LY294002

PI3K/AKT pathway inhibitor; Inhibits PI3K

LY294002

PI3K/AKT pathway inhibitor; Inhibits PI3K

From: 179 USD
Catalog #
72152_C
PI3K/AKT pathway inhibitor; Inhibits PI3K

Overview

LY294002 is a PI3K inhibitor that has greater potency and selectivity than quercetin, the structure on which it is based. LY294002 inhibits PI3K (IC₅₀ = 1.4 µM) and also shows activity against CK2, but not PI4K, EGFR, PDGFR, MAPK, PKA, or PKC. (Davies et al., Vlahos et al.)

MAINTENANCE AND SELF-RENEWAL
· Suppresses proliferation and self-renewal of mouse embryonic stem (ES) cells (Lianguzova et al., Paling et al.).

DIFFERENTIATION
· Promotes differentiation to insulin-producing cells from mouse ES cells (Hori et al.).
· Inhibits myotube formation from myoblasts (Coolican et al., Jiang et al.).
Alternative Names
Not applicable
Cell Type
Endoderm, PSC-Derived, Myogenic Stem and Progenitor Cells, Pluripotent Stem Cells
Species
Human, Mouse, Rat, Non-Human Primate, Other
Application
Differentiation
Area of Interest
Neuroscience, Stem Cell Biology
CAS Number
154447-36-6
Chemical Formula
C₁₉H₁₇NO₃
Molecular Weight
307.3 g/mol
Purity
≥ 98%
Pathway
PI3K/AKT
Target
PI3K

Protocols and Documentation

Find supporting information and directions for use in the Product Information Sheet or explore additional protocols below.

Document Type
Product Name
Catalog #
Lot #
Language
Product Name
LY294002
Catalog #
72152, 72154
Lot #
All
Language
English
Document Type
Safety Data Sheet
Product Name
LY294002
Catalog #
72152, 72154
Lot #
All
Language
English

Applications

This product is designed for use in the following research area(s) as part of the highlighted workflow stage(s). Explore these workflows to learn more about the other products we offer to support each research area.

Resources and Publications

Publications (7)

Deterministic Restriction on Pluripotent State Dissolution by Cell-Cycle Pathways. Gonzales KAU et al. Cell 2015 JUL

Abstract

During differentiation, human embryonic stem cells (hESCs) shut down the regulatory network conferring pluripotency in a process we designated pluripotent state dissolution (PSD). In a high-throughput RNAi screen using an inclusive set of differentiation conditions, we identify centrally important and context-dependent processes regulating PSD in hESCs, including histone acetylation, chromatin remodeling, RNA splicing, and signaling pathways. Strikingly, we detected a strong and specific enrichment of cell-cycle genes involved in DNA replication and G2 phase progression. Genetic and chemical perturbation studies demonstrate that the S and G2 phases attenuate PSD because they possess an intrinsic propensity toward the pluripotent state that is independent of G1 phase. Our data therefore functionally establish that pluripotency control is hardwired to the cell-cycle machinery, where S and G2 phase-specific pathways deterministically restrict PSD, whereas the absence of such pathways in G1 phase potentially permits the initiation of differentiation.
Phosphoinositide 3-kinase inhibitor LY294002 but not serum withdrawal suppresses proliferation of murine embryonic stem cells. Lianguzova MS et al. Cell biology international 2007 APR

Abstract

Mouse embryonic stem (mES) cells have short duration of their cell cycle and are capable of proliferating in the absence of growth factors. To find out which signaling pathways contribute to the regulation of the mES cell cycle, we used pharmacological inhibitors of MAP and PI3 kinase cascades. The MAP kinase inhibitors as well as serum withdrawal did not affect mES cell cycle distribution, whereas the inhibitor of PI3K activity, LY294002, induced accumulation of cells in G(1) phase followed by apoptotic cell death. Serum withdrawal also causes apoptosis, but it does not change the content and activity of cell cycle regulators. In contrast, in mES cells treated with LY294002, the activities of Cdk2 and E2F were significantly decreased. Interestingly, LY294002had a much stronger effect on cell cycle distribution in low serum conditions, implying that serum can promote G(1)--textgreaterS transition of mES cells by a LY294002-resistant mechanism. Thus, proliferation of mES cells is maintained by at least two separate mechanisms: a LY294002-sensitive pathway, which is active even in the absence of serum, and LY294002-resistant, but serum-dependent, pathway.
Regulation of embryonic stem cell self-renewal by phosphoinositide 3-kinase-dependent signaling. Paling NRD et al. The Journal of biological chemistry 2004 NOV

Abstract

The maintenance of murine embryonic stem (ES) cell self-renewal is regulated by leukemia inhibitory factor (LIF)-dependent activation of signal transducer and activator of transcription 3 (STAT3) and LIF-independent mechanisms including Nanog, BMP2/4, and Wnt signaling. Here we demonstrate a previously undescribed role for phosphoinositide 3-kinases (PI3Ks) in regulation of murine ES cell self-renewal. Treatment with the reversible PI3K inhibitor, LY294002, or more specific inhibition of class I(A) PI3K via regulated expression of dominant negative Deltap85, led to a reduction in the ability of LIF to maintain self-renewal, with cells concomitantly adopting a differentiated morphology. Inhibition of PI3Ks reduced basal and LIF-stimulated phosphorylation of PKB/Akt, GSK3alpha/beta, and S6 proteins. Importantly, LY294002 and Deltap85 expression had no effect on LIF-induced phosphorylation of STAT3 at Tyr(705), but did augment LIF-induced phosphorylation of ERKs in both short and long term incubations. Subsequently, we demonstrate that inhibition of MAP-Erk kinases (MEKs) reverses the effects of PI3K inhibition on self-renewal in a time- and dose-dependent manner, suggesting that the elevated ERK activity observed upon PI3K inhibition contributes to the functional response we observe. Surprisingly, upon long term inhibition of PI3Ks we observed a reduction in phosphorylation of beta-catenin, the target of GSK-3 action in the canonical Wnt pathway, although no consistent alterations in cytosolic levels of beta-catenin were observed, indicating this pathway is not playing a major role downstream of PI3Ks. Our studies support a role for PI3Ks in regulation of self-renewal and increase our understanding of the molecular signaling components involved in regulation of stem cell fate.

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