1620401-82-2

Basic information

• Product Name: UNC0379
• Synonyms: UNC0379;6,7-dimethoxy-2-(pyrrolidin-1-yl)-N-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine;6,7-dimethoxy-2-(pyrrolidin-1-yl)-N-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine UNC0379;UNC0379, >=98%;UNC03;6,7-Dimethoxy-2-(1-pyrrolidinyl)-N-[5-(1-pyrrolidinyl)pentyl]-4-quinazolinamine
• CAS NO: 1620401-82-2
• Molecular Formula: C23H35N5O2
• Molecular Weight: 413.57
• Product Categories: Inhibitors
• Mol File: 1620401-82-2.mol
• Article Data: 1

Chemical Properties

• Boiling Point: 606.3±65.0 °C(Predicted)
• Appearance: /
• Density: 1.168±0.06 g/cm3(Predicted)
• Storage Temp.: under inert gas (nitrogen or Argon) at 2–8 °C
• Solubility: Soluble in DMSO (up to 30 mg/ml)
• PKA: 10.54±0.20(Predicted)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 1 month.
• CAS DataBase Reference: UNC0379(CAS DataBase Reference)
• NIST Chemistry Reference: UNC0379(1620401-82-2)
• EPA Substance Registry System: UNC0379(1620401-82-2)

Safety Data

• Hazardous Substances Data: 1620401-82-2(Hazardous Substances Data)

Usage

Description

UNC0379 (CAS 1620401-82-2) is an inhibitor of the lysine methyltransferase SETD8 with selectivity over 15 other methyltransferases.1 IC50’s = 7.3 μM in a radioactive methyl transfer assay and 9.0 μM in an MCE assay. UNC0379 treatment of SY5Y and NGP neuroblastoma cell lines lead to activation of p53 and decreased tumor growth in an ex-vivo tumorigenicity assay.2

References

1) Ma et al. (2014), Discovery of a Selective, Substrate-Competitive Inhibitor of the Lysine Methyltransferase SETD8; J. Med. Chem. 57 6822 2) Veschi et al. (2017), Epigenetic siRNA and Chemical Screens Identify SETD8 Inhibition as a Therapeutic Strategy for p53 Activation in High-Risk Neuroblastoma; Cancer Cell 31 50

Upstream product

• 123-75-1 pyrrolidine 
• 71302-71-1 5-(pyrrolidin-1-yl)pentan-1-amine 
• 27631-29-4 2-chloro-6,7-dimethoxy-3H-quinazolin-4-one 

Relevant articles and documents

Structure-activity relationship studies of SETD8 inhibitors

SETD8 (also known as SET8, PR-SET7, or KMT5A (lysine methyltransferase 5A)) is the only known lysine methyltransferase that catalyzes the monomethylation of histone H4 lysine 20 (H4K20). In addition to H4K20, SETD8 monomethylates non-histone substrates such as the tumor suppressor p53 and the proliferating cell nuclear antigen (PCNA). Because of its role in regulating diverse biological processes, SETD8 has been pursued as a potential therapeutic target. We recently reported the first substrate-competitive SETD8 inhibitor, UNC0379 (1), which is selective for SETD8 over 15 other methyltransferases. We characterized this inhibitor in a battery of biochemical and biophysical assays. Here we describe our comprehensive structure-activity relationship (SAR) studies of this chemical series. In addition to 2- and 4-substituents, we extensively explored 6- and 7-substituents of the quinazoline scaffold. These SAR studies led to the discovery of several new compounds, which displayed similar potencies as compound 1 and interesting SAR trends. This journal is