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GSK2636771

Name: GSK2636771
Brand: Selleck Chemicals
SKU: S8002
Rating: 5 (15 reviews)

Catalog No.S8002

For research use only.

GSK2636771 is a potent, orally bioavailable and selective inhibitor of PI3Kβ with >900-fold selectivity over PI3Kα/PI3Kγ and >10-fold over PI3Kδ. Sensitive to PTEN null cell lines.

CAS No. 1372540-25-4

Selleck's GSK2636771 has been cited by 15 publications

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PI3K Signaling Pathway Map

Biological Activity

Description

GSK2636771 is a potent, orally bioavailable and selective inhibitor of PI3Kβ with >900-fold selectivity over PI3Kα/PI3Kγ and >10-fold over PI3Kδ. Sensitive to PTEN null cell lines.

Targets

PI3Kβ ^[1]

In vitro

GSK-2636771 shows selectively inhibitory activity in PTEN null cell lines (human prostate adenocarcinoma PC-3 and breast cancer HCC70) with EC50 of 36 nM and 72 nM, respectively. ^[1] GSK2636771 significantly decreases cell viability in p110β-reliant PTEN-deficient PC3 prostate and BT549 and HCC70 breast cancer cell lines, and leads to a marked decrease of AKT phosphorylation only in the control prostate and breast cancer cell lines. ^[2]

In vivo

GSK-2636771 decreases phosphorylated protein kinase Akt (Ser473) levels in these xenograft models. GSK-2636771 (100 mg/kg) do not increase glucose/insulin levels in mice. ^[1]

Protocol (from reference)

Cell Research:

^[2]

Cell lines: p110β-reliant PTEN-deficient PC3 prostate and BT549 and HCC70 breast cancer cell lines.
Concentrations: ~10 μM
Incubation Time: 72 hours
Method:
Cells are plated in 96-well microtiter plates at densities ranging from 1,500 to 15,000 cells/well, optimized for untreated control cells to be 80-90% confluent at the endpoint of the experiment. After 24 h, cells are treated with serial dilutions (100pM to 10μM) of GSK2636771. Cell viability is assessed after 72 h of treatment by incubation with CellTiter Blue for 1.5 h. The drug concentration requires for survival of 50% of cells relative to untreated cells (surviving fraction 50, SF50) is determined using GraphPad Prism version 5.0d. Cell lines that fails to achieve the SF50 to a given drug are nominally assigned as the highest concentration screened (i.e. 10μM). At least three independent experiments in triplicate per cell line targeted drug are performed. Association between a mutation and response to a targeted agent is determined using a Fisher’s exact test (GraphPad Prism), and a two-tailed P value <0.05 is considered statistically significant.

Animal Research:

[3]

Animal Models: Balb-c nude mice
Dosages: 100 mg/kg
Administration: oral administration

References

Solubility (25°C)

In vitro

Chemical Information

Molecular Weight	433.42
Formula	C₂₂H₂₂F₃N₃O₃
CAS No.	1372540-25-4
Storage	3 years	-20°C	powder
Storage	2 years	-80°C	in solvent
Smiles	CC1=C(C=CC=C1C(F)(F)F)CN2C(=NC3=C(C=C(C=C32)N4CCOCC4)C(=O)O)C

Download GSK2636771 SDF

In vivo Formulation Calculator (Clear solution)

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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
NCT03131908	Active not recruiting	Drug: GSK2636771\|Drug: Pembrolizumab	Melanoma and Other Malignant Neoplasms of Skin\|Metastatic Melanoma	M.D. Anderson Cancer Center\|National Cancer Institute (NCI)\|National Institutes of Health (NIH)\|Merck Sharp & Dohme Corp.\|GlaxoSmithKline	July 17 2017	Phase 1\|Phase 2
NCT02215096	Completed	Drug: GSK2636771\|Drug: Enzalutamide	Neoplasms	GlaxoSmithKline	November 13 2014	Phase 1
NCT01458067	Completed	Drug: GSK2636771	Cancer	GlaxoSmithKline	November 10 2011	Phase 1

(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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