polymer with an average chain length of 20-30 units. Mediates the poly(ADP-ribosyl)ation of a number of proteins, including itself, APLF and CHFR. Also mediates serine ADP-ribosylation of target proteins following interaction with HPF1; HPF1 conferring serine specificity. Probably also catalyzes tyrosine ADP-ribosylation of target proteins following interaction with HPF1. Catalyzes the poly-ADP-ribosylation of histones in a HPF1-dependent manner. Involved in the base excision repair (BER) pathway by catalyzing the poly-ADP-ribosylation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. ADP-ribosylation follows DNA damage and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks. In addition to base excision repair (BER) pathway, also involved in double-strand breaks (DSBs) repair: together with TIMELESS, accumulates at DNA damage sites and promotes homologous recombination repair by mediating poly-ADP-ribosylation. In addition to proteins, also able to ADP-ribosylate DNA: catalyzes ADP-ribosylation of DNA strand break termini containing terminal phosphates and a 2'-OH group in single- and double-stranded DNA, respectively. Required for PARP9 and DTX3L recruitment to DNA damage sites. PARP1-dependent PARP9-DTX3L-mediated ubiquitination promotes the rapid and specific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites. Acts as a regulator of transcription: positively regulates the transcription of MTUS1 and negatively regulates the transcription of MTUS2/TIP150. With EEF1A1 and TXK, forms a complex that acts as a T-helper 1 (Th1) cell-specific transcription factor and binds the promoter of IFN-gamma to directly regulate its transcription, and is thus involved importantly in Th1 cytokine production. Involved in the synthesis of ATP in the nucleus, together with NMNAT1, PARG and NUDT5. Nuclear ATP generation is required for extensive chromatin remodeling events that are energy-consuming. Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair.
• KEGG Pathway:
  Base excision repair (hsa03410)
  NF-kappa B signaling pathway (hsa04064)
• Reactome Pathway: Dual Incision in GG-NER (R-HSA-5696400)

Molecular Interaction Atlas (MIA) of This DTT

3 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
KU-0058948	DMSA4HZ	Ovarian cancer	2C73	Approved	[2]
Nicotinamide	DMUPE07	Acne vulgaris	ED80	Approved	[1]
Niraparib Tosylate	DMLPSWQ	Fallopian tube cancer	2C74	Approved	[3]

8 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CC-486	DMTNQB0	Acute myeloid leukaemia	2A60	Phase 3	[4]
Nicaraven	DMFBNA3	Cerebrovascular disease	8B2Z	Phase 3	[5]
AG140699	DMA9FKY	Melanoma	2C30	Phase 2	[6]
AZD5305	DMW9R1C	Prostate cancer	2C82.0	Phase 2	[7]
PMID27841036-Compound-37	DM0OVZ2	Ovarian cancer	2C73	Phase 2	[8]
Stenoparib	DMKVBL8	Ovarian cancer	2C73	Phase 2	[9]
AMXI 5001	DMR9H6B	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[10]
NMS-03305293	DM2XIRW	Solid tumour/cancer	2A00-2F9Z	Phase 1	[11]

