Target Information

Target General Information

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Target ID

T34867

Target Name

Poly [ADP-ribose] polymerase (PARP)

Synonyms

Poly-ADP-ribose polymerase

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Gene Name

NO-GeName

Target Type

Successful target

[1]

Disease

[+] 2 Target-related Diseases

Breast cancer [ICD-11: 2C60-2C6Y]

Ovarian cancer [ICD-11: 2C73]

UniProt ID

NOUNIPROTAC

Drugs and Modes of Action

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Approved Drug(s)

[+] 3 Approved Drugs

Olaparib

Drug Info

Approved

Ovarian cancer

[2], [3]

Rucaparib

Drug Info

Approved

Ovarian cancer

[4]

Talazoparib

Drug Info

Approved

Breast cancer

[5]

Clinical Trial Drug(s)

[+] 13 Clinical Trial Drugs

ABT-888

Drug Info

Phase 3

Breast cancer

[6], [7], [8]

BSI-201

Drug Info

Phase 3

Solid tumour/cancer

[9], [10]

INO-1001

Drug Info

Phase 3

Brain cancer

[11], [12]

MK-4827

Drug Info

Phase 3

Ovarian cancer

[13]

Rubraca rucaparib

Drug Info

Phase 3

Prostate cancer

[8]

2X-121

Drug Info

Phase 2

Breast cancer

[8]

AZD9574

Drug Info

Phase 2

Aggressive cancer

[14]

BGB-290

Drug Info

Phase 2

Ovarian cancer

[15]

BGP-15

Drug Info

Phase 2

Type-2 diabetes

[16], [17], [18]

E7016

Drug Info

Phase 2

Melanoma

[19]

CEP-9722

Drug Info

Phase 1/2

Non-small-cell lung cancer

[20]

ABT-767

Drug Info

Phase 1

Solid tumour/cancer

[21]

MP-124

Drug Info

Phase 1

Ischemic stroke

[22]

Discontinued Drug(s)

[+] 1 Discontinued Drugs

ONO-2231

Drug Info

Discontinued in Phase 1

Cerebrovascular ischaemia

[23]

Mode of Action

[+] 2 Modes of Action

Modulator

[+] 12 Modulator drugs

Olaparib

Drug Info

[1]

Rucaparib

Drug Info

[4]

ABT-888

Drug Info

[24]

BSI-201

Drug Info

[10]

INO-1001

Drug Info

[11], [12]

MK-4827

Drug Info

[24]

BGP-15

Drug Info

[16], [17]

E7016

Drug Info

[24]

CEP-9722

Drug Info

[24]

ABT-767

Drug Info

[24]

MP-124

Drug Info

[27]

ONO-2231

Drug Info

[29]

Inhibitor

[+] 20 Inhibitor drugs

Talazoparib

Drug Info

[5]

Rubraca rucaparib

Drug Info

[8]

2X-121

Drug Info

[8]

AZD9574

Drug Info

[25]

BGB-290

Drug Info

[8], [26]

7-azaindole derivative 9

Drug Info

[28]

Aza-phenalene-3-ketone derivative 1

Drug Info

[28]

Dihydrodiazepinocarbazolone derivative 2

Drug Info

[28]

Dihydropyrido phthalazinone derivative 3

Drug Info

[28]

Dihydropyrido phthalazinone derivative 4

Drug Info

[28]

Phthalazine derivative 1

Drug Info

[28]

Phthalazine derivative 2

Drug Info

[28]

PMID27841036-Compound-23

Drug Info

[28]

PMID27841036-Compound-24

Drug Info

[28]

PMID27841036-Compound-36

Drug Info

[28]

PMID27841036-Compound-38

Drug Info

[28]

PMID27841036-Compound-V

Drug Info

[28]

PMID27841036-Compound-XI

Drug Info

[28]

PMID27841036-Compound-XVII

Drug Info

[28]

Tetra/penta-cyclic pyridophthalazinone derivative 1

Drug Info

[28]

Drug Property Profile of Target

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(1) Molecular Weight (mw) based Drug Clustering

(2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering

(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering

(4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering

(5) Rotatable Bond Count (rotbonds) based Drug Clustering

(6) Topological Polar Surface Area (polararea) based Drug Clustering

"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five

Co-Targets

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Co-Targets

Co-Targets Info

Target Poor or Non Binders

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Target Poor or Non Binders

Target Poor or Non Binders Info

References

Top

REF 1

2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.

