Barasertib (AZD1152-HQPA)

Cell lines

HL-60 cells

Preparation method

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

Reaction Conditions

25 nM, 72 hours

Applications

The cells exhibited increased DNA contents of 4N and 8N, indicative of polyploidy, within 24–48 h of treatment. After 48–72 h, barasertib-HQPA induced apoptotic cell death, as detected by an increased sub-G1 population compared for that of untreated cells. The induction of polyploidy was obvious at 24–48 h, and thereafter, the nuclei showed morphology typical of apoptosis, such as nuclear fragmentation and condensation. These observations were in accordance with the findings of the flow cytometric analysis.

Animal models

Female nude mice injected with SW620, Colo205 or HCT116 cells

Dosage form

Subcutaneous injection, 150 mg/kg/day, minipump infusion over 48 h

Applications

In SW620, HCT116 and Colo205 xenografts significant tumor growth inhibitions of 79% (P<0.001, day 23), 60% (P<0.001, day 25) and 81% (P<0.05, day 21) were observed, respectively. Colo205 xenografts appeared the most sensitive to treatment with a mean tumor volume (± SEM) on day 21 after cell implantation, of 0.42±0.19 cm3 for the barasertib group compared to 2.24±0.75 cm3 (P<0.05) for the vehicle control animals.

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] Yamauchi T, Uzui K, Shigemi H, et al. Aurora B inhibitor barasertib and cytarabine exert a greater-than-additive cytotoxicity in acute myeloid leukemia cells. Cancer science, 2013, 104(7): 926-933.

[2] Alferez D G, Goodlad R A, Odedra R, et al. Inhibition of Aurora-B kinase activity confers antitumor efficacy in preclinical mouse models of early and advanced gastrointestinal neoplasia. International journal of oncology, 2012, 41(4): 1475-1485.