NSC 617145 is targeted inhibitor of werner syndrome helicase (WRN) helicase, with an IC50 value of 230nM [1]. NSC 617145 can induce synthetic lethality via a genetic-based and/or chemically induced mechanism and render human cells deficient in the Fanconi Anemia (FA) pathway hypersensitive to the DNA cross-linking agent mitomycin C (MMC) in a WRN-dependent manner[2]. NSC 617145 has been widely used as an anti-cancer agent and has been applied in various cancer cell models to induce DNA damage[3].
In vitro, NSC 617145 treatment for 48 hours significantly inhibited the proliferation of PC3 cells, K562 cells, and HeLa cells, with IC50 values of 184.6 ± 36.3, 20.3 ± 11.5, and 237.0 ± 120.2nM, respectively[4]. Treatment with 250nM NSC 617145 for 4 days significantly reduced the number of LMY1 cells and induced cell apoptosis[5]. NSC 617145 treatment for 48 hours exhibited significant cytotoxicity in normal human liver LX2 cells and normal human renal epithelial HK2 cells, with the IC50 values of 1.81 ± 0.27μM and 5.64 ± 0.96μM, respectively[6].
References:
[1] Aggarwal M, Banerjee T, Sommers J A, et al. Werner syndrome helicase has a critical role in DNA damage responses in the absence of a functional fanconi anemia pathway[J]. Cancer research, 2013, 73(17): 5497-5507.
[2] Datta A, Brosh Jr R M. New insights into DNA helicases as druggable targets for cancer therapy[J]. Frontiers in molecular biosciences, 2018, 5: 59.
[3] Aggarwal M, Banerjee T, Sommers J A, et al. Targeting an Achilles’ heel of cancer with a WRN helicase inhibitor[J]. Cell cycle, 2013, 12(20): 3329-3335.
[4] Li H, Yu J, Yu G, et al. Design and synthesis of N-aryl-2-trifluoromethyl-quinazoline-4-amine derivatives as potential Werner-dependent antiproliferative agents[J]. Molecular Diversity, 2025, 29(1): 195-214.
[5] Moles R, Bai X T, Chaib-Mezrag H, et al. WRN-targeted therapy using inhibitors NSC 19630 and NSC 617145 induce apoptosis in HTLV-1-transformed adult T-cell leukemia cells[J]. Journal of hematology & oncology, 2016, 9(1): 121.
[6] Yu J, Yu G, Cheng S, et al. Quinazoline Derivative kzl052 Suppresses Prostate Cancer by Targeting WRN Helicase to Stabilize DNA Replication Forks[J]. International Journal of Molecular Sciences, 2025, 26(13): 6093.
NSC 617145是一种靶向Werner综合征解旋酶（WRN）的抑制剂，IC50值为230nM[1]。NSC 617145可通过基于遗传和/或化学诱导的机制诱发合成致死效应，并以WRN依赖性方式使范可尼贫血（FA）通路缺陷的人体细胞对DNA交联剂丝裂霉素C（MMC）超敏[2]。NSC 617145作为抗癌剂广泛应用于多种癌细胞模型，可诱导DNA损伤[3]。
在体外，NSC 617145处理48小时可显著抑制PC3、K562和HeLa细胞增殖，IC50值分别为184.6 ± 36.3nM、20.3 ± 11.5nM和237.0 ± 120.2nM[4]。250nM的NSC 617145处理LMY1细胞4天显著减少细胞数量并诱导凋亡[5]。NSC 617145处理正常人肝LX2细胞和肾上皮HK2细胞48小时表现出显著细胞毒性，IC50值分别为1.81 ± 0.27μM和5.64 ± 0.96μM [6]。