poly(ADP-ribose) polymerase 1 | Poly ADP-ribose polymerases | IUPHAR/BPS Guide to PHARMACOLOGY

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poly(ADP-ribose) polymerase 1

Target not currently curated in GtoImmuPdb

Target id: 2771

Nomenclature: poly(ADP-ribose) polymerase 1

Abbreviated Name: PARP1

Family: Poly ADP-ribose polymerases

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 1014 1q41-q42 PARP1 poly(ADP-ribose) polymerase 1
Mouse - 1014 1 H5 Parp1 poly (ADP-ribose) polymerase family
Rat - 1014 13q26 Parp1 poly (ADP-ribose) polymerase 1
Previous and Unofficial Names
poly (ADP-ribose) polymerase family, member 1 | poly (ADP-ribose) polymerase family | ADP-ribosyltransferase | ADPRT | poly (ADP-ribose) polymerase 1 | PPOL
Database Links
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
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:  8
Enzyme Reaction
EC Number: 2.4.2.30

Download all structure-activity data for this target as a CSV file

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] Hs Inhibition 7.1 pKd 8
pKd 7.1 (Kd 8.7x10-8 M) [8]
rucaparib Hs Inhibition 8.9 pKi 10
pKi 8.9 (Ki 1.4x10-9 M) [10]
AG14361 Hs Inhibition 8.2 pKi 9
pKi 8.2 (Ki 5.8x10-9 M) [9]
niraparib Hs Binding 8.4 pIC50 4
pIC50 8.4 (IC50 3.8x10-9 M) [4]
olaparib Hs Inhibition 8.3 pIC50 2,6
pIC50 8.3 (IC50 5x10-9 M) [2,6]
Description: Assayed using PARP-1 isolated from HeLa cells, in a scintillation proximity ELISA.
MC2050 Hs Inhibition 6.9 – 8.0 pIC50 7,11
pIC50 8.0 (IC50 9.3x10-9 M) [11]
pIC50 6.9 (IC50 1.19x10-7 M) [7]
Description: inhibitory capacity of MC2050 in vitro on recombinant PARP1.
compound 5 [Tomassi et al., 2020] Hs Inhibition 7.1 pIC50 11
pIC50 7.1 (IC50 8.96x10-8 M) [11]
AZ1366 Hs Inhibition 6.3 pIC50 3
pIC50 6.3 (IC50 5.59x10-7 M) [3]
ME0328 Hs Inhibition 5.2 pIC50 5
pIC50 5.2 (IC50 6.3x10-6 M) [5]
talazoparib 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
GO Annotations:  Associated to 1 GO processes
GO:1905077 negative regulation of interleukin-17 secretion IMP

References

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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. 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]

6. 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]

7. 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]

8. 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]

9. 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]

10. 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]

11. 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 14/02/2020. Accessed on 07/06/2020. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2771.