28 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
3-oxo-2,3-dihydro-1H-indazole-4-carboxamide derivative 1	DMAR2OX	N. A.	N. A.	Patented	[8]
3-oxo-2,3-dihydro-1H-indazole-4-carboxamide derivative 2	DMEVMU9	N. A.	N. A.	Patented	[8]
3-oxo-2,3-dihydro-1H-indazole-4-carboxamide derivative 3	DMRQ74I	N. A.	N. A.	Patented	[8]
3-oxo-2,3-dihydro-1H-indazole-4-carboxamide derivative 4	DM8Q19H	N. A.	N. A.	Patented	[8]
3-oxo-2,3-dihydro-1H-indazole-4-carboxamide derivative 5	DMXJ837	N. A.	N. A.	Patented	[8]
3-phenyl isoquinolin-1(2H) derivative 1	DMB40HC	N. A.	N. A.	Patented	[8]
3-phenyl isoquinolin-1(2H) derivative 2	DMA749P	N. A.	N. A.	Patented	[8]
4-Carboxamido-isoindolinone derivative 1	DMM9I1R	N. A.	N. A.	Patented	[8]
4-Carboxamido-isoindolinone derivative 2	DM3EHSN	N. A.	N. A.	Patented	[8]
4-Carboxamido-isoindolinone derivative 3	DM43YA0	N. A.	N. A.	Patented	[8]
4-Carboxamido-isoindolinone derivative 4	DMTGEFW	N. A.	N. A.	Patented	[8]
4-Carboxamido-isoindolinone derivative 5	DMIYVOC	N. A.	N. A.	Patented	[8]
7-azaindole derivative 8	DMO1920	N. A.	N. A.	Patented	[8]
Benzimidazole carboxamide derivative 1	DMB1L32	N. A.	N. A.	Patented	[8]
Dihydrodiazepinocarbazolone derivative 1	DMC3IN2	N. A.	N. A.	Patented	[8]
Dihydropyrido phthalazinone derivative 1	DMWIYFQ	N. A.	N. A.	Patented	[8]
Dihydropyrido phthalazinone derivative 2	DMR4PQN	N. A.	N. A.	Patented	[8]
Phthalazine derivative 3	DMA1OEF	N. A.	N. A.	Patented	[8]
Phthalazine ketone derivative 1	DMD2R1H	N. A.	N. A.	Patented	[8]
Phthalazine ketone derivative 2	DM07C1I	N. A.	N. A.	Patented	[8]
Phthalazine ketone derivative 3	DMIWY93	N. A.	N. A.	Patented	[8]
PMID27841036-Compound-33	DMGXI95	N. A.	N. A.	Patented	[8]
Quinazolinedione derivative 1	DMSD04W	N. A.	N. A.	Patented	[8]
Quinazolinedione derivative 2	DM3TVI6	N. A.	N. A.	Patented	[8]
Quinazolinedione derivative 3	DMZ5GIH	N. A.	N. A.	Patented	[8]
Tetra-cyclic pyridophthalazinone derivative 1	DMX2EFL	N. A.	N. A.	Patented	[8]
Tetra-hydro-quinoline derivative 1	DMM92KW	N. A.	N. A.	Patented	[8]
Tricyclic indole compound 13	DMS6XT4	N. A.	N. A.	Patented	[8]

2 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CPH-102	DMQGRC8	Solid tumour/cancer	2A00-2F9Z	Preclinical	[12]
PJ34	DMXO6YH	Coronavirus infection	1D92	Preclinical	[13]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
NU1025	DMPA8WO	N. A.	N. A.	Terminated	[14]

