UNC0379

Catalog No.S7570 Batch:S757002

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Technical Data

Formula

C23H35N5O2
Molecular Weight 413.56 CAS No. 1620401-82-2
Solubility (25°C)* In vitro DMSO 83 mg/mL (200.69 mM)
Ethanol 30 mg/mL (72.54 mM)
Water 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.)

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Biological Activity

Description UNC0379 is a selective, substrate competitive inhibitor of N-lysine methyltransferase SETD8 with IC50 of 7.3 μM, high selectivity over 15 other methyltransferases.
Targets
SETD8 [1]
(Cell-free assay)
7.3 μM
In vitro

UNC0379 is competitive with the peptide substrate and noncompetitive with the cofactor SAM. [1]
In vivo

UNC0379, a specific inhibitor of SET8 (a histone H4 lysine 20 (H4K20) monomethyltransferase, resulted in myofibroblast dedifferentiation may partly mitigate lung fibrosis without affecting the inflammatory responses.

Protocol (from reference)

Kinase Assay:

[1]
  • Microfluidic Capillary Electrophoresis Assay

    Inhibition of SETD8 methyltransferase activity is analyzed by monitoring decrease in methylation of the fluorescein labeled peptide, TW21. The test compounds are solubilized in 100% DMSO to 10 mM and then plated in Greiner 384-well polypropylene plates using 3-fold dilution scheme over 10 points spanning the concentration range from 3 mM to 0.15 μM using TECAN Genesis liquid handler. Then 1 μL of the serial dilution is transferred into compound dilution plate using Nanoscreen MultiMek liquid handling robot. Prior to performing the assay the compounds are diluted 10-fold in 1× assay buffer (20 mM Tris, pH 8.0, 25 mM NaCl, 2 mM DTT, and 0.05% Tween-20), and an amount of 2.5 μL of the resulting dilution is transferred into assay plate by Nanoscreen MultiMek liquid handling robot. To this plate 20 μL of 50 nM SETD8 and 2 μM TW21 peptide cocktail in 1× assay buffer are added using multidrop liquid dispenser. Following a 10 min incubation of the compounds with the enzyme/peptide mix, the reaction is initiated by adding 2.5 μL of 150 μM SAM in 1× buffer. For 100% inhibition controls 1× buffer is added instead of SAM. The reaction is allowed to proceed at room temperature for 120 min, and then the reaction is terminated by adding 35 μL of 0.08 ng/μL Endo-LysC protease solution. Following an additional 1 h incubation the plate is read on a Caliper Life Sciences EZ reader II using upstream voltage −500 V, downstream voltage −1800 V, and pressure of −1.5 psi. The IC50 values are determined using Screenable Solutions software.
Cell Assay:

[2]
  • Cell lines

    HEK293T cells

  • Concentrations

    10 μM

  • Incubation Time

    24 h

  • Method

    Cells were treated with indicated concentration of drug for 24 h.
Animal Study:

[3]
  • Animal Models

    Mice

  • Dosages

    1 mg/kg

  • Administration

    i.t.

Selleck's UNC0379 has been cited by 11 publications

Targeted inhibition of the methyltransferase SETD8 synergizes with the Wee1 inhibitor adavosertib in restraining glioblastoma growth [ Cell Death Dis, 2023, 10.1038/s41419-023-06167-3] PubMed: 37758718
Targeted inhibition of the methyltransferase SETD8 synergizes with the Wee1 inhibitor adavosertib in restraining glioblastoma growth [ Cell Death Dis, 2023, 14(9):638] PubMed: 37758718
SETD8, a frequently mutated gene in cervical cancer, enhances cisplatin sensitivity by impairing DNA repair [ Cell Biosci, 2023, 13(1):107] PubMed: 37308924
SETD8, a frequently mutated gene in cervical cancer, enhances cisplatin sensitivity by impairing DNA repair [ Cell Biosci, 2023, 13(1):107] PubMed: 37308924
CDC20 Is Regulated by the Histone Methyltransferase, KMT5A, in Castration-Resistant Prostate Cancer [ Cancers (Basel), 2023, 15(14)3597] PubMed: 37509260
H4K20me1 plays a dual role in transcriptional regulation of regeneration and axis patterning in Hydra [ Life Sci Alliance, 2023, 6(5)e202201619] PubMed: 36944423
SETD8 induces stemness and epithelial-mesenchymal transition of pancreatic cancer cells by regulating ROR1 expression [ Acta Biochim Biophys Sin (Shanghai), 2021, gmab140] PubMed: 34599596
The microtubule-associated histone methyltransferase SET8, facilitated by transcription factor LSF, methylates α-tubulin. [ J Biol Chem, 2020, 10.1074/jbc.RA119.010951] PubMed: 32111740
Epigenetic silencing of the synthesis of immunosuppressive Siglec ligand glycans by NF-κB/EZH2/YY1 axis in early-stage colon cancers [ Biochim Biophys Acta Gene Regul Mech, 2019, 1862(2):173-183] PubMed: 30716533
Epigenetic Reprogramming with Antisense Oligonucleotides Enhances the Effectiveness of Androgen Receptor Inhibition in Castration-Resistant Prostate Cancer [ Cancer Res, 2018, 78(20):5731-5740] PubMed: 30135193

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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.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.