KX2-391 (Synonyms: KX 01, Tirbanibulin)

Cell lines

HCC cell lines Huh7, PLC/PRF/5, Hep3B, and HepG2

Preparation method

The solubility of this compound in DMSO is >121mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

6,564 to 0.012 nM, 3 days

Applications

KX2-391 showed dose-response curves against all four HCC cell lines Huh7, PLC/PRF/5, Hep3B, and HepG2 with the GI50 of 9 nM, 13 nM, 26 nM, and 60 nM, respectively. In NIH3T3/c-Src527F and SYF/c-Src527F cells, KX2-391 inhibited cell growth with the GI50 of 23 nM and 39 nM, respectively. KXO1 (10-30 nM) could halve proliferation rates (GI50) of a panel of human cancer cell lines known to have activated levels of SFK- such as HT-29 human colon cancer cells, as well as NIH3T3/c-Src527F cells. KXO1 inhibited anchorage-independent growth of HT-29 and 3T3/c-Src527F cells.

Animal models

nude mice bearing 50 cc HT-29 tumors

Dosage form

Oral administration, 5 mg/kg bid

Application

Treatment of nude mice bearing 50 cc HT-29 tumors with 5 mg/kg KXO1 bid p.o. resulted in a 70% reduction tumor growth, with no significant toxicity to the host as determined by weight loss.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1]. Lau G M, Lau G M, Yu G L, et al. Expression of Src and FAK in hepatocellular carcinoma and the effect of Src inhibitors on hepatocellular carcinoma in vitro[J]. Digestive diseases and sciences, 2009, 54(7): 1465-1474.

[2]. Fallah-Tafti A, Foroumadi A, Tiwari R, et al. Thiazolyl N-benzyl-substituted acetamide derivatives: synthesis, Src kinase inhibitory and anticancer activities[J]. European journal of medicinal chemistry, 2011, 46(10): 4853-4858.

[3]. Bu Y, Gao L, Smolinski M, et al. KXO1 (KX2-391), a Src-family kinase inhibitor targeting the peptide-binding domain, suppresses oncogenic proliferation in vitro and in vivo[J]. 2008.