935693-62-2 Usage
Description
BIX 01294, 2-(Hexahydro-4-methyl-1H-1,4-diazepin-1-yl)-6,7-dimethoxy-N-[1-(phenylmethyl)-4-piperidinyl]-4-quinazolinamine hydrate trihydrochloride, is a cell-permeable diazepinyl-quinazolinamine compound that functions as a selective inhibitor of G9a histone methyltransferase (G9aHMTase; IC50 = 1.7 μM) and GLP HMTase (IC50 = 38 μM). It is a non-SAM (S-adenosylmethionine) analog-based HMTase inhibitor that can effectively interfere with the G9a-catalyzed H3K9me2 (histone H3 Lys9 dimethylation) modification in a reversible manner. BIX 01294 also exhibits the ability to induce autophagy and apoptosis in human neuroblastoma cells, particularly human bladder cancer cells, and has been shown to synergize with Oct3/4 and Klf4 in inducing reprogramming of primary murine fetal NPCs (Neural Progenitor Cells) into iPS (induced Pluripotent Stem) cells without additional viral transduction of Sox2 and c-Myc.
Uses
Used in Pharmaceutical Industry:
BIX 01294, 2-(Hexahydro-4-methyl-1H-1,4-diazepin-1-yl)-6,7-dimethoxy-N-[1-(phenylmethyl)-4-piperidinyl]-4-quinazolinamine hydrate trihydrochloride is used as a euchromatic histone-lysine N-methyltransferase 2 (EHMT2) inhibitor for its ability to induce autophagy and apoptosis in human neuroblastoma cells, specifically human bladder cancer cells. This makes it a potential candidate for the development of therapeutic agents targeting cancer treatment.
Used in Stem Cell Research:
In the field of stem cell research, BIX 01294, 2-(Hexahydro-4-methyl-1H-1,4-diazepin-1-yl)-6,7-dimethoxy-N-[1-(phenylmethyl)-4-piperidinyl]-4-quinazolinamine hydrate trihydrochloride is used as a reprogramming agent to facilitate the reactivation of pluripotency genes and induce passive demethylation, thus promoting the generation of induced Pluripotent Stem (iPS) cells. Its synergistic effect with Oct3/4 and Klf4 allows for the efficient reprogramming of primary murine fetal Neural Progenitor Cells into iPS cells without the need for additional viral transduction of Sox2 and c-Myc.
Used in Epigenetic Research:
BIX 01294, 2-(Hexahydro-4-methyl-1H-1,4-diazepin-1-yl)-6,7-dimethoxy-N-[1-(phenylmethyl)-4-piperidinyl]-4-quinazolinamine hydrate trihydrochloride is used as a research tool in epigenetic studies, specifically focusing on the role of histone methylation in gene regulation and cellular processes. Its ability to selectively inhibit G9a and GLP HMTases makes it a valuable compound for investigating the effects of histone methylation on various cellular functions and its potential implications in disease development.
Biological Activity
G9a-like protein and G9a histone lysine methyltransferase (HMTase) inhibitor (IC 50 values are 0.7 and 1.7 μ M respectively) that displays no activity at other HTMases up to 37 μ M. Modulates H3K9me2 levels in mammalian cells and potentiates induction of pluripotent stem cells from somatic cells in vitro .
References
1) Kubicek et al. (2007) Reversal of H3K9me2 by a small-molecule inhibitor for the G9a histone methyltransferase; Mol. Cell. 25 473
2) Huangfu et al. (2008) Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds; Nat. Biotechnol. 26 795
3) Shi et al., (2008) A combined chemical and genetic approach for the generation of induced pluripotent stem cells; Cell Stem Cell. 2 525
Check Digit Verification of cas no
The CAS Registry Mumber 935693-62-2 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 9,3,5,6,9 and 3 respectively; the second part has 2 digits, 6 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 935693-62:
(8*9)+(7*3)+(6*5)+(5*6)+(4*9)+(3*3)+(2*6)+(1*2)=212
212 % 10 = 2
So 935693-62-2 is a valid CAS Registry Number.
935693-62-2Relevant articles and documents
HISTONE DEACETYLASE AND HISTONE METHYLTRANSFERASE INHIBITORS AND METHODS OF MAKING AND USE OF THE SAME
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Page/Page column 46, (2018/02/28)
The compounds of formula (I) are dual inhibitors of the enzymes histone deacetylases (HDACs) and histone methyltransferase G9a, both of which are key posttranslational enzymes in cancer development.
Protein lysine methyltransferase g9a inhibitors: Design, synthesis, and structure activity relationships of 2,4-diamino-7-aminoalkoxy-quinazolines.
Liu, Feng,Chen, Xin,Allali-Hassani, Abdellah,Quinn, Amy M.,Wigle, Tim J.,Wasney, Gregory A.,Dong, Aiping,Senisterra, Guillermo,Chau, Irene,Siarheyeva, Alena,Norris, Jacqueline L.,Kireev, Dmitri B.,Jadhav, Ajit,Herold, J. Martin,Janzen, William P.,Arrowsmith, Cheryl H.,Frye, Stephen V.,Brown, Peter J.,Simeonov, Anton,Vedadi, Masoud,Jin, Jian
experimental part, p. 5844 - 5857 (2010/10/03)
Protein lysine methyltransferase G9a, which catalyzes methylation of lysine 9 of histone H3 (H3K9) and lysine 373 (K373) of p53, is overexpressed in human cancers. Genetic knockdown of G9a inhibits cancer cell growth, and the dimethylation of p53 K373 results in the inactivation of p53. Initial SAR exploration of the 2,4-diamino-6,7-dimethoxyquinazoline template represented by 3a (BIX01294), a selective small molecule inhibitor of G9a and GLP, led to the discovery of 10 (UNC0224) as a potent G9a inhibitor with excellent selectivity. A high resolution X-ray crystal structure of the G9a?10 complex, the first cocrystal structure of G9a with a small molecule inhibitor, was obtained. On the basis of the structural insights revealed by this cocrystal structure, optimization of the 7-dimethylaminopropoxy side chain of 10 resulted in the discovery of 29 (UNC0321) (Morrison Ki = 63 pM), which is the first G9a inhibitor with picomolar potency and the most potent G9a inhibitor to date.
