PJ34 is an effective and specific PARP inhibitor with an IC50 value of 110nM [1]. PJ34 promotes cell death by inhibiting PARP1-mediated DNA repair, and leads to a decrease in NF-κB expression and specifically blocks the mitosis of cancer cells[2]. PJ34 has been widely used to kill tumor cells and has been employed in the development of novel combined therapies to efficiently enhance the cytotoxicity of chemotherapy drugs[3].
In vitro, PJ34 treatment for 48 hours significantly inhibited the viability of OVCAR-3 cells and SKOV-3 cells, with the IC50 values being 18.7µM and 28.5µM, respectively[4]. Treatment with 50µM PJ34 for 72 hours induced cell cycle arrest and apoptosis in HTLV-I-transformed MT-2 cells[5]. Treatment with 10µM PJ34 for 24 hours resulted in mitotic defects in M14 cells and promoted abnormal accumulation of actin in the nucleolus[6].
In vivo, PJ34 treatment via intraperitoneal injection at a dose of 10mg/kg three times weekly for 4 weeks alleviated the accumulation of triglycerides (TG) in the liver of alcohol-fed mice and reduced the hepatic gene expression of sterol regulatory element-binding protein 1c, DGAT1, and DGAT2[7]. Intraperitoneal injection of PJ34 (50μg) at 2 hours before and 6 hours after middle cerebral artery occlusion (MCAo) significantly reduced the cerebral infarct volume in SV/129 mice [8].
References:
[1] Iwashita A, Tojo N, Matsuura S, et al. A novel and potent poly (ADP-ribose) polymerase-1 inhibitor, FR247304 (5-chloro-2-[3-(4-phenyl-3, 6-dihydro-1 (2 H)-pyridinyl) propyl]-4 (3 H)-quinazolinone), attenuates neuronal damage in in vitro and in vivo models of cerebral ischemia[J]. The Journal of pharmacology and experimental therapeutics, 2004, 310(2): 425-436.
[2] Cohen-Armon M. The modified phenanthridine PJ34 unveils an exclusive cell-death mechanism in human cancer cells[J]. Cancers, 2020, 12(6): 1628.
[3] Mann M, Chauhan S S, Kumar S, et al. PJ34-mediated PARP-1 enzymatic activity inhibition in cervical cancer modulates the cellular response to cisplatin[J]. Cancer Research, 2016, 76(14_Supplement): 2152-2152.
[4] Güler A E, Tuncer M C, Özdemir İ. Synergistic Antitumor Activity of Curcumin and the PARP1 Inhibitor PJ34 in Platinum-Sensitive and Resistant Ovarian Cancer Cells[J]. Cancers, 2026, 18(4): 620.
[5] Bai X T, Moles R, Chaib-Mezrag H, et al. Small PARP inhibitor PJ-34 induces cell cycle arrest and apoptosis of adult T-cell leukemia cells[J]. Journal of hematology & oncology, 2015, 8(1): 117.
[6] Chevanne M, Zampieri M, Caldini R, et al. Inhibition of PARP activity by PJ‐34 leads to growth impairment and cell death associated with aberrant mitotic pattern and nucleolar actin accumulation in M14 melanoma cell line[J]. Journal of cellular physiology, 2010, 222(2): 401-410.
[7] Huang S, Zhang B, Chen Y, et al. Poly (ADP-ribose) polymerase inhibitor PJ34 attenuated hepatic triglyceride accumulation in alcoholic fatty liver disease in mice[J]. The Journal of pharmacology and experimental therapeutics, 2018, 364(3): 452-461.
[8] Abdelkarim G E, Gertz K, Harms C, et al. Protective effects of PJ34, a novel, potent inhibitor of poly (ADP-ribose) polymerase (PARP) in in vitro and in vivo models of stroke[J]. International journal of molecular medicine, 2001, 7(3): 255-260.
PJ34是一种有效且特异性的PARP抑制剂，IC50值为110nM[1]。PJ34通过抑制PARP1介导的DNA修复来促进细胞死亡，导致NF-κB表达降低，并能特异性地阻断癌细胞的有丝分裂[2]。PJ34已被广泛用于杀灭肿瘤细胞，并已被用于开发新型联合疗法，以有效增强化疗药物的细胞毒性[3]。
在体外，PJ34处理OVCAR-3细胞和SKOV-3细胞48小时，显著抑制了细胞活力，IC50值分别为18.7µM和28.5µM[4]。50µM的PJ34处理HTLV-I转化的MT-2细胞72小时，诱导了细胞周期阻滞和凋亡[5]。10µM的PJ34处理M14细胞24小时，导致有丝分裂缺陷，并促进了肌动蛋白在核仁中的异常积累[6]。
在体内，每周腹腔注射3次10mg/kg剂量的PJ34，持续4周，减轻了酒精喂养小鼠肝脏中的甘油三酯（TG）积累，并降低了肝脏中sterol regulatory element-binding protein 1c、DGAT1和DGAT2的基因表达[7]。在脑中动脉闭塞前2小时和后6小时分别腹腔注射50µg的PJ34，显著减少了SV/129小鼠的脑梗死体积[7]。