CH7057288 is a novel, orally active TRK inhibitor. CH7057288 inhibits the activity of TRKA (IC50=1.1nM), TRKB (IC50=7.8nM), and TRKC (IC50=5.1nM) to block tumor cell proliferation, while also reducing tumor growth by inhibiting the MAPK and E2F signaling pathways. CH7057288 is suitable for research related to TRK fusion-positive cancers[1-2].
In vitro, treatment of TRK fusion-positive cell lines (such as NIH3T3 MPRIP-NTRK1 and CUTO-3) with CH7057288 (8.4–67nM) for 4–7 days. CH7057288 significantly inhibited cell proliferation[1]. CH7057288 (0.1µM-1mM) also inhibited the proliferation of TRK fusion-positive cell lines (including CUTO-3, KM12-Luc, and MO-91) after 4 or 7 days of treatment, by inhibiting TRK autophosphorylation to block MAPK and E2F signaling pathways[2].
In vivo, oral administration of CH7057288 (0.6-10mg/kg) once daily for 4 weeks to NCG mouse models bearing implanted TRK fusion-positive tumors (such as KM12-Luc). CH7057288 significantly inhibited tumor growth[2].
References:
[1] Ito T, Kinoshita K, Tomizawa M, et al. Discovery of CH7057288 as an Orally Bioavailable, Selective, and Potent pan-TRK Inhibitor. J Med Chem. 2022 Sep 22;65(18):12427-12444.
[2] Tanaka H, Sase H, Tsukaguchi T, et al. Selective TRK Inhibitor CH7057288 against TRK Fusion-Driven Cancer. Mol Cancer Ther. 2018 Dec;17(12):2519-2529.
CH7057288是一种新型的、具有口服活性的TRK抑制剂。CH7057288可抑制TRKA（IC50=1.1nM）、TRKB（IC50=7.8nM）和TRKC（IC50=5.1nM）的活性来阻断肿瘤细胞增殖，同时通过抑制MAPK和E2F信号通路以减少肿瘤生长，CH7057288可用于TRK融合阳性癌症的相关研究[1-2]。
在体外，CH7057288（8.4–67nM）处理TRK融合阳性细胞系（如NIH3T3 MPRIP-NTRK1、CUTO-3）4–7天。CH7057288显著抑制细胞增殖[1]。CH7057288（0.1μM-1mM）处理TRK融合阳性细胞系（CUTO-3、KM12-Luc、MO-91等）4天或7天，能够抑制细胞增殖，同时通过抑制TRK自身磷酸化来阻断其下游的MAPK和E2F信号通路[2]。
在体内，CH7057288（0.6-10mg/kg）每天一次口服给药，用于处理接种了TRK融合阳性肿瘤（如KM12-Luc）的NCG小鼠模型4周。CH7057288能够显著抑制肿瘤的生长[2]。