1255580-76-7 Usage
Uses
Used in Pharmaceutical Industry:
UNC0638 is used as a selective HMTase inhibitor for G9a and GLP, targeting the enzymes responsible for histone methylation. This inhibition can lead to changes in gene expression and chromatin structure, making it a potential therapeutic agent for various diseases, including cancer.
Used in Cancer Research:
UNC0638 is used as a research tool in cancer biology to study the role of histone methylation in tumor development and progression. By inhibiting the activity of G9a and GLP, researchers can gain insights into the molecular mechanisms underlying cancer and identify potential therapeutic targets.
Used in Drug Development:
UNC0638 is used in the development of novel drugs targeting histone methylation, which can potentially lead to the discovery of new treatments for various diseases, including cancer. Its selective inhibition of G9a and GLP makes it a valuable compound for drug screening and optimization processes.
Used in Epigenetics Research:
UNC0638 is used as a research tool in the field of epigenetics to study the role of histone methylation in gene regulation and chromatin structure. By modulating the activity of histone methyltransferases, researchers can investigate the epigenetic mechanisms that control gene expression and cellular function.
Biological Activity
unc0638 is a potent and selective inhibitor of g9a and glp with ic50 values of < 15 nm and 19 ± 1 nm, respectively [1].glp forms a heterodimer with g9a. both g9a and glp can mono- and dimethylate histone h3 lys9 (h3k9), and dimethylate lys373 of p53 and hence inactivate the transcriptional activity of p53 [1].unc0638 showed balanced physicochemical properties and potency aiding cell penetration in vitro, had high potency in cellular assays. it was much less toxic than bix01294 to cells. in mda-mb-231 cells, in a concentration-dependent manner, exposure to unc0638 for 48 h reduced h3k9me2 levels with an ic50 value of 81 ± 9 nm (n= 3), which showed considerably higher potency than bix01294 (ic50= 500 ± 43 nm (n= 3)). in reducing h3k9me2 levels, unc0638 was of greater maximum effect than bix01294. this effect is close, but not equal, to the effect on the double knockdown of g9a and glp via shrna [1].in 6-week-old male athymic nude mice subcutaneously inoculated with bon cells, unc0638 decreased h3k9me2 level [2]. in organotypic cochlear cultures, rapid increase of h3k9me2 upon the damage of hair cells was observed. both ex vivo and in vivo, unc0638 effectively prevented aminoglycosides-induced hair cell damage [3].
references
[1]. vedadi m., barsyte-lovejoy d., liu f., et al. a chemical probe selectively inhibits g9a and glp methyltransferase activity in cells. nature chemical biology, 2011, 7:566-574.[2]. kim j.t., li j., jang e.r., et al. deregulation of wnt/β-catenin signaling through genetic or epigenetic alterations in human neuroendocrine tumors. clin. carcinogenesis, 2013, 00(00):1-9.[3]. yu h., lin q., wang y., et al. inhibition of h3k9 methyltransferases g9a/glp prevents ototoxicity and ongoing hair cell death. cell death and disease, 2013, 4:e506.
Check Digit Verification of cas no
The CAS Registry Mumber 1255580-76-7 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,2,5,5,5,8 and 0 respectively; the second part has 2 digits, 7 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 1255580-76:
(9*1)+(8*2)+(7*5)+(6*5)+(5*5)+(4*8)+(3*0)+(2*7)+(1*6)=167
167 % 10 = 7
So 1255580-76-7 is a valid CAS Registry Number.
1255580-76-7Relevant academic research and scientific papers
Optimization of cellular activity of G9a inhibitors 7-aminoalkoxy- quinazolines
Liu, Feng,Barsyte-Lovejoy, Dalia,Allali-Hassani, Abdellah,He, Yunlong,Herold, J. Martin,Chen, Xin,Yates, Christopher M.,Frye, Stephen V.,Brown, Peter J.,Huang, Jing,Vedadi, Masoud,Arrowsmith, Cheryl H.,Jin, Jian
, p. 6139 - 6150 (2011/10/09)
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.
