product name LY3023414
Description: LY3023414 (also known as GTPL8918) is an orally active, ATP competitive inhibitor of the class I PI3K isoforms, mTOR and DNA-PK. LY3023414 shows high solubility across a wide pH range. In vitro biochemical testing against approximately 266 kinases, LY3023414 was found to potently and selectively inhibit class I PI3K isoforms, mTORC1/2, as well as DNA-PK at low concentrations. In addition, inhibition of PI3K/AKT/mTOR signaling by LY3023414 led to G1 cell-cycle arrest and resulted in broad antiproliferative activity in cancer cell panel.
References: Mol Cancer Ther. 2016 Oct;15(10):2344-2356.
406.48
Formula
C23H26N4O3
CAS No.
1386874-06-1
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 47 mg/mL (115.6 mM)
Water: <1 mg/mL
Ethanol: 61 mg/mL (150.1 mM)
Solubility (In vivo)
Synonyms
GTPL8918
other peoduct :
| In Vitro |
In vitro activity: LY3023414 shows high solubility across a wide pH range. In vitro, inhibition of PI3K/AKT/mTOR signaling by LY3023414 causes G1 cell-cycle arrest and resulted in broad antiproliferative activity in cancer cell panel screens. In cell-based assays, LY3023414 inhibition of PI3K and mTOR is assessed in the PTEN-deficient U87 MG glioblastoma cell line. LY3023414 inhibits the phosphorylation of AKT at position T308 downstream of PI3K at an IC50 of 106 nM. Similarly, LY3023414 inhibits phosphorylation of AKT at position S473 (IC50 = 94.2 nM) by mTORC2 as well as phosphorylation of mTORC1 kinase targets p70S6K (position T389; IC50 =10.6 nM) and 4E-BP1 (positions T37/46; IC50 = 187 nM). The downstream phosphorylation of S6RP at positions pS240/244 (IC50 = 19.1 nM) by p70S6K was inhibited as well, indicating target inhibition along the entire PI3K/AKT/mTOR pathway by LY3023414. Kinase Assay: Cell Assay: In biochemical testing against approximately 266 kinases, LY3023414 was found to potently and selectively inhibit class I PI3K isoforms, mTORC1/2, as well as DNA-PK at low concentrations. In addition, inhibition of PI3K/AKT/mTOR signaling by LY3023414 led to G1 cell-cycle arrest and resulted in broad antiproliferative activity in cancer cell panel. |
|---|---|
| In Vivo | LY3023414 displayed high bioavailability and dose-dependent dephosphorylation of PI3K/AKT/mTOR pathway downstream substrates for 4 to 6 hours, indicating LY3023414s half-life of 2 hours. Moreover, equivalent total daily doses of LY3023414 given either once or twice daily could inhibit tumor growth to the similar extents in multiple xenograft models, demonstrating intermittent target inhibition was sufficient for antitumor activity. |
| Animal model | |
| Formulation & Dosage | |
| References | Mol Cancer Ther. 2016 Oct;15(10):2344-2356. |
