4-HPC was purchased from Toronto Research Chemicals, and GEM from Medchem Express. For in vitro assays, drugs were dissolved in DMSO and stored at −80°C, with the exception of CDDP, which was purchased as a 1 mg/mL solution in saline (Hospira). For in vivo administration, CPM (Endoxan, Baxter) was dissolved in saline and 120 mg/kg delivered intraperitoneally (i.p.) once weekly. CDDP and GEM were diluted in phosphate-buffered saline (PBS) and 3 mg/kg (i.p.) or 60 mg/kg (i.v.), respectively, were delivered once weekly. CHK inhibitors were purchased from Medchem Express except for
prexasertib (MedKoo Biosciences). AZD7762 was dissolved in 11%
cyclodextrin (Sigma) and 30 mg/kg delivered i.v. (22 (
link)), MK8776 was dissolved in 20% hydroxypropyl-β-
cyclodextrin (Sigma) and 40 mg/kg delivered i.p., and LY2606368-hydrochloride and
prexasertib were dissolved in 20%
Captisol (Medchem Express) and 20 mg/kg delivered i.v. once per day, or 10 mg/kg delivered s.c. twice in one day 10–12 h apart. LY2603618 was formulated for daily oral dosing (p.o.) at 200 mg/kg in 16.7%
Captisol in 25 mM phosphate buffer, pH 4 (59 (
link)). Treatment schedules are shown in figures and were repeated weekly for 6 weeks unless tumor-related morbidity or other ill health was observed.
Endersby R., Whitehouse J., Pribnow A., Kuchibhotla M., Hii H., Carline B., Gande S., Stripay J., Ancliffe M., Howlett M., Schoep T., George C., Andradas C., Dyer P., Schluck M., Patterson B., Tacheva-Gigorova S.K., Cooper M.N., Robinson G., Stewart C., Pfister S.M., Kool M., Milde T., Gajjar A., Johns T., Wechsler-Reya R.J., Roussel M.F, & Gottardo N.G. (2021). Small molecule screen reveals synergy of cell cycle checkpoint kinase inhibitors with DNA-damaging chemotherapies in medulloblastoma. Science translational medicine, 13(577), eaba7401.