Top ▲

poly(ADP-ribose) polymerase 1

Click here for help

Target not currently curated in GtoImmuPdb

Target id: 2771

Nomenclature: poly(ADP-ribose) polymerase 1

Abbreviated Name: PARP1

Family: Poly ADP-ribose polymerases

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 1014 1q42.12 PARP1 poly(ADP-ribose) polymerase 1
Mouse - 1013 1 84.44 cM Parp1 poly (ADP-ribose) polymerase family, member 1
Rat - 1014 13q26 Parp1 poly (ADP-ribose) polymerase 1
Previous and Unofficial Names Click here for help
poly (ADP-ribose) polymerase family, member 1 | poly (ADP-ribose) polymerase family | ADP-ribosyltransferase | ADPRT | poly (ADP-ribose) polymerase 1 | PPOL
Database Links Click here for help
BRENDA
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Structure of PARP1 catalytic domain bound to inhibitor BMN 673 (talazoparib)
PDB Id:  4PJT
Ligand:  talazoparib
Resolution:  2.35Å
Species:  Human
References:  1
Image of receptor 3D structure from RCSB PDB
Description:  Structure of human PARP1 catalytic domain bound to an isoindolinone inhibitor
PDB Id:  4ZZZ
Ligand:  compound 10b [PMID: 26222319]
Resolution:  1.9Å
Species:  Human
References:  10
Enzyme Reaction Click here for help
EC Number: 2.4.2.30

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
compound 10b [PMID: 26222319] Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.1 pKd 10
pKd 7.1 (Kd 8.7x10-8 M) [10]
rucaparib Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Hs Inhibition 8.9 pKi 12
pKi 8.9 (Ki 1.4x10-9 M) [12]
AG14361 Small molecule or natural product Primary target of this compound Hs Inhibition 8.2 pKi 11
pKi 8.2 (Ki 5.8x10-9 M) [11]
niraparib Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.4 pIC50 4
pIC50 8.4 (IC50 3.8x10-9 M) [4]
olaparib Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.3 pIC50 2,7
pIC50 8.3 (IC50 5x10-9 M) [2,7]
Description: Assayed using PARP-1 isolated from HeLa cells, in a scintillation proximity ELISA.
venadaparib Small molecule or natural product Hs Inhibition >8.3 pIC50 5
pIC50 >8.3 (IC50 <5x10-9 M) [5]
Description: Measuring cellular PARP inhibitory activity in a cellular PAR assay.
PJ34 Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 7.7 pIC50 8
pIC50 7.7 (IC50 2x10-8 M) [8]
MC2050 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.9 – 8.0 pIC50 9,13
pIC50 8.0 (IC50 9.3x10-9 M) [13]
pIC50 6.9 (IC50 1.19x10-7 M) [9]
Description: inhibitory capacity of MC2050 in vitro on recombinant PARP1.
compound 5 [Tomassi et al., 2020] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.1 pIC50 13
pIC50 7.1 (IC50 8.96x10-8 M) [13]
ciclopirox Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibition 6.8 pIC50 8
pIC50 6.8 (IC50 1.6x10-7 M) [8]
AZ1366 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.3 pIC50 3
pIC50 6.3 (IC50 5.59x10-7 M) [3]
ME0328 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 5.2 pIC50 6
pIC50 5.2 (IC50 6.3x10-6 M) [6]
talazoparib Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition - - 1
[1]
Immuno Process Associations
Immuno Process:  Immune system development
GO Annotations:  Associated to 1 GO processes
GO:0030225 macrophage differentiation TAS
Immuno Process:  Cytokine production & signalling

References

Show »

1. Aoyagi-Scharber M, Gardberg AS, Yip BK, Wang B, Shen Y, Fitzpatrick PA. (2014) Structural basis for the inhibition of poly(ADP-ribose) polymerases 1 and 2 by BMN 673, a potent inhibitor derived from dihydropyridophthalazinone. Acta Crystallogr F Struct Biol Commun, 70 (Pt 9): 1143-9. [PMID:25195882]

2. Dillon KJ, Smith GC, Martin NM. (2003) A FlashPlate assay for the identification of PARP-1 inhibitors. J Biomol Screen, 8 (3): 347-52. [PMID:12857389]

3. Johannes JW, Almeida L, Barlaam B, Boriack-Sjodin PA, Casella R, Croft RA, Dishington AP, Gingipalli L, Gu C, Hawkins JL et al.. (2015) Pyrimidinone nicotinamide mimetics as selective tankyrase and wnt pathway inhibitors suitable for in vivo pharmacology. ACS Med Chem Lett, 6 (3): 254-9. [PMID:25815142]

