PARP1, also called as Poly (ADP-ribose) polymerase, is involved in the signaling of DNA damage. It can recognize and bind DNA single or double-strand breaks, thus possessing various cellular function, including regulation of apoptosis and chromosome stability, gene amplification and transcription, as well as cell division and differentiation. Rucaparib Phosphate is a potent PARP inhibitor with Ki value of 1.4 nM (measured by enzyme assays)[1]. Rucaparib Phosphate at dose ranging in 1-10 μM can suppress the level of PAR, as well as induce γ-H2AX, formation and PARP cleavage in a dose-dependent manner indicative of DNA damage and apoptosis, respectively, in MDA-MB468, MDA-MB-231, and Cal-51 cells in the presence of 5% FBS-supplemented DMEM medium for 72 h. Rucaparib Phosphate at concentrations >2.5 μM decreased the p-Stat3 in MDA-MB-468 and MDA-MB-231, as well as dose-dependently increased the p-Akt-S473 in MDA-MB-468 and Cal-51 cells[2]. Rucaparib Phosphate can chemosensitize neuroblastoma cell lines to temozolomide or topotecan in vitro and in vivo. Rucaparib Phosphate at concentration of 0.4 μM caused a significant sensitization of topotecan (1-30 nM) and temozolomide (1-200 μM) in NB-1691, SH-SY-5Y and SKNBE(2c) cells. Rucaparib Phosphate (1 mg/kg) increased the temozolomide-induced (68 mg/kg) tumor growth delay by 50% (to >89 days) and complete and increased the number of mice with complete and persistent tumor regressions (≥ 100 days). Co-administration of Rucaparib Phosphate (1 mg/kg) with topotecan (1 mg/kg) increased total number of complete regressions[3].
作用机制
Rucaparib Phosphate can compete with NAD+ for the PARP catalytic site[4]
Rucaparib phosphate/瑞卡帕布磷酸盐 细胞实验
Cell Line
Concentration
Treated Time
Description
References
GBM12 cells
1 µM and 3 µM
14 days
To evaluate the efficacy of Rucaparib in combination with TMZ, results showed that Rucaparib significantly enhanced the efficacy of TMZ.
Mol Cancer Ther. 2015 Dec;14(12):2735-43.
MDCKII cells
2 µM
60 min
To evaluate the accumulation of Rucaparib in MDCKII cells, results showed that Rucaparib is a substrate for both MDR1 and BCRP1 efflux pumps.
Mol Cancer Ther. 2015 Dec;14(12):2735-43.
MEFs
100 nM
2 weeks
To evaluate the sensitivity of MEFs to Rucaparib, results showed that Brca1CC/Δ11 cells formed more colonies in the presence of 100 nM Rucaparib, but significantly fewer colonies at 1000 nM Rucaparib.
Mol Cell. 2020 Jun 4;78(5):951-959.e6.
T47D
1 μM
24 h
To detect the effect of Rucaparib on DNA damage, the results showed that Rucaparib induced more DNA damage.
Cell Death Dis. 2024 Dec 18;15(12):898.
MDA-MB-231
1 μM
24 h
To detect the effect of Rucaparib on NAD⁺ levels, the results showed that Rucaparib effectively prevented NAD⁺ depletion
Cell Death Dis. 2024 Dec 18;15(12):898.
CD4+ T cells
10 µM
12 h
Inhibition of PARP enzyme activity, reducing IL-17 release and ROS levels
Cell Rep Med. 2023 Sep 19;4(9):101157.
GEA PDX-derived primary cells
1.25 –40μM
6 days
To evaluate the growth inhibitory effect of Rucaparib on GEA PDX-derived primary cells, results showed that cells with BRCA2 mutations were sensitive to Rucaparib
Cancer Res. 2023 May 15;83(10):1699-1710.
MDA-MB-231 cells
15 µM
4, 8, 24 h
To study the effect of Rucaparib on the transcriptomic dynamics of MDA-MB-231 cells, revealing transcriptomic changes at different time points.
Mol Syst Biol. 2021 Apr;17(4):e10060.
IB114
1.488 μM
72 h
To study the antiproliferative activity of Rucaparib on IB114 cells, IC50 value was 1.488 μM
J Hematol Oncol. 2017 Apr 11;10(1):84.
