The nuclear enzyme poly(ADP-ribose) polymerase (PARP) plays an important role in the repair of DNA strand breaks, including those induced by radiation, thus making it a potential target for radiosensitizers. INO-1001 is a novel and potent inhibitor of PARP. INO-1001 at a concentration of 0.05 μM resulted in approximately 50% inhibition of PARP activity in CHO cells after 30 minutes treatment. And concentrations of 1 μM or greater resulted in more than 95% inhibition of the enzyme. Exponentially growing CHO cells were treated with 10 μM INO-1001 starting 30 min. prior to irradiation. INO-1001 significantly sensitized CHO cells to radiation. The initial slope of the survival curve for drug treated and irradiated cultures was greater than radiation alone. The enhancement ratio (ER) at 10% survival was 1.6. A similar radiosensitizing effect was observed in a murine tumor cell line with an ER of 1.7. The fibroblasts were also sensitized by the drug treatment with an ER of 1.4[2]. Immediately after CCI (controlled cortical impact) or sham-injury mice received either INO-1001 (1.6 mg/kg) or vehicle via intracerebral injection (5 microl over 5 min) in a randomized fashion. Local treatment with INO-1001 preserved brain NAD+ levels 2 h after CCI. In the Morris water maze, treatment with INO-1001 reduced the latency to find the hidden platform and increased the time spent in the target quadrant versus vehicle after CCI[3].
Induced centrosome amplification and chromosomal aneuploidy
Int J Mol Sci. 2023 Dec 27;25(1):383.
H9C2 cells
20 µM
12 hours
Inhibited DOX-induced PARylation, reduced cardiomyocyte apoptosis and mitochondrial damage
Acta Pharm Sin B. 2019 Jul;9(4):782-793.
Human intestinal organoids
20 mM
12 hours
Inhibited PARP1-dependent parthanatos and reduced cell death
Cell Death Discov. 2024 Jul 31;10(1):345.
HeLa cells
10 mM
20 hours
To investigate the effect of 3-aminobenzamide on cell surface peptidase activity in UVB-induced apoptotic HeLa cells. Results showed that 3AB treatment significantly reduced cell surface peptidase activity in apoptotic cells.
Int J Mol Sci. 2012;13(3):2650-2675.
Neonatal rat cardiomyocytes
500 µM
24 hours
Inhibition of PARP-1 activity, attenuating isoprenaline-induced cardiomyocyte hypertrophy
Br J Pharmacol. 2015 Jun;172(11):2852-63.
Rice seedlings
1 mM
24 hours
3-Aminobenzamide, as a PARP inhibitor, enhanced cold tolerance in rice seedlings by reducing NAD+ consumption and maintaining energy homeostasis.
Antioxidants (Basel). 2022 Dec 29;12(1):79.
Caco-2 cells
20 mM
6 hours
Inhibited PARP1-dependent parthanatos and reduced cell death
Cell Death Discov. 2024 Jul 31;10(1):345.
Immortalized MEF
7 mM
72 hours
Induced centrosome amplification but did not cause chromosomal aneuploidy
Int J Mol Sci. 2023 Dec 27;25(1):383.
U-937 cells
5 µM
8 hours
Evaluate the antileukemic potential of MAC681 in U-937 cells, showing induction of DNA damage and necroptotic-like cell death.
Biomark Res. 2024 May 4;12(1):47.
K-562 cells
5 µM
8 hours
Evaluate the antileukemic potential of MAC681 in K-562 cells, showing induction of DNA damage, mitochondrial dysfunction, and necroptotic-like cell death.
Biomark Res. 2024 May 4;12(1):47.
Rd2 organotypic retinal cultures
10 nM
one week
Significantly reduced PARylation levels and photoreceptor cell death
Acta Neuropathol Commun. 2025 Apr 1;13(1):68.
3-Aminobenzamide 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Rice
Rice seedlings
Foliar spray
1 mM
Single treatment, 24 hours of cold stress
The combination of 3-aminobenzamide and OPCs significantly enhanced cold tolerance in rice seedlings by inhibiting PARP activity and enhancing ATPase activity to maintain energy homeostasis.
Antioxidants (Basel). 2022 Dec 29;12(1):79.
Rats
Haemorrhagic shock model
Intravenous injection
10 mg/kg
Single dose 5 min prior to resuscitation
To evaluate the effects of 3-aminobenzamide on organ injury and dysfunction caused by haemorrhagic shock. Results showed that 3-aminobenzamide attenuated renal dysfunction, hepatocellular injury, and pancreatic injury.
To evaluate the protective effect of 3-Aminobenzamide on light-induced retinal damage. Results showed that 3-Aminobenzamide significantly alleviated light-induced structural and functional damage to the retina.
Cell Commun Signal. 2020 Feb 17;18(1):27
SD rats
Abdominal aortic constriction (AAC) surgery-induced cardiac hypertrophy model
Intraperitoneal injection
20 mg/kg
Once daily for 6 weeks
Pre-treatment with 3AB alleviated AAC-induced translocation of nuclear HMGB1 protein, cardiac hypertrophy, and heart dysfunction
Acta Pharmacol Sin. 2019 May;40(5):589-598
Mice
Necrotizing enterocolitis model
Intraperitoneal injection
20 μg/g
4 consecutive days
Inhibited parthanatos and alleviated intestinal epithelial damage and inflammatory response
Cell Death Discov. 2024 Jul 31;10(1):345.
Sprague-Dawley rats
DOX-induced cardiomyopathy model
Intraperitoneal injection
40 mg/kg/day
Once daily for 7 days
Alleviated DOX-induced cardiac apoptosis, mitochondrial dysfunction and heart dysfunction
Acta Pharm Sin B. 2019 Jul;9(4):782-793.
C57BL/6 mice
C1498 cell xenograft model
Subcutaneous injection
5 µM
Single injection, observed for one week
Evaluate the immunogenic potential of MAC681 in vivo, showing that MAC681-treated cells could generate an immunogenic vaccine and significantly reduce tumor growth.
Biomark Res. 2024 May 4;12(1):47.
Female rats
Takotsubo syndrome model
Intraperitoneal injection
50 mg/kg
Single dose, lasting 24 hours
Pretreatment with 3-aminobenzamide (a PARP-1 inhibitor) attenuates negative inotropic changes
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