Home PI3K/Akt/mTOR PI3K inhibitor - mTOR inhibitor - DNA-PK inhibitor Samotolisib (LY3023414) For research use only.

Samotolisib (LY3023414)

Synonyms: GTPL8918

Samotolisib (LY3023414, GTPL8918) is an oral ATP competitive inhibitor of the class I PI3K isoforms, mTOR and DNA-PK.

Samotolisib (LY3023414) Chemical Structure

Samotolisib (LY3023414) Chemical Structure

CAS No. 1386874-06-1

Purity & Quality Control

Samotolisib (LY3023414) Related Products

Signaling Pathway

PI3K Signaling Pathways

PI3K Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
KB-8-5-11 qHTS assay P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen, Potency=0.6513μM. 31515284
KB-3-1 qHTS assay P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen. 31515284
Click to View More Cell Line Experimental Data

Biological Activity

Description Samotolisib (LY3023414, GTPL8918) is an oral ATP competitive inhibitor of the class I PI3K isoforms, mTOR and DNA-PK.
Targets
class I PI3K isoforms [1] mTOR kinase [1] DNA-PK [1]
In vitro
In vitro 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[1].
Experimental Result Images Methods Biomarkers Images PMID
Western blot pS6K1 / S6K1 / pAKT-S473 / AKT1 / pERK / ERK p-mTOR / mTOR / ATG5 / Beclin-1 / p62 29228741
Growth inhibition assay Cell viability 29228741
In Vivo
In vivo In vivo, LY3023414 demonstrates high bioavailability and dose-dependent dephosphorylation of PI3K/AKT/mTOR pathway downstream substrates such as AKT, S6K, S6RP, and 4E-BP1 for 4 to 6 hours, reflecting the drug's half-life of 2 hours. Intermittent target inhibition is sufficient for its antitumor activity. LY3023414 shows time- and dose-dependent target inhibition in vivo. It is currently being evaluated in phase 1 and 2 trials for the treatment of human malignancies[1].
Animal Research Animal Models athymic nude, CD-1 nude and NMRI athymic nude mice(Xenograft tumors)
Dosages --
Administration p.o.
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02575703 Completed
Healthy
Eli Lilly and Company
 October 2015 Phase 1
NCT02536586 Completed
Neoplasm
Eli Lilly and Company
 September 2015 Phase 1
NCT02443337 Terminated
Non-small Cell Lung Cancer Metastatic
Eli Lilly and Company|SCRI Development Innovations LLC
 July 2015 Phase 2

Chemical Information & Solubility

Molecular Weight 406.48 Formula

C23H26N4O3
CAS No. 1386874-06-1 SDF Download Samotolisib (LY3023414) SDF
Smiles CC(CN1C2=C3C=C(C=CC3=NC=C2N(C1=O)C)C4=CC(=CN=C4)C(C)(C)O)OC
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 81 mg/mL ( (199.27 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 8 mg/mL

Water : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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