Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTQ4V96)

• DTT Name: Poly [ADP-ribose] polymerase 2 (PARP2)
• Synonyms: pADPRT-2; hPARP-2; Protein poly-ADP-ribosyltransferase PARP2; Poly[ADP-ribose] synthase 2; PARP-2; NAD(+) ADP-ribosyltransferase 2; DNA ADP-ribosyltransferase PARP2; ARTD2; ADPRTL2; ADPRT2; ADPRT-2; ADP-ribosyltransferase diphtheria toxin-like 2
• Gene Name: PARP2
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Glycosyltransferases
• UniProt ID: PARP2_HUMAN
• TTD ID: T40812
• EC Number: EC 2.4.2.30
• Sequence:
  MAARRRRSTGGGRARALNESKRVNNGNTAPEDSSPAKKTRRCQRQESKKMPVAGGKANKD
  RTEDKQDGMPGRSWASKRVSESVKALLLKGKAPVDPECTAKVGKAHVYCEGNDVYDVMLN
  QTNLQFNNNKYYLIQLLEDDAQRNFSVWMRWGRVGKMGQHSLVACSGNLNKAKEIFQKKF
  LDKTKNNWEDREKFEKVPGKYDMLQMDYATNTQDEEETKKEESLKSPLKPESQLDLRVQE
  LIKLICNVQAMEEMMMEMKYNTKKAPLGKLTVAQIKAGYQSLKKIEDCIRAGQHGRALME
  ACNEFYTRIPHDFGLRTPPLIRTQKELSEKIQLLEALGDIEIAIKLVKTELQSPEHPLDQ
  HYRNLHCALRPLDHESYEFKVISQYLQSTHAPTHSDYTMTLLDLFEVEKDGEKEAFREDL
  HNRMLLWHGSRMSNWVGILSHGLRIAPPEAPITGYMFGKGIYFADMSSKSANYCFASRLK
  NTGLLLLSEVALGQCNELLEANPKAEGLLQGKHSTKGLGKMAPSSAHFVTLNGSTVPLGP
  ASDTGILNPDGYTLNYNEYIVYNPNQVRMRYLLKVQFNFLQLW
• 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. ADP-ribosylation follows DNA damage and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks. Also mediates serine ADP-ribosylation of target proteins following interaction with HPF1; HPF1 conferring serine specificity. In addition to proteins, also able to ADP-ribosylate DNA: preferentially acts on 5'-terminal phosphates at DNA strand breaks termini in nicked duplex. Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair.
• KEGG Pathway:
  Base excision repair (hsa03410)
  Apoptosis (hsa04210)
  Necroptosis (hsa04217)
• Reactome Pathway:
  HDR through MMEJ (alt-NHEJ) (R-HSA-5685939)
  DNA Damage Recognition in GG-NER (R-HSA-5696394)
  Formation of Incision Complex in GG-NER (R-HSA-5696395)
  Dual Incision in GG-NER (R-HSA-5696400)
  POLB-Dependent Long Patch Base Excision Repair (R-HSA-110362)

Molecular Interaction Atlas (MIA) of This DTT

3 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID27841036-Compound-37	DM0OVZ2	Ovarian cancer	2C73	Phase 2	[1]
Stenoparib	DMKVBL8	Ovarian cancer	2C73	Phase 2	[2]
AMXI 5001	DMR9H6B	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[3]

3 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
3-phenyl isoquinolin-1(2H) derivative 1	DMB40HC	N. A.	N. A.	Patented	[1]
Dihydrodiazepinocarbazolone derivative 1	DMC3IN2	N. A.	N. A.	Patented	[1]
Tetra-cyclic pyridophthalazinone derivative 1	DMX2EFL	N. A.	N. A.	Patented	[1]

References

• [1] PARP inhibitors as antitumor agents: a patent update (2013-2015).Expert Opin Ther Pat. 2017 Mar;27(3):363-382.
• [2] Clinical pipeline report, company report or official report of Allarity Therapeutics.
• [3] AMXI-5001, a novel dual parp1/2 and microtubule polymerization inhibitor for the treatment of human cancers. Am J Cancer Res. 2020 Aug 1;10(8):2649-2676.