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poly(ADP-ribose) polymerase 2

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Target not currently curated in GtoImmuPdb

Target id: 2772

Nomenclature: poly(ADP-ribose) polymerase 2

Abbreviated Name: PARP2

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 - 583 14q11.2 PARP2 poly(ADP-ribose) polymerase 2
Mouse - 559 14 C1 Parp2 poly (ADP-ribose) polymerase family, member 2
Rat - 558 15p14 Parp2 poly (ADP-ribose) polymerase 2
Previous and Unofficial Names Click here for help
poly (ADP-ribose) polymerase family, member 2 | poly (ADP-ribose) polymerase family | ADPRTL2 | poly (ADP-ribose) polymerase 2
Database Links Click here for help
Alphafold Q9UGN5 (Hs), O88554 (Mm)
BRENDA 2.4.2.30
CATH/Gene3D 1.20.142.10, 2.20.140.10
ChEMBL Target CHEMBL5366 (Hs), CHEMBL2794 (Mm)
Ensembl Gene ENSG00000129484 (Hs), ENSMUSG00000036023 (Mm), ENSRNOG00000008892 (Rn)
Entrez Gene 10038 (Hs), 11546 (Mm), 290027 (Rn)
Human Protein Atlas ENSG00000129484 (Hs)
KEGG Enzyme 2.4.2.30
KEGG Gene hsa:10038 (Hs), mmu:11546 (Mm), rno:290027 (Rn)
OMIM 607725 (Hs)
Pharos Q9UGN5 (Hs)
RefSeq Nucleotide NM_005484 (Hs), NM_009632 (Mm), NM_001106030 (Rn)
RefSeq Protein NP_005475 (Hs), NP_033762 (Mm), NP_001099500 (Rn)
SynPHARM 82672 (in complex with compound 10b [PMID: 26222319])
79918 (in complex with olaparib)
81954 (in complex with talazoparib)
UniProtKB Q9UGN5 (Hs), O88554 (Mm)
Wikipedia PARP2 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Structure of PARP2 catalytic domain bound to inhibitor BMN 673 (talazoparib)
PDB Id:  4PJV
Ligand:  talazoparib
Resolution:  2.5Å
Species:  Human
References:  1
Image of receptor 3D structure from RCSB PDB
Description:  Structure of PARP2 catalytic domain bound to an isoindolinone inhibitor
PDB Id:  4ZZX
Ligand:  compound 10b [PMID: 26222319]
Resolution:  1.65Å
Species:  Human
References:  9
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 6.9 pKd 9
⤷ pKd 6.9 (Kd 1.25x10-7 M) [9]
pamiparib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 9.1 pIC50 11
⤷ pIC50 9.1 (IC50 9x10-10 M) [11]
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 9.0 pIC50 2,5
⤷ pIC50 9.0 (IC50 1x10-9 M) [2,5]
Description: Assayed using PARP-2 isolated from HeLa cells, in a scintillation proximity ELISA.
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 Binding 8.7 pIC50 4
⤷ pIC50 8.7 (IC50 2.1x10-9 M) [4]
compound 5 [Tomassi et al., 2020] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.4 pIC50 10
⤷ pIC50 7.4 (IC50 3.78x10-8 M) [10]
AZ1366 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.6 pIC50 3
⤷ pIC50 6.6 (IC50 2.32x10-7 M) [3]
MC2050 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 5.7 – 6.3 pIC50 6,10
⤷ pIC50 6.3 (IC50 5.49x10-7 M) [10]
pIC50 5.7 (IC50 1.8x10-6 M) [6]
Description: Inhibitory effect of MC2050 in vitro on recombinant PARP2.
saruparib Small molecule or natural product Click here for species-specific activity table Hs Inhibition <5.8 pIC50 8
⤷ pIC50 <5.8 (IC50 >1.5x10-6 M) [8]
AZD9574 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 4.0 pIC50 7
⤷ pIC50 4.0 (IC50 9.3x10-5 M) [7]
talazoparib Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition - - 1
⤷ [1]

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. 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]

6. 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]

7. 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.

8. 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.

9. 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]

10. 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

11. 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 2. Last modified on 01/02/2023. Accessed on 16/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2772.