REF 2

URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7519).

REF 3

LYNPARZA approved by the US food and drug administration for the treatment of advanced ovarian cancer in patients with germline BRCA-mutations

REF 4

2016 FDA drug approvals. Nat Rev Drug Discov. 2017 Feb 2;16(2):73-76.

REF 5

2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.

REF 6

REF 7

ClinicalTrials.gov (NCT02163694) A Phase 3 Randomized, Placebo-controlled Trial of Carboplatin and Paclitaxel With or Without Veliparib (ABT-888) in HER2-negative Metastatic or Locally Advanced Unresectable BRCA-associated Breast Cancer. U.S. National Institutes of Health.

REF 8

Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)

REF 9

REF 10

Failure of iniparib to inhibit poly(ADP-Ribose) polymerase in vitro. Clin Cancer Res. 2012 Mar 15;18(6):1655-62.

REF 11

Therapeutic injection of PARP inhibitor INO-1001 preserves cardiac function in porcine myocardial ischemia and reperfusion without reducing infarct size. Shock. 2010 May;33(5):507-12.

REF 12

INO-1001 a novel poly(ADP-ribose) polymerase (PARP) inhibitor improves cardiac and pulmonary function after crystalloid cardioplegia and extracorporal circulation. Shock. 2004 May;21(5):426-32.

REF 13

ClinicalTrials.gov (NCT03602859) A Phase 3 Comparison of Platinum-based Therapy With TSR-042 and Niraparib Versus Standard of Care (SOC) Platinum-based Therapy as First-line Treatment of Stage III or IV Nonmucinous Epithelial Ovarian Cancer (FIRST). U.S. National Institutes of Health.

REF 14

ClinicalTrials.gov (NCT05417594) A Modular Phase I/IIa, Open-label, Multi-centre Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of Ascending Doses of AZD9574 as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Malignancies (CERTIS1). U.S.National Institutes of Health.

REF 15

ClinicalTrials.gov (NCT03933761) Pamiparib in Fusion Positive, Reversion Negative High Grade Serous Ovarian Cancer or Carcinosarcoma With BRCA1/2 Gene Mutations If Progression on Substrate Poly ADP Ribose Polymerase Inhibitbor (PARPI) or Chemotherapy (PRECISE). U.S. National Institutes of Health.

REF 16

BGP-15, a PARP-inhibitor, prevents imatinib-induced cardiotoxicity by activating Akt and suppressing JNK and p38 MAP kinases. Mol Cell Biochem. 2012 Jun;365(1-2):129-37.

REF 17

BGP-15 - a novel poly(ADP-ribose) polymerase inhibitor - protects against nephrotoxicity of cisplatin without compromising its antitumor activity. Biochem Pharmacol. 2002 Mar 15;63(6):1099-111.

REF 18

Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)

REF 19

ClinicalTrials.gov (NCT01605162) Phase 2 Study of the Poly(ADP-Ribose) Polymerase Inhibitor E7016 in Combination With Temozolomide in Subjects With Wild Type BRAF Stage IV or Unresectable Stage III Melanoma. U.S. National Institutes of Health.

REF 20

ClinicalTrials.gov (NCT01311713) Study to Determine the Maximum Tolerated Dose of the PARP Inhibitor CEP-9722 in Patients With Solid Tumors. U.S. National Institutes of Health.

REF 21

ClinicalTrials.gov (NCT01339650) Study of ABT-767 in Subjects With Breast Cancer 1 and Breast Cancer 2 (BRCA 1 and BRCA 2) Mutations and Solid Tumors or High Grade Serous Ovarian, Fallopian Tube, or Primary Peritoneal Cancer. U.S. National Institutes of Health.

REF 22

MP-124, a novel poly(ADP-ribose) polymerase-1 (PARP-1) inhibitor, ameliorates ischemic brain damage in a non-human primate model. Brain Res. 2011 Sep 2;1410:122-31.

REF 23

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800022742)

REF 24

Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.

REF 25

Clinical pipeline report, company report or official report of AstraZeneca

REF 26

Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)

REF 27

Company report (Mitsubishi Tanabe Pharma)

REF 28

PARP inhibitors as antitumor agents: a patent update (2013-2015).Expert Opin Ther Pat. 2017 Mar;27(3):363-382.

REF 29

Company report (ONO PHARMACEUTICAL)

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