LLY-283

Catalog No.S8883 Batch:S888301

Technical Data

Formula

C₁₇H₁₈N₄O₄

Molecular Weight

342.35

CAS No.

2040291-27-6

Solubility (25°C)*

In vitro

DMSO

68 mg/mL (198.62 mM)

Water

5 mg/mL (14.6 mM)

Ethanol

3 mg/mL (8.76 mM)

In vivo (Add solvents to the product individually and in order)

Clear solution

5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O

3.4mg/ml

Taking the 1 mL working solution as an example, add 50 μL 68 mg/ml clarified DMSO stock solution to 400 μL PEG300, mix evenly to clarify it; add 50 μL Tween80 to the above system, mix evenly to clarify it; then continue to add 500 μL ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

* <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

LLY-283 is a novel and selective inhibitor of protein arginine methyltransferase 5 (PRMT5). LLY-283 inhibits PRMT5 enzymatic activity in vitro and in cells with IC50 of 22 nM and 25 nM, respectively. LLY-283 shows antitumor activity.

Targets

PRMT5 ^[1] (Cell-free assay)	PRMT5 ^[1] (Cell-based assay)
22 nM	25 nM

In vitro

LLY-283 inhibits PRMT5 enzymatic activity in vitro and in cells with IC50 of 22 ± 3 and 25 ± 1 nM, respectively. LLY-283 directly binds to and occupies the SAM pocket. LLY-283 is a low nanomolar enzymatic inhibitor of the PRMT5:MEP50 complex in biochemical assays and is selective for PRMT5 over other methyltransferases including related family members.^[1]

In vivo

LLY-283 shows antitumor activity in mouse xenografts when dosed orally and can serves as an excellent probe molecule for understanding the biological function of PRMT5 in normal and cancer cells. LLY-283 can be used as an in vivo tool compound to evaluate the pharmacology of PRMT5 inhibition.^[1]

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines Sf9 cells, A375 tumor cells, MCF7 cells Concentrations 1 µM, 10 µM Incubation Time 48 h Method PRMT5 cellular assay. MCF7 cells are grown in DMEM supplemented with 10% FBS, penicillin (100 units/ml) and streptomycin (100 µg/ml). 40% confluent cells are treated with different concentrations of LLY-283 or DMSO control for 48 h. The levels of SmBB' and symmetrically dimethylated SmBB' are analyzed in westernblot.
Animal Study:^{^[1]}	Animal Models SCID mice with A375 derived xenografts Dosages 20 mg/kg Administration Oral gavage

Cell Assay:^{^[1]}

Cell lines
Sf9 cells, A375 tumor cells, MCF7 cells
Concentrations
1 µM, 10 µM
Incubation Time
48 h
Method
PRMT5 cellular assay. MCF7 cells are grown in DMEM supplemented with 10% FBS, penicillin (100 units/ml) and streptomycin (100 µg/ml). 40% confluent cells are treated with different concentrations of LLY-283 or DMSO control for 48 h. The levels of SmBB' and symmetrically dimethylated SmBB' are analyzed in westernblot.

Animal Study:^{^[1]}

Animal Models
SCID mice with A375 derived xenografts
Dosages
20 mg/kg
Administration
Oral gavage

References

[1] Zahid Q Bonday, et al. ACS Med Chem Lett. 2018 Apr 23;9(7):612-617.

Selleck's LLY-283 has been cited by 4 publications

Long non-coding RNA-derived peptides are immunogenic and drive a potent anti-tumour response [ Nat Commun, 2023, 14(1):1078]	PubMed: 36841868
Inhibition of histone methyltransferase PRMT5 attenuates cisplatin-induced hearing loss through the PI3K/Akt-mediated mitochondrial apoptotic pathway [ J Pharm Anal, 2023, 13(6):590-602]	PubMed: 37440906
A PRMT5 inhibitor protects against noise-induced hearing loss by alleviating ROS accumulation [ Ecotoxicol Environ Saf, 2022, 243:113992]	PubMed: 35994911
Explore the effect of LLY-283 on the ototoxicity of auditory cells caused by cisplatin: A bioinformatic analysis based on RNA-seq [ J Clin Lab Anal, 2022, e24176]	PubMed: 34997776

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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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