BIBR 1532 is a potent small molecule inhibitor of human telomerase, with an IC50 value of 5µM for telomerase inhibition. BIBR 1532 causes telomeres to shorten and reduces tumor cell proliferation[1].
In vitro, BIBR 1532 (30µM; 48h) increases arsenic trioxide-mediated apoptosis in acute promyelocytic leukemia cells[2]. BIBR 1532 (20μM or 40μM; 72h) combined with radiotherapy induces ferroptosis in NSCLC cells and activates cGAS-STING pathway to promote anti-tumor immunity[3].
In vivo, BIBR 1532 (166-1326pg/μl; twice; intravitreal injection) specifically induces the suppression of choroidal neovascularization (CNV) in mice through the inhibition of telomerase[4]. In a mouse xenograft model, BIBR 1532 (1.5mg/kg; 3 days; i.p.) treatment synergized with ionizing radiation (IR) at nontoxic dose levels promoted the antitumor efficacy of IR without toxicity to hematologic and internal organs[5].
References:
[1] Barma DK, Elayadi A, Falck JR, et al. Inhibition of telomerase by BIBR 1532 and related analogues. Bioorg Med Chem Lett. 2003 Apr 7;13(7):1333-6.
[2] Bashash D, Ghaffari SH, Zaker F, et al. BIBR 1532 increases arsenic trioxide-mediated apoptosis in acute promyelocytic leukemia cells: therapeutic potential for APL. Anticancer Agents Med Chem. 2013 Sep;13(7):1115-25.
[3] Bao Y, Pan Z, Zhao L, et al. BIBR1532 combined with radiotherapy induces ferroptosis in NSCLC cells and activates cGAS-STING pathway to promote anti-tumor immunity. J Transl Med. 2024 May 30;22(1):519.
[4] Kumar A, Nagasaka Y, Jayananthan V, et al. Therapeutic targeting of telomerase ameliorates experimental choroidal neovascularization. Biochim Biophys Acta Mol Basis Dis. 2024 Jun;1870(5):167156.
[5] Ding X, Cheng J, Pang Q, et al. BIBR1532, a Selective Telomerase Inhibitor, Enhances Radiosensitivity of Non-Small Cell Lung Cancer Through Increasing Telomere Dysfunction and ATM/CHK1 Inhibition. Int J Radiat Oncol Biol Phys. 2019 Nov 15;105(4):861-874.
BIBR 1532是一种强效的小分子人类端粒酶抑制剂，对端粒酶的抑制作用的IC50值为5μM。BIBR 1532会导致端粒缩短并减少肿瘤细胞的增殖[1]。
在体外实验中，BIBR 1532（30µM; 48h）增加了急性早幼粒细胞白血病细胞中三氧化二砷介导的凋亡[2]。BIBR 1532（20µM或40µM; 72h）与放疗联合使用可在非小细胞肺癌（NSCLC）细胞中诱导铁死亡，并激活cGAS-STING通路以促进抗肿瘤免疫[3]。
在体内实验中，BIBR 1532（166-1326pg/µl; 两次; 眼内注射）通过抑制端粒酶特异性地诱导小鼠脉络膜新生血管（CNV）的抑制[4]。在小鼠异种移植模型中，非毒性剂量水平的BIBR 1532（1.5mg/kg; 3天; 腹腔注射）治疗与电离辐射（IR）协同作用，增强了IR的抗肿瘤效果，且对造血系统和内脏器官无毒性[5]。