UNC-1215 Chemical Properties

Boiling point:

712.1±60.0 °C(Predicted)

Density 

1.224±0.06 g/cm3(Predicted)

storage temp. 

2-8°C

solubility 

DMSO: soluble5mg/mL, clear

form 

powder

pka

9.90±0.20(Predicted)

color 

white to beige

InChIKey

PQOOIERVZAXHBP-UHFFFAOYSA-N

SMILES

C1(C(N2CCC(N3CCCC3)CC2)=O)=CC=C(C(N2CCC(N3CCCC3)CC2)=O)C=C1NC1=CC=CC=C1

Safety Information

WGK Germany 

3

HS Code 

2933998090

UNC-1215 Usage And Synthesis

Uses

UNC 1215 is ; a potent, selective antagonist of L3MBTL3 with cellular activity. UNC1215 binds the MBT domains of L3MBTL3 with a Kd of 120 nM, competitively displacing mono- or dimethyl-lysine containing peptides

Definition

ChEBI: [3-anilino-4-[oxo-[4-(1-pyrrolidinyl)-1-piperidinyl]methyl]phenyl]-[4-(1-pyrrolidinyl)-1-piperidinyl]methanone is a member of benzamides and a N-acylpiperidine.

Biological Activity

UNC1215 is a potent, selective antagonist of L3MBTL3 with cellular activity. Lethal (3) malignant brain tumor-like protein 3 (L3MBTL3) is a putative polycomb group (PcG) protein with gene-repressing activity, a member of the MBT family of methyllysine binders. Methyl-lysine binding proteins are a family of proteins th at are important epigenetic regulators th at “read” the post-translational methylation state of histone lysine residues and modulate protein-protein interactions th at regulate gene expression. UNC1215 has an IC50 of 20 nM and > 100-fold selectivity over 13 HMTs and selected representatives of kinases, ion channels, 7TMs, and other epigenetic proteins. UNC1215 showed a significant decrease in FRAP recovery (Fluorescence Recovery After Photobleaching) time below 1 microM in cells using GFP-L3MBTL3. For full characterization details, please visit the UNC1215 probe summary on the Structural Genomics Consortium (SGC) website.

To learn about other SGC chemical probes for epigenetic targets, visit sigma.com/sgc

Synthesis

The general procedure for the synthesis of (2-(phenylamino)-1,4-phenylene)bis((4-(pyrrolidin-1-yl)piperidin-1-yl)methanone) from 2-(phenylamino)terephthalic acid and 4-pyrrolidin-1-yl-piperidine was as follows: 9.0 g of 2-(phenylamino)terephthalic acid was dissolved in 90 mL of N,N-dimethylformamide (DMF), 11.3 g of 1 -hydroxybenzotriazole (HOBt), 16.0 g 1 -ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDCI-HCl) and 14.2 g triethylamine (Et3N). The reaction was carried out in an ice bath under nitrogen protection for 1 hour. Subsequently, 10.8 g of 4-(1-pyrrolidinyl)piperidine dissolved in 50 mL of DMF was slowly added dropwise to the above reaction mixture and stirred at room temperature overnight. The following day, the completion of the reaction was monitored by thin layer chromatography (TLC). Upon completion of the reaction, the reaction was quenched with water, diluted with 200 mL of water and subsequently extracted with 200 mL of ethyl acetate (EA). The organic phases were combined and the pH of the aqueous phase was adjusted to about 3 with 3 M hydrochloric acid, the organic phase was separated and discarded. The aqueous phase pH was adjusted to 9-10 and the product was extracted with EA. The organic phases were combined, washed three times with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the solvent to give 18 g of crude product. The crude product was recrystallized with ethanol (EtOH)/EA/petroleum ether (PE) mixed solvent to give 16.4 g of white crystalline solid, the target compound (2-(phenylamino)-1,4-phenylene)bis((4-(pyrrolidin-1-yl)piperidin-1-yl)methanone) (UNC1215) in 88.7% yield.

target

L3MBTL3

References

[1] Patent: CN104072403, 2016, B. Location in patent: Paragraph 0037

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