Cell lines

HCT116 colon cancer cells

Preparation method

The solubility of this compound in DMSO is >22.3mg/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.

Applications

In HCT116 colon cancer cells, LY2584702 inhibited phosphorylation of the S6 ribosomal protein (pS6) with an IC50 of 0.1-0.24 uM.

Animal models

U87MG glioblastoma and HCT116 colon carcinoma xenograft models

Dosage form

2.5 mg/kg twice daily (BID) and 12.5 mg/kg BID

Application

In both U87MG glioblastoma and HCT116 colon carcinoma xenograft models, LY2584702 exhibited significant single-agent efficacy.

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.

LY2584702 is a potent and selective inhibitor of p70 S6 kinase with IC50 value of 4 nM [1].

P70 S6 kinase (p70S6K) is a serine/threonine protein kinase that acts downstream of the phosphatidylinositol-3-kinase (PI3K)/Akt/mTOR signalling pathway. p70S6K phosphorylates the eukaryotic initiation factor 4B (eIF4B), a regulator of protein synthesis, and phosphorylates and activates ribosomal protein S6 (S6), a component of the 40S ribosomal subunit [1] [2].

LY2584702 is an oral and selective ATP competitive p70S6K inhibitor. In HCT116 colon cancer cells, LY2584702 inhibits phosphorylation of S6 (pS6) with IC50 value of 0.1-0.24 μM [1].

In the HCT116 colon carcinoma xenograft model, LY2584702 significantly inhibited tumour growth with threshold minimum effective dose 50% (TMED50) and TMED90 of 2.3 mg/kg and 10 mg/kg, respectively. In both HCT116 colon carcinoma and U87MG glioblastoma xenograft models, LY2584702 at levels of 2.5 mg/kg twice daily (BID) and 12.5 mg/kg BID exhibited significant efficacy. Treatment patients with advanced solid tumours with LY2584702 orally on a 28-day cycle, the maximum tolerated dose (MTD) was 75 mg BID (twice-daily) or 100 mg QD (once-daily) [1].

References:
[1].  Tolcher A, Goldman J, Patnaik A, et al. A phase I trial of LY2584702 tosylate, a p70 S6 kinase inhibitor, in patients with advanced solid tumours. Eur J Cancer, 2014, 50(5): 867-875.
[2].  Hollebecque A, Houédé N, Cohen EE, et al. A phase Ib trial of LY2584702 tosylate, a p70 S6 inhibitor, in combination with erlotinib or everolimus in patients with solid tumours. Eur J Cancer, 2014, 50(5): 876-884.