89 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(E)-N-(4-Phenylthiazol-2-yl) cinnamamide	DM7XIH3	Discovery agent	N.A.	Investigative	[15]
1,2,3,4,4a,5-hexahydrophenanthridin-6(10bH)-one	DM7JMCI	Discovery agent	N.A.	Investigative	[15]
1,7,8,9-tetrahydro-1,5-diaza-trindene-4,6-dione	DMBU796	Discovery agent	N.A.	Investigative	[16]
2,3-dihydro-1H-benzo[de]isoquinolin-1-one	DMB3WI8	Discovery agent	N.A.	Investigative	[17]
2,8-Dimethyl-3H-quinazolin-4-one	DMU2EFH	Discovery agent	N.A.	Investigative	[18]
2-(2-Chlorophenyl)-2H-indazole-7-carboxamide	DMTYDX2	Discovery agent	N.A.	Investigative	[19]
2-(3'-Methoxyphenyl) Benzimidazole-4-Carboxamide	DMCDGAU	Discovery agent	N.A.	Investigative	[14]
2-(3-Chlorophenyl)-2H-indazole-7-carboxamide	DMYQBSV	Discovery agent	N.A.	Investigative	[19]
2-(3-Piperidin-1-yl-propyl)-3H-quinazolin-4-one	DMZ5H8O	Discovery agent	N.A.	Investigative	[20]
2-(4-Amino-phenyl)-8-hydroxy-3H-quinazolin-4-one	DM7LBEG	Discovery agent	N.A.	Investigative	[18]
2-(4-Amino-phenyl)-8-methyl-3H-quinazolin-4-one	DMJRDAQ	Discovery agent	N.A.	Investigative	[18]
2-(4-Azido-phenyl)-8-methoxy-3H-quinazolin-4-one	DM2JG49	Discovery agent	N.A.	Investigative	[18]
2-(4-Chlorophenyl)-2H-indazole-7-carboxamide	DM6Z9U4	Discovery agent	N.A.	Investigative	[19]
2-(4-Chlorophenyl)-5-Quinoxalinecarboxamide	DM9SGBO	Discovery agent	N.A.	Investigative	[21]
2-(4-Hydroxy-phenyl)-8-methyl-3H-quinazolin-4-one	DMVHQM9	Discovery agent	N.A.	Investigative	[18]
2-(4-Methoxy-phenyl)-8-methyl-3H-quinazolin-4-one	DMS572H	Discovery agent	N.A.	Investigative	[18]
2-(4-methoxyphenyl)quinoline-8-carboxamide	DMBRETS	Discovery agent	N.A.	Investigative	[22]
2-Benzyl-2H-indazole-7-carboxamide	DMPYB93	Discovery agent	N.A.	Investigative	[19]
2-ethylquinoline-8-carboxamide	DMKR47X	Discovery agent	N.A.	Investigative	[22]
2-Methylquinoline-8-carboxamide	DMUN3LV	Discovery agent	N.A.	Investigative	[22]
2-phenyl-2H-benzo[d][1,2,3]triazole-4-carboxamide	DMTSBJL	Discovery agent	N.A.	Investigative	[19]
2-phenyl-2H-indazole-7-carboxamide	DM8HSMU	Discovery agent	N.A.	Investigative	[19]
2-phenylpyrazolo-[1,5-a]pyridine-7-carboxamide	DM64JE8	Discovery agent	N.A.	Investigative	[19]
2-phenylquinoline-8-carboxamide	DMAENRQ	Discovery agent	N.A.	Investigative	[22]
2H-Isoquinolin-1-one	DMHR1UE	Discovery agent	N.A.	Investigative	[18]
3-(4-aminophenyl)quinoxaline-5-carboxamide	DM6XTBI	Discovery agent	N.A.	Investigative	[15]
3-(4-cyanophenyl)quinoxaline-5-carboxamide	DM23JIY	Discovery agent	N.A.	Investigative	[15]
3-(4-methoxyphenyl)quinoxaline-5-carboxamide	DM7WPQC	Discovery agent	N.A.	Investigative	[15]
3-aminobenzamide	DM7P3IZ	Discovery agent	N.A.	Investigative	[13]
3-aminobenzo[c][1,5]naphthyridin-6(5H)-one	DML2UCP	Discovery agent	N.A.	Investigative	[15]
3-Ethenylquinoline-8-carboxamide	DMTKQNU	Discovery agent	N.A.	Investigative	[22]
3-Ethylquinoline-8-carboxamide	DMGPRBE	Discovery agent	N.A.	Investigative	[22]
3-Ethynylquinoline-8-carboxamide	DMS4JGT	Discovery agent	N.A.	Investigative	[22]
3-Hydroxy-benzamide	DMNV1P3	Discovery agent	N.A.	Investigative	[18]
3-Methoxybenzamide	DM245AB	Discovery agent	N.A.	Investigative	[21]
3-Methylquinoline-8-carboxamide	DMQZULR	Discovery agent	N.A.	Investigative	[22]
3-Morpholin-4-ylmethyl-5H-phenanthridin-6-one	DM0YS25	Discovery agent	N.A.	Investigative	[23]
3-Phenylquinoline-8-carboxamide	DM12SKU	Discovery agent	N.A.	Investigative	[22]
3-Prop-1-ynylquinoline-8-carboxamide	DM23I8E	Discovery agent	N.A.	Investigative	[22]
4-(4-Morpholin-4-yl-butyl)-2H-phthalazin-1-one	DMS74F2	Discovery agent	N.A.	Investigative	[23]
4-(5-Morpholin-4-yl-pentyl)-2H-phthalazin-1-one	DMXHIK5	Discovery agent	N.A.	Investigative	[23]
4-amino-1,8-naphthalimide	DMU49H6	Discovery agent	N.A.	Investigative	[14]
4-benzylphthalazin-1(2H)-one	DMA5FEM	Discovery agent	N.A.	Investigative	[15]
