[CAS NO. 1082949-68-5] LY-2584702tosylatesalt
PRODUCTS SPECIFICATIONS [1082949-68-5]
DESCRIPTION [1082949-68-5]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 617.62 |
| Molecular Formula | C28H27F4N7O3S |
| SMILES | CN1C=C(C2=CC=C(F)C(C(F)(F)F)=C2)N=C1C3CCN(C4=C5C(NN=C5)=NC=N4)CC3.O=S(C6=CC=C(C)C=C6)(O)=O |
6 Publications Citing Use of MCE
Summary
LY-2584702 tosylate salt is a selective ATP competitive inhibitor of p70S6K with an IC 50 of 4 nM. In S6K1 enzyme assay, the IC 50 of LY-2584702 is 2 nM.
IC50 & Target
|
p70S6K 4 nM (IC 50 ) |
In Vitro
LY-2584702 (LY2584702) inhibits phosphorylation of the S6 ribosomal protein (pS6) in HCT116 colon cancer cells with an IC 50 of 0.1-0.24 μM [1] . In S6K1 enzyme assay, the IC 50 of LY-2584702 (LY2584702) is 2 nM. For pS6 inhibition in cells, the IC 50 =100 nM. LY-2584702 has some activity against the S6K-related kinases MSK2 and RSK at high concentrations (enzyme assay IC 50 =58-176 nM). LY-2584702 inhibits S6K activity in EOMA cells, as determined by the phosphorylation of its downstream effector S6, in a dose-dependent manner [2] . Proliferation of A549 is significantly inhibited by LY-2584702 (LY2584702) treating over 24 h at 0.1 μM (P<0.05); and the trend of decline is more conspicuous with longer treatment and/or with the increased drug concentration (all P<0.05). Similar results are also observed in SK-MES-1, although the obvious inhibition is led by LY-2584702 at 0.6 μM (P<0.05), much higher than that of A549 [3] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
LY-2584702 demonstrates significant single-agent efficacy in both U87MG glioblastoma and HCT116 colon carcinoma xenograft models at two dose levels of 2.5 mg/kg twice daily (BID) and 12.5 mg/kg BID. LY-2584702 demonstrates statistically significant tumour growth reduction at TMED50 (threshold minimum effective dose 50%) (2.3 mg/kg) and TMED90 (10 mg/kg) in the HCT116 colon carcinoma xenograft model [1] . To examine the role of S6K in vivo, EOMA cells expressing shAkt3 are implanted in nu/nu mice, then treated for 14 days with LY-2584702 or Rapamycin. Analysis of tumors removed after 14 days shows that LY-2584702 inhibits S6 phosphorylation almost as effectively as Rapamycin. Loss of Akt3 increases tumor growth as compared with pLKO. LY-2584702 treatment alone does not significantly affect the growth of pLKO tumors. However, LY-2584702 significantly reduces the growth of tumors with shAkt3 [2] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT01372085 | Eli Lilly and Company |
Healthy Participants
|
June 2011 | Phase 1 |
| NCT01115803 | Eli Lilly and Company |
Metastases, Neoplasm|Carcinoma, Non-small Cell Lung|Renal Cell Carcinoma|Neuroendocrine Tumors
|
March 2010 | Phase 1 |
| NCT01241461 | Eli Lilly and Company |
Cancer
|
November 2010 | Phase 1 |
| NCT01394003 | Eli Lilly and Company |
Advanced Cancer
|
November 2008 | Phase 1 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Solvent & Solubility
DMSO : 10.25 mg/mL ( 16.60 mM ; Need ultrasonic and warming)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.6191 mL | 8.0956 mL | 16.1912 mL |
| 5 mM | 0.3238 mL | 1.6191 mL | 3.2382 mL |
| 10 mM | 0.1619 mL | 0.8096 mL | 1.6191 mL |
References
- [1] Tolcher A, et al. A phase I trial of LY2584702 tosylate, a p70 S6 kinase inhibitor, in patients with advanced solid tumors. Eur J Cancer. 2014 Mar;50(5):867-75.
- [2] Phung TL, et al. Akt1 and akt3 exert opposing roles in the regulation of vascular tumor growth. Cancer Res. 2015 Jan 1;75(1):40-50.
- [3] Chen B, et al. Hyperphosphorylation of RPS6KB1, rather than overexpression, predicts worse prognosis in non-small cell lung cancer patients. PLoS One. 2017 Aug 9;12(8):e0182891.