Samotolisib (LY3023414)

For research use only.

Catalog No.S8322 Synonyms: GTPL8918

4 publications

Samotolisib (LY3023414) Chemical Structure

CAS No. 1386874-06-1

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

Selleck's Samotolisib (LY3023414) has been cited by 4 publications

1 Customer Review

  • The structure and formula weight of LY3023414 were presented (A). Established human glioma cells (U251MG and A172 lines), primary human astrocytes (“Astrocytes”) or primary human glioma cells [three lines, “Glioma (L1/2/3)”], were either left untreated (“Ctrl”) or treated with LY3023414 at 1-1000 nM, cells were further cultured for indicated time; Cell survival was tested (B, C, and E) (n=5). Cell proliferation was also tested by the BrdU ELISA assay (D and F) (n=5). *p < 0.05 vs. “Ctrl”. Experiments in this figure were repeated three times.

    Oncotarget, 2017, 8(58): 98964-98973. Samotolisib (LY3023414) purchased from Selleck.

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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

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].
Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
KB-8-5-11 MYjxTHRUKGG|c3H5 MWDQMYdtgWOxcILveIVqdiC|dXLzeJJifGW|IHnk[Y51cW[rZXSgbY4hU0JvOD21MVEyKGGmZX7vZ4Fz[2mwb33hJINmdGxibHnu[UwheUiWUzD0bIVz[XCndYTpZ{BtcWK{YYL5JJNkemWnbjygVI91\W6leU2wMlY2OTQQvF2u NXjtcHNJRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxM{G1NVUzQDRpPkOxOVE2Ojh2PD;hQi=>
KB-3-1 NEXwd2tyUFSVIHHzd4F6 M4G5bHAu\2y7Y3;wdo91\WmwIIP1ZpN1emG2ZYOgbYRmdnSrZnnl[EBqdiCNQj2zMVEh[WSnbn;jZZJkcW6xbXGgZ4VtdCCuaX7lMEByUFSVIITo[ZJieGW3dHnjJIxq[nKjcomgd4Nz\WWwLh?= NFHj[4M9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9|MUWxOVI5PCd-M{G1NVUzQDR:L3G+

... Click to View More Cell Line Experimental Data
Assay
Methods Test Index PMID
Western blot
pS6K1 / S6K1 / pAKT-S473 / AKT1 / pERK / ERK; 

PubMed: 29228741     


U251MG cells (A), primary human glioma cells [“Glioma (L1)”] (B) or primary human astrocytes (“Astrocytes”) (C) were either left untreated (“Ctrl”) or treated with LY3023414 (100 nM) for 1 hour, expressions of listed proteins were tested by Western blotting assay. Expressions of indicated proteins were quantified (total gray, vs. Tubulin). Experiments in this figure were repeated three times.

p-mTOR / mTOR / ATG5 / Beclin-1 / p62; 

PubMed: 29228741     


U251MG cells were pretreated with 3-methyladenine (3-MA, 10 mM), bafilomycin A1 (Baf A1, 1 μM) or chloroquine (Cq, 100 μM) for 1 hour, followed by LY3023414 (10/100 nM) treatment, cells were further cultured for indicated time.

29228741
Growth inhibition assay
Cell viability; 

PubMed: 29228741     


Established human glioma cells (U251MG and A172 lines), primary human astrocytes (“Astrocytes”) or primary human glioma cells were either left untreated (“Ctrl”) or treated with LY3023414 at 1-1000 nM, cells were further cultured for indicated time; Cell survival was tested.

29228741
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].

Protocol

Animal Research:

[1]
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  • Animal Models: athymic nude, CD-1 nude and NMRI athymic nude mice(Xenograft tumors)
  • Dosages: --
  • Administration: p.o.
    (Only for Reference)

Solubility (25°C)

In vitro Ethanol 61 mg/mL (150.06 mM)
DMSO 47 mg/mL (115.62 mM)
Water Insoluble

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 406.48
Formula

C23H26N4O3
CAS No. 1386874-06-1
Storage powder
in solvent
Synonyms GTPL8918
Smiles CC(CN1C2=C3C=C(C=CC3=NC=C2N(C1=O)C)C4=CC(=CN=C4)C(C)(C)O)OC

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Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT02575703 Completed Drug: [¹⁴C]-LY3023414 Healthy Eli Lilly and Company October 2015 Phase 1
NCT02536586 Completed Drug: LY3023414 Neoplasm Eli Lilly and Company September 2015 Phase 1
NCT02443337 Terminated Drug: LY3023414|Drug: Necitumumab Non-small Cell Lung Cancer Metastatic Eli Lilly and Company|SCRI Development Innovations LLC July 2015 Phase 2

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PI3K Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID