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PARP inhibition

CompoundSaruparib

Area under investigation

Advanced solid tumors, HR-positive/HER2-negative breast cancer, Localized prostate cancer, mCRPC, mHSPC, Ovarian cancer, Pancreatic cancer, TNBC, NSCLC, SCLC, BRCAm or PALB2m breast cancer

Scientific PillarDNA Damage Response

Target Overview

Poly [ADP-ribose] polymerases (PARPs) are a group of proteins known to be involved in the repair of single-strand breaks in DNA.1

A healthy cell’s DNA undergoes damage every day, with approximately 10,000 spontaneous single-strand breaks that require repair.1

Inhibition of PARP1 with AZD5305 leads to the trapping of PARP bound to DNA single-strand breaks, stalling of replication forks, their collapse and the generation of DNA double-strand breaks. In tumor cells that already have compromised DNA repair mechanisms (such as loss of BRCA1 or BRCA2 function, affecting double-strand break repair), inhibition of PARP leads to excessive accumulation of DNA damage and may cause death of the cell.1,2

Compound Overview

Saruparib (AZD5305) is an investigational, new generation PARP inhibitor. It is designed to selectively inhibit and trap PARP1, enabling efficacy, while broadening the opportunity for clinical benefit by allowing combination approaches with different treatment options.3,4

Mechanism of Action

  • Mechanism of Action
  • Mechanism of Action

References

1. Underhill C, Toulmonde M, Bonnefoi H. Ann Oncol. 2011;22(2):268-279. 2. Yelamos J, Farres J, Llacuna L, et al. Am J Cancer Res. 2011;1(3):328-346. 3. Farrés J, Martín-Caballero J, Martínez C, et al. Blood. 2013;122(1):44-54. 4. Farrés J, Llacuna L, Martín-Caballero J, et al. Cell Death Differ. 2015;22(7):1144-1157.

Clinical trial information


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Abbreviations

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  • ADP

    adenosine diphosphate

  • ADT

    androgen-deprivation therapy

  • AE

    adverse event

  • AML

    acute myeloid leukemia

  • ARPI

    androgen receptor pathway inhibitor

  • BRCA

    breast cancer susceptibility gene

  • ECOG PS

    Eastern Cooperative Oncology Group Performance Score

  • HRQoL

    health-related quality of life

  • HRRm

    homologous recombination repair gene mutation

  • MDS

    myelodysplastic syndrome

  • mHSPC

    metastatic hormone-sensitive prostate cancer

  • PARP

    poly (ADP-ribose) polymerase

  • pcARPI

    physician’s choice of androgen receptor pathway inhibitor

  • PCWG-3

    Prostate Cancer Clinical Trials Working Group 3

  • PFS2

    time to second progression or death

  • PRO

    patient-reported outcomes

  • PSA

    prostate-specific antigen

  • SAE

    serious adverse event

  • SSE-FS

    symptomatic skeletal event-free survival

  • TEAE

    treatment emergent adverse event

  • TFST

    time to first subsequent therapy

  • TTCR

    time to the first castration-resistant event

  • TTDF

    time to deterioration in fatigue

  • TTDPF

    time to deterioration in physical function

  • TTDUS

    time to deterioration in urinary symptoms

  • TTPP

    time to pain progression

Some compounds herein refer to selected AstraZeneca pipeline products still under development. AstraZeneca pipeline products are investigational products and, as such, are not approved by the US Food & Drug Administration (FDA), the European Medicines Agency (EMA) or any other regulatory agency for the uses under investigation. Information regarding these investigational products should, under no circumstances, be regarded as a recommendation for their use or of their safety or efficacy.

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Veeva ID: Z4-80919 US-109129 DE-92568 Last Updated April 20263/26
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