PROTAC-O4I2 is a 2-aminothiazole derivative that selectively degrades SF3B1 and induces apoptosis in a CRBN-dependent manner (IC50 = 0.244μM) [1]. PROTAC-O4I2 is commonly used to treat cancer [2].
In K562 cells, PROTAC-O4I2 (1µM; 48h) induces apoptosis in K562 WT cells [1]. In K562 overexpressing SF3B1WT, there is an inversion of the cytotoxicity profiles, making PROTAC-O4I2 (1µM; 72h) twice as effective as Pladienolide B against cell viability [3].
In tumor bearing flies models, administration of PROTAC-O4I2 (10μM; po; 30d) significantly reduced stem cell activity and tumor growth in the intestine of CRISPR/Cas9-mediated Notch knockout (Notch-gRNA2x) animals [1].
References:
[1]. Gama-Brambila RA, Chen J, Zhou J, et al. A PROTAC targets splicing factor 3B1. Cell chemical biology. 2021 Nov 18; 28(11): 1616-1627.
[2]. Chen Y, Yang Q, Xu J, et al. PROTACs in gastrointestinal cancers. Molecular Therapy-Oncolytics. 2022 Dec 15; 27: 204-223.
[3]. Gama Brambila RA. Biological Assessment and Tests of Activity of Two Novel Proteolysis Targeting Chimeras (PROTACs) (Doctoral dissertation).
PROTAC-O4I2是一种2-氨基噻唑衍生物，能够选择性降解SF3B1并以CRBN依赖的方式诱导细胞凋亡（IC50 = 0.244μM） [1]。PROTAC-O4I2常用于治疗癌症 [2]。
在K562细胞中，PROTAC-O4I2（1µM；48h）诱导K562野生型细胞凋亡 [1]。在过表达SF3B1WT的K562细胞中，细胞毒性谱发生了逆转，使得 PROTAC-O4I2（1µM；72h）对细胞活力的抑制作用是Pladienolide B的两倍 [3]。
在患有肿瘤的果蝇模型中，施用PROTAC-O4I2（10μM；po；30d）显著降低了CRISPR/Cas9介导的Notch敲除（Notch-gRNA2x）动物肠道中的干细胞活性和肿瘤生长 [1]。