IB115
1.104 μM
72 h
To study the antiproliferative activity of Rucaparib on IB115 cells, IC50 value was 1.104 μM
J Hematol Oncol. 2017 Apr 11;10(1):84.
IB111
1.364 μM
72 h
To study the antiproliferative activity of Rucaparib on IB111 cells, IC50 value was 1.364 μM
J Hematol Oncol. 2017 Apr 11;10(1):84.
IB133
58.08 μM
72 h
To study the antiproliferative activity of Rucaparib on IB133 cells, IC50 value was 58.08 μM
J Hematol Oncol. 2017 Apr 11;10(1):84.
IB134
40.88 μM
72 h
To study the antiproliferative activity of Rucaparib on IB134 cells, IC50 value was 40.88 μM
J Hematol Oncol. 2017 Apr 11;10(1):84.
IB136
31.35 μM
72 h
To study the antiproliferative activity of Rucaparib on IB136 cells, IC50 value was 31.35 μM
J Hematol Oncol. 2017 Apr 11;10(1):84.
IB112
29.5 μM
72 h
To study the antiproliferative activity of Rucaparib on IB112 cells, IC50 value was 29.5 μM
J Hematol Oncol. 2017 Apr 11;10(1):84.
IB128
12.036 μM
72 h
To study the antiproliferative activity of Rucaparib on IB128 cells, IC50 value was 12.036 μM
J Hematol Oncol. 2017 Apr 11;10(1):84.
93T449
19.2 μM
72 h
To study the antiproliferative activity of Rucaparib on 93T449 cells, IC50 value was 19.2 μM
J Hematol Oncol. 2017 Apr 11;10(1):84.
GBM U251 cells
0.2, 0.5, 1, 2, 5, 10, 25, 50, 100 μM
96 h
To evaluate the antiproliferative effect of Rucaparib on GBM U251 cells, results showed that Rucaparib inhibited cell proliferation in a dose-dependent manner with an IC50 value of 14.36 μM.
Cell Death Dis. 2021 May 26;12(6):546.
GBM U87MG cells
0.2, 0.5, 1, 2, 5, 10, 25, 50, 100 μM
96 h
To evaluate the antiproliferative effect of Rucaparib on GBM U87MG cells, results showed that Rucaparib inhibited cell proliferation in a dose-dependent manner with an IC50 value of 15.00 μM.
Cell Death Dis. 2021 May 26;12(6):546.
Rucaparib phosphate/瑞卡帕布磷酸盐 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
GBM12 flank xenograft model
Intraperitoneal injection
1 mg/kg
Every 28 days × 3 cycles, daily for 5 days
To evaluate the efficacy of Rucaparib in combination with TMZ in the GBM12 flank xenograft model, results showed that Rucaparib significantly prolonged the time to tumor regrowth.
Mol Cancer Ther. 2015 Dec;14(12):2735-43.
Mice
Brca1CC/Δ11 mice
Oral
200 mg/kg
Twice daily for 5 days
To evaluate the tolerability of Rucaparib in Brca1CC/Δ11 mice, results showed that Rucaparib treatment led to a reduction in blood lymphocytes, but was unaffected and mice survived.
Mol Cell. 2020 Jun 4;78(5):951-959.e6.
Mouse
BRCA1-deficient mouse ovarian tumor cell line BR5
Oral
150 mg/kg
Twice daily for 5 days, 2 days off, then 5 days
To evaluate the sensitivity of BRCA1-deficient tumors to PARPi, results showed that BRCA1-deficient tumors were sensitive to PARPi and exhibited replication tract lengthening after treatment
Mol Cell. 2021 Aug 5;81(15):3128-3144.e7.
NSG mice
MOLT4 tumor xenograft model
Intraperitoneal injection
40 mg/kg
Twice daily for 16 days
To evaluate the anti-tumor efficacy of 180055 in BRCA1-mutated tumor models, the results showed that 180055 significantly inhibited tumor growth with fewer side effects.
Cell Death Dis. 2024 Dec 18;15(12):898.
Mice
IB115 cell xenograft model
Intraperitoneal injection
10 mg/kg
Five times per week for 3 weeks
To evaluate the antitumor effect of Rucaparib on the IB115 cell xenograft model, the results showed that Rucaparib significantly prolonged progression-free survival
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