1320288-19-4

Basic information

• Product Name: UNC 0631
• Synonyms: UNC 0631;UNC0631/UNC-0631;N-[1-(CyclohexylMethyl)-4-piperidinyl]-2-[hexahydro-4-(1-Methylethyl)-1H-1,4-diazepin-1-yl]-6-Methoxy-7-[3-(1-piperidinyl)propoxy]-4-quinazolinaMine;N-[1-(Cyclohexylmethyl)-4-piperidinyl]-2-[hexahydro-4-(1-methylethyl)-1H-1,4-diazepin-1-yl]-6-methoxy-7-[3-(1-piperidinyl)propoxy]-4-quinazolinamine UNC0631;UNC 0631, >=98%;N-(1-(cyclohexylmethyl)piperidin-4- yl)-2-(4-isopropyl-1,4-diazepan-1-yl)- 6-methoxy-7-(3-(piperidin-1- yl)propoxy)quinazolin-4-amine
• CAS NO: 1320288-19-4
• Molecular Formula: C₃₇H₆₁N₇O₂
• Molecular Weight: 635.92594
• EINECS: 604-604-1
• Product Categories: Amines, Aromatics, Heterocycles, Inhibitors, Pharmaceuticals, Intermediates & Fine Chemicals;Inhibitors
• Mol File: 1320288-19-4.mol
• Article Data: 1

Chemical Properties

• Boiling Point: 763.4±70.0 °C(Predicted)
• Appearance: /
• Density: 1.114±0.06 g/cm3(Predicted)
• Solubility: insoluble in H2O; ≥12.66 mg/mL in EtOH with ultrasonic; ≥18.35 mg/mL in DMSO with gentle warming
• PKA: 9.34±0.70(Predicted)
• CAS DataBase Reference: UNC 0631(CAS DataBase Reference)
• NIST Chemistry Reference: UNC 0631(1320288-19-4)
• EPA Substance Registry System: UNC 0631(1320288-19-4)

Safety Data

• Hazardous Substances Data: 1320288-19-4(Hazardous Substances Data)

Usage

Description

UNC 0631, also known as N-[1-(Cyclohexylmethyl)-4-piperidinyl]-2-[hexahydro-4-(1-methylethyl)-1H-1,4-diazepin-1-yl]-6-methoxy-7-[3-(1-piperidinyl)propoxy]-4-quinazolinamine, is a selective histone lysine methyltransferase (HMTase) inhibitor for G9a and GLP. It is a potent and selective inhibitor of G9a activity in vitro (IC50 = 4 nM) and G9a/GLP-mediated dimethylation of histone 3 on lysine 9 in MDA-MB-231 cells (IC50 = 25 nM). It potently inhibits G9a/GLP activity in a variety of cancer cell lines as well as in the human fetal lung IMR-90 cell line.

Uses

Used in Pharmaceutical Industry:
UNC 0631 is used as a histone lysine methyltransferase (HMTase) inhibitor for G9a and GLP for its ability to selectively inhibit G9a activity in vitro and G9a/GLP-mediated dimethylation of histone 3 on lysine 9 in MDA-MB-231 cells.
Used in Cancer Research:
UNC 0631 is used as a potent inhibitor of G9a/GLP activity in a variety of cancer cell lines, including MDA-MB-231 cells, for its ability to inhibit the activity of G9a/GLP and modulate histone methylation patterns, which can have potential therapeutic effects in cancer treatment.
Used in Epigenetic Research:
UNC 0631 is used as a tool compound in epigenetic research for its ability to selectively inhibit G9a and GLP, two important histone methyltransferases involved in the regulation of gene expression and chromatin structure. This can help researchers investigate the role of histone methylation in various biological processes and diseases.

Biological Activity

unc 0631 is a potent inhibitor of protein lysine methyltransferase g9a (also known as kmt1c or ehmt2) with the ic50 value of 4nm [1].unc 0631 has been revealed to inhibit the g9a in sahh-coupled with the ic50 of 4nm. besides, unc 0631 has been found to be highly potent in reducing h3k9me2 levels in mda-mb-231 cells with the icw ic50 of 25nm. in addition, unc 0631 has been shown the high in vitro potency against g9a and improved lipophilicity. besides, unc 0631 has also been reported to have low cell toxicity in mda-mb-231 cells with the ic50 value of 2.8μm in mtt assay. in different cell lines, unc 0631 has been demonstrated to potently reduce h3k9me2 levels with the icw ic50 of 25nm, 18nm, 26nm, 24nm, 51nm, 72nm and 46nm in mda-mb-231, mcf7, pc3, 22rv1, hct116 wt, hct 116 p53 and imr90 cell lines, respectively [1].

references

[1] liu f1, barsyte-lovejoy d, allali-hassani a, he y, herold jm, chen x, yates cm, frye sv, brown pj, huang j, vedadi m, arrowsmith ch, jin j.optimization of cellular activity of g9a inhibitors 7-aminoalkoxy-quinazolines. j med chem. 2011 sep 8;54( 17):6139-50.

Upstream product

• 574738-68-4 methyl 2-amino-5-methoxy-4-(3-(piperidin-1-yl)propoxy)benzoate 
• 927173-22-6 methyl 5-methoxy-2-nitro-4-(3-(piperidin-1-yl)propoxy)benzoate 
• 1350755-41-7 C₁₇H₂₁Cl₂N₃O₂ 
• 59039-61-1 1-isopropyl-1,4-diazepane 
• 3943-74-6 4-hydroxy-3-methoxybenzoic acid methyl ester 
• 111627-40-8 methyl 4-(3-chloropropoxy)-3-methoxybenzoate 
• 214470-57-2 methyl 4-(3-chloropropoxy)-5-methoxy-2-nitrobenzoate 

Relevant articles and documents

Optimization of cellular activity of G9a inhibitors 7-aminoalkoxy- quinazolines

Protein lysine methyltransferase G9a plays key roles in the transcriptional repression of a variety of genes via dimethylation of lysine 9 on histone H3 (H3K9me2) of chromatin as well as dimethylation of nonhistone proteins including tumor suppressor p53. We previously reported the discovery of UNC0321 (3), the most potent G9a inhibitor to date, via structure-based design and structure-activity relationship (SAR) exploration of the quinazoline scaffold represented by BIX01294 (1). Despite its very high in vitro potency, compound 3 lacks sufficient cellular potency. The design and synthesis of several generations of new analogues aimed at improving cell membrane permeability while maintaining high in vitro potency resulted in the discovery of a number of novel G9a inhibitors such as UNC0646 (6) and UNC0631 (7) with excellent potency in a variety of cell lines and excellent separation of functional potency versus cell toxicity. The design, synthesis, and cellular SAR of these potent G9a inhibitors are described.