4-methylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione	DMVMHBL	Discovery agent	N.A.	Investigative	[16]
5-amino-3,4-dihydroisoquinolin-1(2H)-one	DMR853M	Discovery agent	N.A.	Investigative	[17]
5-aminoisoquinolin-1(2H)-one	DMVPSXW	Discovery agent	N.A.	Investigative	[22]
5-Chloro-2-methyl-3H-quinazolin-4-one	DM6YBZR	Discovery agent	N.A.	Investigative	[20]
5-methylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione	DMYERNM	Discovery agent	N.A.	Investigative	[16]
8-Amino-6H,11H-indeno[1,2-c]isoquinolin-5-one	DMTRBDP	Discovery agent	N.A.	Investigative	[24]
8-Fluoro-6H,11H-indeno[1,2-c]isoquinolin-5-one	DMKPMFJ	Discovery agent	N.A.	Investigative	[24]
8-Hydroxy-2-(4-nitro-phenyl)-3H-quinazolin-4-one	DMNE52B	Discovery agent	N.A.	Investigative	[18]
8-Hydroxy-2-phenyl-3H-quinazolin-4-one	DMKD2Q4	Discovery agent	N.A.	Investigative	[18]
8-Methoxy-2-(4-nitro-phenyl)-3H-quinazolin-4-one	DMSN0ZE	Discovery agent	N.A.	Investigative	[18]
8-Methoxy-2-methyl-3H-quinazolin-4-one	DMOPN4K	Discovery agent	N.A.	Investigative	[18]
8-Methoxy-2-phenyl-3H-quinazolin-4-one	DM56EW7	Discovery agent	N.A.	Investigative	[18]
8-Methyl-2-(4-nitro-phenyl)-3H-quinazolin-4-one	DM7FSZM	Discovery agent	N.A.	Investigative	[18]
8-Methyl-2-phenyl-3H-quinazolin-4-one	DMEM6Q0	Discovery agent	N.A.	Investigative	[18]
8-Nitro-6H,11H-indeno[1,2-c]isoquinolin-5-one	DM5L40C	Discovery agent	N.A.	Investigative	[24]
9-Amino-6H,11H-indeno[1,2-c]isoquinolin-5-one	DMUL6QR	Discovery agent	N.A.	Investigative	[24]
9-Fluoro-6H,11H-indeno[1,2-c]isoquinolin-5-one	DMGAE9Z	Discovery agent	N.A.	Investigative	[24]
A-620223	DM9SXDI	Solid tumour/cancer	2A00-2F9Z	Investigative	[12]
AG-014376	DMHFYNE	Discovery agent	N.A.	Investigative	[25]
ANG-2684	DMDLVH5	Cerebrovascular ischaemia	8B1Z	Investigative	[12]
ANG-2864	DMQ2TNL	Solid tumour/cancer	2A00-2F9Z	Investigative	[12]
Benzo[c][1,5]naphthyridin-6(5H)-one	DMMYGB9	Discovery agent	N.A.	Investigative	[15]
BPI-704001	DMGQXTR	Solid tumour/cancer	2A00-2F9Z	Investigative	[12]
BZ3	DMN5X17	Discovery agent	N.A.	Investigative	[26]
BZ5	DMRXPFM	Discovery agent	N.A.	Investigative	[26]
BZ6	DMF8UWE	Ataxia-telangiectasia	4A01.31	Investigative	[26]
Carba-Nicotinamide-Adenine-Dinucleotide	DMGP4M3	Discovery agent	N.A.	Investigative	[21]
CEP-6800	DMS16BD	Discovery agent	N.A.	Investigative	[27]
DR2313	DM1AV5R	Stroke	8B20	Investigative	[6]
EB-47	DM4UZ6V	Discovery agent	N.A.	Investigative	[6]
HYDAMTIQ	DMY5RDI	Brain ischaemia	8B1Z	Investigative	[12]
INO-1002	DMZEXY9	Solid tumour/cancer	2A00-2F9Z	Investigative	[12]
KR-33889	DMC4YGT	Myocardial infarction	BA41-BA43	Investigative	[12]
KU-58684	DMVGY6K	Discovery agent	N.A.	Investigative	[15]
ME0328	DMCLT1V	Discovery agent	N.A.	Investigative	[28]
N-(4-Phenylthiazol-2-yl)isonicotinamide	DM2OHVJ	Discovery agent	N.A.	Investigative	[15]
PD-128763	DMV1F7U	Discovery agent	N.A.	Investigative	[21]
Pyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione	DM1X5JR	Discovery agent	N.A.	Investigative	[16]
Pyrrolo[3,4-e]indole-1,3(2H,6H)-dione	DMM4CU9	Discovery agent	N.A.	Investigative	[16]
Quinoline-8-carboxamide	DMV57OZ	Discovery agent	N.A.	Investigative	[22]
S-070	DMANSCK	Solid tumour/cancer	2A00-2F9Z	Investigative	[12]
S-111	DMRVUCY	Solid tumour/cancer	2A00-2F9Z	Investigative	[12]
Thieno-phenanthridin-6-one	DMFDROW	Brain ischaemia	8B1Z	Investigative	[6]
TI3	DMGXSTB	Discovery agent	N.A.	Investigative	[26]
TI4	DMOXINT	Discovery agent	N.A.	Investigative	[26]
[2(R,S)-2-Sulfanylheptanoyl]-Phe-Ala	DMI9RLZ	Discovery agent	N.A.	Investigative	[26]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Ovarian cancer	2C82	Ovarian tissue	5.01E-05	1.02	2.68
Melanoma	2C82	Skin	4.17E-08	0.85	2.21
Lung cancer	2C82	Lung tissue	1.62E-122	0.77	3
Breast cancer	2C82	Breast tissue	1.53E-134	0.88	2.45
Neuroectodermal tumour	2C82	Nervous tissue	2.09E-31	0.26	0.88

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