Pamiparib (BGB-290) is a potent and oral Poly (ADP-ribose) polymerase (PARP) inhibitor, with IC50 values of 1.3nM and 0.9nM for PARP-1 and PARP-2, respectively [1]. Pamiparib has excellent bioavailability and exhibits high cytotoxicity and potent DNA-trapping activity (with an IC50 of 13nM)[2]. Pamiparib has been widely used as an anti-cancer agent in both cancer cells and xenograft (PDX) models[3].
In vitro, Pamiparib treatment for 7 days significantly inhibited MDA-MB-436 cells and UWB1.289 cells, with IC50 values of 41±15nM and 54nM, respectively[4]. Treatment of OCI-Ly3 cells with 25µM Pamiparib for 24 hours promoted doxorubicin-induced cell apoptosis and reversed the chemoresistance associated with miRNA-363-3p[5]. The 10μM dose of Pamiparib treatment for 14 days significantly inhibited the colony formation of Fh1-deficient RENCA cells[6].
In, vivo, Pamiparib treatment via oral administration at 3mg/kg twice daily for 3 weeks significantly inhibited tumor growth in mice with SW1990 cell xenografts and reduced the number of Ki-67-positive tumor cells[7]. A single oral administration of 3mg/kg Pamiparib for 4 hours inhibited PARylation in the brain and tumor tissues of the intracranial H209 cell xenograft tumor mouse model, and the survival period of the mice was significantly prolonged[8].
References:
[1] Wang H, Ren B, Liu Y, et al. Discovery of pamiparib (BGB-290), a potent and selective poly (ADP-ribose) polymerase (PARP) inhibitor in clinical development[J]. Journal of Medicinal Chemistry, 2020, 63(24): 15541-15563.
[2] Tang Z, Liu Y, Zhen Q, et al. BGB-290: A highly potent and specific PARP1/2 inhibitor potentiates anti-tumor activity of chemotherapeutics in patient biopsy derived SCLC models[J]. Cancer Research, 2015, 75(15_Supplement): 1653-1653.
[3] Gupta S K, Mladek A C, Jain S, et al. Pamiparib-induced replication stress augments the efficacy of temozolomide in GBM PDX models[J]. Cancer Research, 2025, 85(8_Supplement_1): 2910-2910.
[4] Xiong Y, Guo Y, Liu Y, et al. Pamiparib is a potent and selective PARP inhibitor with unique potential for the treatment of brain tumor[J]. Neoplasia, 2020, 22(9): 431-440.
[5] Zhou W, Xu Y, Zhang J, et al. MiRNA-363-3p/DUSP10/JNK axis mediates chemoresistance by enhancing DNA damage repair in diffuse large B-cell lymphoma[J]. Leukemia, 2022, 36(7): 1861-1869.
[6] Ueno D, Vasquez J C, Sule A, et al. Targeting Krebs-cycle-deficient renal cell carcinoma with Poly ADP-ribose polymerase inhibitors and low-dose alkylating chemotherapy[J]. Oncotarget, 2022, 13: 1054.
[7] Wang Y, Zheng K, Xiong H, et al. PARP inhibitor upregulates PD-L1 expression and provides a new combination therapy in pancreatic cancer[J]. Frontiers in immunology, 2021, 12: 762989.
[8] Tang Z, Jiang B, Shi Z, et al. BGB-290, a novel PARP inhibitor with unique brain penetration ability, demonstrated strong synergism with temozolomide in subcutaneous and intracranial xenograft models[J]. Cancer Research, 2015, 75(15_Supplement): 1651-1651.
Pamiparib (BGB-290)是一种强效口服的聚腺苷二磷酸核糖聚合酶（PARP）抑制剂，对PARP-1和PARP-2的IC50值分别为1.3nM和0.9nM[1]。Pamiparib具有优异的生物利用度，表现出高细胞毒性和强效DNA捕获活性（IC50=13nM）[2]。Pamiparib已广泛应用于癌细胞和异种移植（PDX）模型的抗癌研究[3]。
在体外，Pamiparib处理7天可显著抑制MDA-MB-436和UWB1.289细胞，IC50值分别为41±15nM和54nM[4]。25µM的Pamiparib处理OCI-Ly3细胞24小时能促进多柔比星诱导的细胞凋亡，并逆转与miRNA-363-3p相关的化疗耐药性[5]。10µM的Pamiparib处理Fh1缺陷型RENCA细胞14天可显著抑制克隆细胞形成[6]。
在体内，SW1990细胞异种移植小鼠每日两次口服Pamiparib（3mg/kg；持续3周）可显著抑制肿瘤生长并减少Ki-67阳性肿瘤细胞数量[7]。颅内H209细胞异种移植瘤小鼠单次口服3mg/kg剂量的Pamiparib（4小时）能抑制脑组织和肿瘤中的PAR化修饰，并显著延长生存期[8]。