GSK2879552 2HCl

Catalog No.S7796 Batch:S779601

Technical Data

Formula	C₂₃H₂₈N₂O₂.2HCl
Molecular Weight	437.4	CAS No.	1902123-72-1
Solubility (25°C)*	In vitro	Water	44 mg/mL (100.59 mM)
		DMSO	29 mg/mL (66.3 mM)
		Ethanol	Insoluble
* <1 mg/ml means slightly soluble or 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. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description

GSK2879552 2HCl is a potent, selective, orally bioavailable, irreversible LSD1 inhibitor with K_i_app of 1.7 μM. Phase 1.

Targets

LSD1 ^[1]
(Cell-free assay)

1.7 μM(Ki)

In vitro

In 165 cell lines, GSK2879552 inhibits the growth of 9/28 small cell lung carcinoma (SCLC) lines and 20/29 AML lines ranged from 40% to 100%. The subset of SCLC lines and primary samples that undergo growth inhibition in response to GSK2879552 exhibit DNA hypomethylation of a signature set of probes. ^[1]

In vivo

In SCLC xenograft bearing mice, GSK2879552 (1.5 mg/kg, p.o.) demonstrates tumor growth inhibition by 17%-83%. ^[1]

Protocol (from reference)

Kinase Assay:^{^[1]}	LSD1 enzyme assay LSD1 activity was measured using a horseradish peroxidase (HRP) coupled assay with amplex red as an electron donor. The formation of product over time is measured using fluorescence intensity, Ex 531 nm and Em 595 nm, in a PerkinElmer EnVision plate reader. Final assay conditions are: 5 nM LSD1, 2.5 μM H3K4me2 peptide, 50 mM HEPES pH 7, 1 U/ml of HRP, 1 mM CHAPS, 0.03% dBSA and 10 μM amplex red.
Cell Assay:^{^[1]}	Cell lines 165 human cancer cell lines Concentrations ~10 μM Incubation Time 6 d Method The optimal cell seeding is determined empirically for all cell lines by examining the growth of a wide range of seeding densities in a 384-well format to identify conditions that permitted proliferation for 6 days. Cells are then plated at the optimal seeding density 24 h before treatment (in duplicate) with a 20-point twofold dilution series of GSK2879552 or 0.15% DMSO. Plates are incubated for 6 days at 37°C in 5% CO2. Cells are then lysed with CellTiter-Glo (CTG) (Promega) and chemiluminescent signal is detected with a TECAN Safire2 microplate reader. In addition, an untreated plate of cells is harvested at the time of compound addition (T0) to quantify the starting number of cells. CTG values obtained after the 6 day treatment are expressed as a percent of the T0 value and plotted against compound concentration. Data are fit with a four-parameter equation to generate a concentration response curve and the concentration of GSK126 required to inhibit 50% of growth (growth IC50) is determined.

Kinase Assay:^{^[1]}

LSD1 enzyme assay
LSD1 activity was measured using a horseradish peroxidase (HRP) coupled assay with amplex red as an electron donor. The formation of product over time is measured using fluorescence intensity, Ex 531 nm and Em 595 nm, in a PerkinElmer EnVision plate reader. Final assay conditions are: 5 nM LSD1, 2.5 μM H3K4me2 peptide, 50 mM HEPES pH 7, 1 U/ml of HRP, 1 mM CHAPS, 0.03% dBSA and 10 μM amplex red.

Cell Assay:^{^[1]}

Cell lines
165 human cancer cell lines
Concentrations
~10 μM
Incubation Time
6 d
Method
The optimal cell seeding is determined empirically for all cell lines by examining the growth of a wide range of seeding densities in a 384-well format to identify conditions that permitted proliferation for 6 days. Cells are then plated at the optimal seeding density 24 h before treatment (in duplicate) with a 20-point twofold dilution series of GSK2879552 or 0.15% DMSO. Plates are incubated for 6 days at 37°C in 5% CO2. Cells are then lysed with CellTiter-Glo (CTG) (Promega) and chemiluminescent signal is detected with a TECAN Safire2 microplate reader. In addition, an untreated plate of cells is harvested at the time of compound addition (T0) to quantify the starting number of cells. CTG values obtained after the 6 day treatment are expressed as a percent of the T0 value and plotted against compound concentration. Data are fit with a four-parameter equation to generate a concentration response curve and the concentration of GSK126 required to inhibit 50% of growth (growth IC50) is determined.

References

[1] Mohammad HP, et al. Cancer Cell. 2015, 28(1), 57-69.

Customer Product Validation

: Data from [Data independently produced by , , Br J Haematol, 2017, doi: 10.1111/bjh.14983]

Selleck's GSK2879552 2HCl has been cited by 24 publications

LSD1 inhibition improves efficacy of adoptive T cell therapy by enhancing CD8+ T cell responsiveness [ Nat Commun, 2024, 15(1):7366]	PubMed: 39191730
Transposable elements-mediated recruitment of KDM1A epigenetically silences HNF4A expression to promote hepatocellular carcinoma [ Nat Commun, 2024, 15(1):5631]	PubMed: 38965210
Pharmacological inhibition of LSD1 suppresses growth of hepatocellular carcinoma by inducing GADD45B [ MedComm (2020), 2023, 4(3):e269]	PubMed: 37250145
E3 ligase Trim35 inhibits LSD1 demethylase activity through K63-linked ubiquitination and enhances anti-tumor immunity in NSCLC [ Cell Rep, 2023, 10.1016/j.celrep.2023.113477]	PubMed: 37979167
Crucial Role of Lysine-Specific Histone Demethylase 1 in RANKL-Mediated Osteoclast Differentiation [ Int J Mol Sci, 2023, 24(4)3605]	PubMed: 36835016
Crucial Role of Lysine-Specific Histone Demethylase 1 in RANKL-Mediated Osteoclast Differentiation [ Int. J. Mol. Sci, 2023, 24(4)]	PubMed: None
Integrative analysis of drug response and clinical outcome in acute myeloid leukemia [ Cancer Cell, 2022, S1535-6108(22)00312-9]	PubMed: 35868306
Systematic identification of biomarker-driven drug combinations to overcome resistance [ Nat Chem Biol, 2022, 10.1038/s41589-022-00996-7]	PubMed: 35332332
TRACE generates fluorescent human reporter cell lines to characterize epigenetic pathways [ Mol Cell, 2021, S1097-2765(21)01037-6]	PubMed: 34963054
KRT6A Promotes Lung Cancer Cell Growth and Invasion Through MYC-Regulated Pentose Phosphate Pathway [ Front Cell Dev Biol, 2021, 9:694071]	PubMed: 34235156

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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