THK01

THK01 is a potent ROCK2 inhibitor with IC50 values of 5.7 and 923 nM for ROCK2 and ROCK1, respectively. THK01 inhibits breast cancer metastasis through the ROCK2-STAT3 signaling pathway. THK01 can be used in research of breast cancer[1].

Research Areas >> Cancer

Signaling Pathways >> Cell Cycle/DNA Damage >> ROCK

Signaling Pathways >> Stem Cell/Wnt >> ROCK

Signaling Pathways >> TGF-beta/Smad >> ROCK

ROCK2:5.7 nM (IC50)

ROCK1:923 nM (IC50)

THK01 (1.25-10 μM; 48 h) 以剂量依赖的方式抑制 MDA-MB-231 细胞的迁移和侵袭能力[1]。 THK01 (5 μM; 24 h; MDA-MB-231 细胞) 通过 STAT 信号通路抑制乳腺癌转移[1]。 THK01 (1.25-10 μM; 24 h; MDA-MB-231 细胞) 以剂量依赖性方式下调 STAT3Y705 的磷酸化水平，同时略微上调 STAT3S727 的水平[1]。 Western Blot Analysis[1] Cell Line: MDA-MB-231 cells Concentration: 5 μM Incubation Time: 24 hours Result: Down-regulated the phosphorylation levels (p-STAT) of STAT1, STAT2, and STAT3, up-regulated of p-STAT5A and STAT6. Western Blot Analysis[1] Cell Line: MDA-MB-231 cells Concentration: 1.25, 2.5, 5, 10 μM Incubation Time: 24 hours Result: Reduced the level of p-STAT3Y705 and increased the expression of p-STAT3S727 in MDA-MB-231 cells.

THK01 (15 mg/kg; i.v.; 雌性 BALB/c 裸鼠) 在体内抑制乳腺癌细胞转移[1]。 Animal Model: Female BALB/c nude mice with MDAMB-231-Luc-mcherry xenografts (6 weeks old, weight about 20 g)[1] Dosage: 15 mg/kg Administration: Intravenous injection; once a day for 43 days Result: Reduced the pulmonary metastasis of MDA-MB-231 in vivo with negligible toxicity.

[1]. Wang J, et, al. Discovery of unglycosylated indolocarbazoles as ROCK2 isoform-selective inhibitors for the treatment of breast cancer metastasis. Eur J Med Chem. 2023 Mar 15;250:115181.