ZEJULA Inhibits PARP1 and PARP2, Leading to Cancer Cell Death in Pre-Clinical Studies1

In Preclinical Studies, ZEJULA-Induced Cytotoxicity Was Observed in Tumor Cell Lines With or Without Deficiencies in BRCA1/21

ZEJULA is an inhibitor of poly(ADP-ribose) polymerase (PARP) enzymes, PARP1 and PARP2, which play a role in DNA repair.1 In vitro studies suggest that ZEJULA’s cytotoxic effects may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complexes resulting in DNA damage, apoptosis, and cell death.1

BRCA1/2, breast cancer susceptibility genes 1 and 2.

Preclinical studies suggest the activity of PARP inhibitors depends on tumor exposure and subsequent PARP1/2 inhibition.5

  • Tumor cells carrying a BRCA mutation have been shown to be significantly more sensitive to PARP inhibition than tumors that do not carry a BRCA mutation6
  • It is hypothesized that in tumors without a BRCA mutation, PARP inhibitors may need to achieve higher tumor concentrations for effect6

All currently approved PARP inhibitors have distinct pharmacologic profiles

  • Due to the clear differences that exist in clinical pharmacology and chemical properties among the PARP inhibitors (as shown by pre-clinical data), each PARP inhibitor needs to be assessed based on its own data; data cannot be extrapolated from one PARP inhibitor to another
  • When choosing a PARP inhibitor, it is important to understand pharmacologic properties and data in the specific population under consideration

Pharmacologic properties are not meant to suggest clinical efficacy.

BRCA, breast cancer susceptibility gene; CEs, carboxylesterases; PARP, poly(ADP-ribose) polymerase; Vd/F, apparent volume of distribution.

The Distinct Pharmacology of ZEJULA

Watch the following videos to learn more about the therapeutic rationale behind PARP inhibition and aspects of how ZEJULA behaves in the body

1: Volume of Distribution 0:14
2: Bioavailability 0:21
3: Intro to PARP Inhibition 2:17
4: Permeability 0:39
5: Important Safety Information 0:43
6: Conclusion 0:57
7: Selectivity 0:24
8: Half-Life 0:15

References: 1. ZEJULA (niraparib) [package insert]. Waltham, MA: TESARO, Inc.; October 2019. 2. Satoh MS, Lindahl T. Role of poly(ADP-ribose) formation in DNA repair. Nature. 1992;356(6367):356-358. 3. Rein ID, Landsverk KS, Micci F, Patzke S, Stokke T. Replication-induced DNA damage after PARP inhibition causes G2 delay, and cell line-dependent apoptosis, necrosis and multinucleation. Cell Cycle. 2015;14(20):3248-3260. 4. Data on file. TESARO, Inc. 5. Ricks TK, Chiu HJ, Ison G, et al. Successes and challenges of PARP inhibitors in cancer therapy. Front Oncol. 2015;5:222. doi: 10.3389/fonc.2015.00222. 6. Farmer H,  McCabe N, Lord CJ, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005;434(7035):917-921. 7. Lynparza (olaparib) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; July 2019. 8. Rubraca (rucaparib) [package insert]. Boulder, CO: Clovis Oncology, Inc; April 2018.

Efficacy data


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Study design


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