Top ▲

poly(ADP-ribose) polymerase 1

Click here for help

Target id: 2771

Nomenclature: poly(ADP-ribose) polymerase 1

Abbreviated Name: PARP1

Family: Poly ADP-ribosylating PARPs

Contents:

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
Alphafold P09874 (Hs), P11103 (Mm), P27008 (Rn)
BRENDA 2.4.2.30
CATH/Gene3D 2.20.140.10, 3.30.1740.10, 3.40.50.10190, 1.20.142.10
ChEMBL Target CHEMBL3105 (Hs), CHEMBL3740 (Mm), CHEMBL4664 (Rn)
Ensembl Gene ENSG00000143799 (Hs), ENSMUSG00000026496 (Mm), ENSRNOG00000003084 (Rn)
Entrez Gene 142 (Hs), 11545 (Mm), 25591 (Rn)
Human Protein Atlas ENSG00000143799 (Hs)
KEGG Enzyme 2.4.2.30
KEGG Gene hsa:142 (Hs), mmu:11545 (Mm), rno:25591 (Rn)
OMIM 173870 (Hs)
Pharos P09874 (Hs)
RefSeq Nucleotide NM_001618 (Hs), NM_007415 (Mm), NM_013063 (Rn)
RefSeq Protein NP_001609 (Hs), NP_031441 (Mm), NP_037195 (Rn)
SynPHARM 82673 (in complex with compound 10b [PMID: 26222319])
81911 (in complex with niraparib)
79917 (in complex with olaparib)
80263 (in complex with rucaparib)
81953 (in complex with talazoparib)
UniProtKB P09874 (Hs), P11103 (Mm), P27008 (Rn)
Wikipedia PARP1 (Hs)
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:  16
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
KU0058948 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.7 pKd 7
⤷ pKd 7.7 (Kd 1.9x10-8 M) [7]
Description: Binding affinity determined by isothermal titration calorimetry.
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 16
⤷ pKd 7.1 (Kd 8.7x10-8 M) [16]
rucaparib Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Hs Inhibition 8.9 pKi 18
⤷ pKi 8.9 (Ki 1.4x10-9 M) [18]
AG14361 Small molecule or natural product Primary target of this compound Hs Inhibition 8.2 pKi 17
⤷ pKi 8.2 (Ki 5.8x10-9 M) [17]
pamiparib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.9 pIC50 20
⤷ pIC50 8.9 (IC50 1.3x10-9 M) [20]
lerzeparib Small molecule or natural product Hs Inhibition 8.6 pIC50 3
⤷ pIC50 8.6 (IC50 2.8x10-9 M) [3]
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 5
⤷ pIC50 8.4 (IC50 3.8x10-9 M) [5]
saruparib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.4 pIC50 15
⤷ pIC50 8.4 (IC50 4x10-9 M) [15]
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 2,11
⤷ pIC50 8.3 (IC50 5x10-9 M) [2,11]
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 6
⤷ pIC50 >8.3 (IC50 <5x10-9 M) [6]
Description: Measuring cellular PARP inhibitory activity in a cellular PAR assay.
AZD9574 Small molecule or natural product Click here for species-specific activity table Hs Inhibition >8.3 pIC50 14
⤷ pIC50 >8.3 (IC50 <5x10-9 M) [14]
PJ34 Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 7.7 pIC50 12
⤷ pIC50 7.7 (IC50 2x10-8 M) [12]
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 13,19
⤷ pIC50 8.0 (IC50 9.3x10-9 M) [19]
pIC50 6.9 (IC50 1.19x10-7 M) [13]
Description: inhibitory capacity of MC2050 in vitro on recombinant PARP1.
dual VEGFR/PARP inhibitor 14b Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.2 pIC50 8
⤷ pIC50 7.2 (IC50 6.09x10-8 M) [8]
compound 5 [Tomassi et al., 2020] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.1 pIC50 19
⤷ pIC50 7.1 (IC50 8.96x10-8 M) [19]
ciclopirox Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibition 6.8 pIC50 12
⤷ pIC50 6.8 (IC50 1.6x10-7 M) [12]
AZ1366 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.3 pIC50 4
⤷ pIC50 6.3 (IC50 5.59x10-7 M) [4]
ME0328 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 5.2 pIC50 10
⤷ pIC50 5.2 (IC50 6.3x10-6 M) [10]
talazoparib Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition - - 1
⤷ [1]
compound 9 [Lin et al., 2023] Small molecule or natural product Hs Inhibition - - 9
⤷ [9]
Immuno Process Associations
Immuno Process:  Immune system development
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. Hu Y, Li G, Sun F, Chi Z, Luo J, Ding CZ, Chen S. (2022) Indolo heptamyl oxime analogue as parp inhibitor. Patent number: US20220144850A1. Assignee: Chia Tai Tianqing Pharmaceutical Group Co Ltd. Priority date: 03/02/2020. Publication date: 12/05/2022.

4. 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]

5. 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]

6. 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.

7. Lehtiö L, Jemth AS, Collins R, Loseva O, Johansson A, Markova N, Hammarström M, Flores A, Holmberg-Schiavone L, Weigelt J et al.. (2009) Structural basis for inhibitor specificity in human poly(ADP-ribose) polymerase-3. J Med Chem, 52 (9): 3108-11. [PMID:19354255]

8. Li Y, Liu Y, Zhang D, Chen J, Yang G, Tang P, Yang C, Liu J, Zhang J, Ouyang L. (2023) Discovery, Synthesis, and Evaluation of Novel Dual Inhibitors of a Vascular Endothelial Growth Factor Receptor and Poly(ADP-Ribose) Polymerase for BRCA Wild-Type Breast Cancer Therapy. J Med Chem, 66 (17): 12069-12100. [PMID:37616488]

9. Lin S, Jiang Q, Huang X, Xu J, Wu L, Liu Y. (2023) Synthesis of Novel Dual Target Inhibitors of CDK12 and PARP1 and Their Antitumor Activities in HER2-Positive Breast Cancers. ACS Omega,. DOI: 10.1021/acsomega.3c02912

10. 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]

11. 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]

12. 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]

13. 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]

14. Packer MJ, Degore SL, Johannes JW, Hande SM, Ghosh A, Zheng X. (2021) Quinoxaline derivatives as anti-cancer drugs. Patent number: WO2021260092A1. Assignee: Astrazeneca Ab. Priority date: 25/06/2020. Publication date: 31/12/2021.

15. Packer MJ, Johannes JW, Hande SM, Degorce SL. (2021) PARP1 INHIBITORS. Patent number: WO2021013735. Assignee: ASTRAZENECA. Priority date: 27/04/2021. Publication date: 19/07/2019.

16. 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]

17. 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]

18. 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]

19. 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

20. Wang H, Ren B, Liu Y, Jiang B, Guo Y, Wei M, Luo L, Kuang X, Qiu M, Lv L et al.. (2020) Discovery of Pamiparib (BGB-290), a Potent and Selective Poly (ADP-ribose) Polymerase (PARP) Inhibitor in Clinical Development. J Med Chem, 63 (24): 15541-15563. [PMID:33264017]

How to cite this page

Poly ADP-ribosylating PARPs: poly(ADP-ribose) polymerase 1. Last modified on 24/01/2024. Accessed on 16/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2771.