4. Jones P, Altamura S, Boueres J, Ferrigno F, Fonsi M, Giomini C, Lamartina S, Monteagudo E, Ontoria JM, Orsale MV et al.. (2009) Discovery of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide (MK-4827): a novel oral poly(ADP-ribose)polymerase (PARP) inhibitor efficacious in BRCA-1 and -2 mutant tumors. J Med Chem, 52 (22): 7170-85. [PMID:19873981]

5. Kang J-H, Lee H-S, Lee Y-S, Park J-T, An K-M, Jeong J-A, Kim K-S, Kim J-G, Hong C-H, Park S-Y et al.. (2015) A novel phtalazinone derivatives and manufacturing process thereof. Patent number: WO2015037939A1. Assignee: Ildong Pharm Co., Ltd.. Priority date: 13/09/2013. Publication date: 19/03/2015.

6. Lindgren AE, Karlberg T, Ekblad T, Spjut S, Thorsell AG, Andersson CD, Nhan TT, Hellsten V, Weigelt J, Linusson A et al.. (2013) Chemical probes to study ADP-ribosylation: synthesis and biochemical evaluation of inhibitors of the human ADP-ribosyltransferase ARTD3/PARP3. J Med Chem, 56 (23): 9556-68. [PMID:24188023]

7. Menear KA, Adcock C, Boulter R, Cockcroft XL, Copsey L, Cranston A, Dillon KJ, Drzewiecki J, Garman S, Gomez S et al.. (2008) 4-[3-(4-cyclopropanecarbonylpiperazine-1-carbonyl)-4-fluorobenzyl]-2H-phthalazin-1-one: a novel bioavailable inhibitor of poly(ADP-ribose) polymerase-1. J Med Chem, 51 (20): 6581-91. [PMID:18800822]

8. Moree WJ, Goldman P, Demaggio AJ, Christenson E, Herendeen D, Eksterowicz J, Kesicki EA, McElligott DL, Beaton G. (2008) Identification of ring-fused pyrazolo pyridin-2-ones as novel poly(ADP-ribose)polymerase-1 inhibitors. Bioorg Med Chem Lett, 18 (18): 5126-9. [PMID:18713665]

9. Mosca L, Rotili D, Tempera I, Masci A, Fontana M, Chiaraluce R, Mastromarino P, d'Erme M, Mai A. (2011) Biological effects of MC2050, a quinazoline-based PARP-1 inhibitor, in human neuroblastoma and EBV-positive Burkitt's lymphoma cells. ChemMedChem, 6 (4): 606-11. [PMID:21365766]

10. Papeo G, Posteri H, Borghi D, Busel AA, Caprera F, Casale E, Ciomei M, Cirla A, Corti E, D'Anello M et al.. (2015) Discovery of 2-[1-(4,4-Difluorocyclohexyl)piperidin-4-yl]-6-fluoro-3-oxo-2,3-dihydro-1H-isoindole-4-carboxamide (NMS-P118): A Potent, Orally Available, and Highly Selective PARP-1 Inhibitor for Cancer Therapy. J Med Chem, 58 (17): 6875-98. [PMID:26222319]

11. Skalitzky DJ, Marakovits JT, Maegley KA, Ekker A, Yu XH, Hostomsky Z, Webber SE, Eastman BW, Almassy R, Li J et al.. (2003) Tricyclic benzimidazoles as potent poly(ADP-ribose) polymerase-1 inhibitors. J Med Chem, 46 (2): 210-3. [PMID:12519059]

12. Thomas HD, Calabrese CR, Batey MA, Canan S, Hostomsky Z, Kyle S, Maegley KA, Newell DR, Skalitzky D, Wang LZ et al.. (2007) Preclinical selection of a novel poly(ADP-ribose) polymerase inhibitor for clinical trial. Mol Cancer Ther, 6 (3): 945-56. [PMID:17363489]

13. Tomassi S, Pfahler J, Mautone N, Rovere A, Esposito C, Passeri D, Pellicciari R, Novellino E, Pannek M, Steegborn C et al.. (2020) From PARP1 to TNKS2 Inhibition: A Structure-Based Approach. ACS Med Chem Lett, [Articles ASAP]. DOI: 10.1021/acsmedchemlett.9b00654

How to cite this page

Poly ADP-ribose polymerases: poly(ADP-ribose) polymerase 1. Last modified on 14/12/2020. Accessed on 11/05/2021. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2771.