Samotolisib (LY3023414)

Catalog No.S8322 Synonyms: GTPL8918

For research use only.

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

Samotolisib (LY3023414) Chemical Structure

CAS No. 1386874-06-1

Selleck's Samotolisib (LY3023414) has been cited by 7 Publications

1 Customer Review

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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 MlfHdWhVWyCjc4PhfS=> MXzQMYdtgWOxcILveIVqdiC|dXLzeJJifGW|IHnk[Y51cW[rZXSgbY4hU0JvOD21MVEyKGGmZX7vZ4Fz[2mwb33hJINmdGxibHnu[UwheUiWUzD0bIVz[XCndYTpZ{BtcWK{YYL5JJNkemWnbjygVI91\W6leU2wMlY2OTQQvF2u MWK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{OTVzNUK4OEc,OzF3MUWyPFQ9N2F-
KB-3-1 NXjzS2l7eUiWUzDhd5NigQ>? NXH4PGd2WC2pbInjc5Bzd3SnaX6gd5Vje3S{YYTld{Bq\GWwdHnmbYVlKGmwIFvCMVMuOSCjZHXuc4NiemOrbn;tZUBk\WyuIHzpcoUtKHGKVGOgeIhmemGyZYX0bYMhdGmkcnHyfUB{[3KnZX6u MlK2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzF3MUWyPFQoRjNzNUG1Nlg1RC:jPh?=
Assay
Methods Test Index 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, 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 (from reference)

Animal Research:

[1]

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

Solubility (25°C)

In vitro

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

Chemical Information

Molecular Weight 406.48
Formula

C23H26N4O3

CAS No. 1386874-06-1
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CC(CN1C2=C3C=C(C=CC3=NC=C2N(C1=O)C)C4=CC(=CN=C4)C(C)(C)O)OC

In vivo Formulation Calculator (Clear solution)

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Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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Molarity Calculator

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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

(data from https://clinicaltrials.gov, updated on 2022-01-17)

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.

Handling Instructions

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