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Samotolisib (LY3023414)

Name: Samotolisib (LY3023414)
Brand: Selleck Chemicals
SKU: S8322
Rating: 5 (7 reviews)

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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PI3K Signaling Pathway Map

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?=

Click to View More Cell Line Experimental Data

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.

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

Chemical Information

Molecular Weight	406.48
Formula	C₂₃H₂₆N₄O₃
CAS No.	1386874-06-1
Storage	3 years	-20°C	powder
Storage	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

Download Samotolisib (LY3023414) SDF

In vivo Formulation Calculator (Clear solution)

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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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