Itareparib (NMS-03305293; NMS-293) is a selective, orally active, blood-brain barrier-permeable PARP1 inhibitor with an IC50 < 0.01 μM. Itareparib does not form PARP1-DNA trapping complexes, avoids PARP-DNA "retention", reduces PAR levels and inhibits the growth of homologous recombination-deficient cells. Itareparib can be used in research on advanced solid tumors, recurrent gliomas and other conditions [1] [2].
In Vivo, Itareparib is active in breast cancer cells with BRCA mutations and in xenograft animal models derived from these cells[2].
In Vitro, Itareparib can selectively inhibit the growth of HR-deficient cells in vitro and reduce the PAR level of the cells[1]. Itareparib does not cause damage to normal myeloid cells, indicating that it has a lower risk of hematological toxicity compared to non-selective PARP inhibitors[2]. Itareparib shows effective anti-proliferative activity in breast cancer cell lines with BRCA mutations[2].
References:
[1]. Li Q, et al. A new wave of innovations within the DNA damage response. Signal transduction and targeted therapy. 2023 Sep 08;8(1):338.
[2]. Ray A, et al. Targeting PARP1: A Promising Approach for Next-Generation Poly (ADP-ribose) Polymerase Inhibitors. Current breast cancer reports. 2025;17(1):22.
In Vivo, Itareparib is active in breast cancer cells with BRCA mutations and in xenograft animal models derived from these cells[2].
In Vitro, Itareparib can selectively inhibit the growth of HR-deficient cells in vitro and reduce the PAR level of the cells[1]. Itareparib does not cause damage to normal myeloid cells, indicating that it has a lower risk of hematological toxicity compared to non-selective PARP inhibitors[2]. Itareparib shows effective anti-proliferative activity in breast cancer cell lines with BRCA mutations[2].
References:
[1]. Li Q, et al. A new wave of innovations within the DNA damage response. Signal transduction and targeted therapy. 2023 Sep 08;8(1):338.
[2]. Ray A, et al. Targeting PARP1: A Promising Approach for Next-Generation Poly (ADP-ribose) Polymerase Inhibitors. Current breast cancer reports. 2025;17(1):22.