LJI308

Catalog No.S7871 Batch:S787101

Technical Data

Formula	C₂₁H₁₈F₂N₂O₂
Molecular Weight	368.38	CAS No.	1627709-94-7
Solubility (25°C)*	In vitro	DMSO	40 mg/mL (108.58 mM)
		Water	Insoluble
		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

LJI308 is a potent, and pan-RSK (p90 ribosomal S6 kinase) inhibitor with IC50 of 6 nM, 4 nM, and 13 nM for RSK1, RSK2, and RSK3, respectively.

Targets

RSK2 ^[1]	RSK1 ^[1]	RSK3 ^[1]
4 nM	6 nM	13 nM

In vitro

In MDA-MB-231 and H358 cells, LJI308 blocks cellular inhibition of RSK and its phosphorylation of YB1 on Ser102 with EC50 of 0.2–0.3 μM, and thus inhibits cell growth. ^[1] In TNBC HTRY-LT cells, LJI308 also suppresses cell growth correlative with YB-1 inhibition. ^[2]

Protocol (from reference)

Kinase Assay:^{^[1]}	Inhibition of RSK1, RSK2, and RSK3 activity Enzymatic activity of RSK isoforms 1, 2, and 3 is assessed using recombinant full-length RSK protein. RSK1 (1 nM), RSK2 (0.1 nM), or RSK3 (1 nM) is allowed to phosphorylate 200 nM peptide substrate (biotin-AGAGRSRHSSYPAGT-OH) in the presence of ATP at concentration equal to the Km for ATP for each enzyme (RSK1- 5 μM, RSK2- 20 μM, RSK3- 10 μM) and appropriate dilutions of RSK inhibitors in 50 mM HEPES, pH 7.5, 10 mM MgCl₂, 1 mM DTT, 0.1% BSA Fraction V, 0.01% Tween-20. After 150 min at room temperature, the reaction is stopped with 60 mM EDTA and extent of peptide phosphorylation was determined using an anti-phospho-AKT substrate antibody and AlphaScreen reagents as described by the manufacturer.
Cell Assay:^{^[1]}	Cell lines MDA-MB-231 and H358 cells Concentrations ~100 μM Incubation Time 72 h Method Cell growth under attached conditions is assessed by plating 1000 cells per well on 96-well tissue culture-treated plates in cell growth medium. Appropriate dilutions of compound are 4 added medium above cells and cell growth was assessed after 72 hrs by addition of CellTiter Glo reagent according to manufacturer’s directions.

Kinase Assay:^{^[1]}

Inhibition of RSK1, RSK2, and RSK3 activity
Enzymatic activity of RSK isoforms 1, 2, and 3 is assessed using recombinant full-length RSK protein. RSK1 (1 nM), RSK2 (0.1 nM), or RSK3 (1 nM) is allowed to phosphorylate 200 nM peptide substrate (biotin-AGAGRSRHSSYPAGT-OH) in the presence of ATP at concentration equal to the Km for ATP for each enzyme (RSK1- 5 μM, RSK2- 20 μM, RSK3- 10 μM) and appropriate dilutions of RSK inhibitors in 50 mM HEPES, pH 7.5, 10 mM MgCl₂, 1 mM DTT, 0.1% BSA Fraction V, 0.01% Tween-20. After 150 min at room temperature, the reaction is stopped with 60 mM EDTA and extent of peptide phosphorylation was determined using an anti-phospho-AKT substrate antibody and AlphaScreen reagents as described by the manufacturer.

Cell Assay:^{^[1]}

Cell lines
MDA-MB-231 and H358 cells
Concentrations
~100 μM
Incubation Time
72 h
Method
Cell growth under attached conditions is assessed by plating 1000 cells per well on 96-well tissue culture-treated plates in cell growth medium. Appropriate dilutions of compound are 4 added medium above cells and cell growth was assessed after 72 hrs by addition of CellTiter Glo reagent according to manufacturer’s directions.

References

Selleck's LJI308 has been cited by 8 publications

Comprehensive multi-omics analysis reveals WEE1 as a synergistic lethal target with hyperthermia through CDK1 super-activation [ Nat Commun, 2024, 15(1):2089]	PubMed: 38453961
Fisetin induces DNA double-strand break and interferes with the repair of radiation-induced damage to radiosensitize triple negative breast cancer cells [ J Exp Clin Cancer Res, 2022, 41-1:256]	PubMed: 35989353
EGFR-phosphorylated GDH1 harmonizes with RSK2 to drive CREB activation and tumor metastasis in EGFR-activated lung cancer [ Cell Rep, 2022, 41(11):111827]	PubMed: 36516759
Two kinds of transcription factors mediate chronic morphine-induced decrease in miR-105 in medial prefrontal cortex of rats [ Transl Psychiatry, 2022, 12(1):458]	PubMed: 36316324
The Global Phosphorylation Landscape of SARS-CoV-2 Infection [ Cell, 2020, 182(3):685-712.e19]	PubMed: 32645325
The Global Phosphorylation Landscape of SARS-CoV-2 Infection [ Cell, 2020, 182(3):685-712.e19]	PubMed: 32645325
EIF1AX and RAS Mutations Cooperate to Drive Thyroid Tumorigenesis through ATF4 and c-MYC. [ Cancer Discov, 2019, 9(2):264-281]	PubMed: 30305285
Stress-Induced Phosphorylation of Nuclear YB-1 Depends on Nuclear Trafficking of p90 Ribosomal S6 Kinase [Tiwari A Int J Mol Sci, 2018, 19(8)]	PubMed: 30126195

RETURN POLICY
Selleck Chemical’s Unconditional Return Policy ensures a smooth online shopping experience for our customers. If you are in any way unsatisfied with your purchase, you may return any item(s) within 7 days of receiving it. In the event of product quality issues, either protocol related or product related problems, you may return any item(s) within 365 days from the original purchase date. Please follow the instructions below when returning products.

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.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.