LY3023414(Samotolisib)

Name: LY3023414(Samotolisib)
Brand: Selleck Chemicals
SKU: S8322
Rating: 5 (1 reviews)

For research use only. Not for use in humans.

Catalog No.S8322 Synonyms: GTPL8918

1 publication

LY3023414(Samotolisib) Chemical Structure

Molecular Weight(MW): 406.48

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

Selleck's LY3023414(Samotolisib) has been cited by 1 publication

Oncotarget, 2017, 8(58):98964-98973

PubMed: 29228741 ( click the link to review the publication )

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. LY3023414(Samotolisib) purchased from Selleck.

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Biological Activity

Description

LY3023414 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].

Assay

Methods	Test Index	PMID
Western blot	pS6K1 / S6K1 / pAKT-S473 / AKT1 / pERK / ERK; PubMed: 29228741 Oncotarget 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 Oncotarget 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 Oncotarget 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]	- Collapse Animal Models: athymic nude, CD-1 nude and NMRI athymic nude mice(Xenograft tumors) Formulation: 1% HEC in distilled water containing 0.25% polysorbate 80 and 0.05% Dow-Corning Antifoam 1510-US Dosages: -- Administration: p.o. (Only for Reference)

References

[1] Smith MC, et al. Mol Cancer Ther. 2016, [Epub ahead of print]

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 Download LY3023414(Samotolisib) SDF

Molecular Weight	406.48
Formula	C₂₃H₂₆N₄O₃
CAS No.	1386874-06-1
Storage	3 years -20°C powder
Storage	2 years -80°C in solvent
Synonyms	GTPL8918
Smiles	COC(C)CN1C(=O)N(C)C2=C1C3=CC(=CC=C3N=C2)C4=CC(=CN=C4)C(C)(C)O

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Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2019-10-14)

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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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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PI3K Signaling Pathway Map

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LY3023414(Samotolisib)