AZD-5438 (Synonyms: AZD 5438;AZD5438)

Cell lines

MCF-7 breast cancer cells,

Preparation method

The solubility of this compound in DMSO is >18.6mg/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

48 h

Applications

AZD5438 induced cell cycle arrest by inhibiting phosphorylation of cdk-dependent substrates, and exhibited the broad antiproliferative activity against asynchronous LoVo, MCF-7 and SW620 tumor cell lines. AZD5438 showed antiproliferative in a range of tumor cell lines including lung, colorectal, breast, prostate, and hematologic tumors with IC50 ranging from 0.2 μM (MCF-7) to 1.7 μM (ARH-77).

Animal models

Female nude mice bearing established BT474c, Colo-205, HX147, PC-3, and SW620 human tumor xenografts

Dosage form

Oral gavage, 37.5–75 mg/kg, once or twice daily for 3 wk

Application

In vivo, oral treatment of AZD5438 significantly inhibited the growth of human tumor xenografts derived from a wide range of different cancer types including breast, colon, lung, prostate, and ovarian with maximum TGI ranging from 38% to 153%. In the SW620 xenograft model, AZD5438 inhibited several cell cycle proteins such as, phH3, phosphonucleolin, PP1a, and several phospho-pRb epitopes in a dose-dependent manner.

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]. Byth K F, Thomas A, Hughes G, et al. AZD5438, a potent oral inhibitor of cyclin-dependent kinases 1, 2, and 9, leads to pharmacodynamic changes and potent antitumor effects in human tumor xenografts[J]. Molecular cancer therapeutics, 2009, 8(7): 1856-1866.