BIX 01294, 2-(Hexahydro-4-methyl-1H-1,4-diazepin-1-yl)-6,7-dimethoxy-N-[1-(phenylmethyl)-4-piperidinyl]-4-quinazolinamine hydrate trihydrochloride Chemical Properties

Boiling point:

654.6±65.0 °C(Predicted)

Density 

1.195±0.06 g/cm3(Predicted)

storage temp. 

2-8°C

solubility 

Soluble in DMSO (up to 50 mg/ml), or in Water (up to 50 mg/ml).

form 

Off-white solid

pka

9.34±0.70(Predicted)

color 

Off-white

Stability:

Stable for 1 year from date of purchase as supplied. Solutions in DMSO or distilled water may be stored at -20° for up to 3 months.

InChIKey

BZOWJAYUMMHCDW-UHFFFAOYSA-N

BIX 01294, 2-(Hexahydro-4-methyl-1H-1,4-diazepin-1-yl)-6,7-dimethoxy-N-[1-(phenylmethyl)-4-piperidinyl]-4-quinazolinamine hydrate trihydrochloride Usage And Synthesis

Description

BIX-01294 (935693-62-2) is a selective inhibitor of G9a histone methyltransferase (G9aHMTase; IC50 = 1.7 μM) as well as GLP HMTase (IC50 = 38 μM) leading to a decrease in H3K9me2(histone H3 lysine 9 methylation) in vitro.1 BIX-01294 facilitates the reactivation of pluripotency genes and induces passive demethylation, thus promoting reprogramming. BIX-01294, in combination with BAY K8644 (a calcium channel agonist), was found to improve reprogramming efficiencies of Oct4-Klf4-(OK)-infected neural progenitor cells.3

Uses

BIX 01294 is a euchromatic histone-lysine N-methyltransferase 2 (EHMT2) inhibitor, induces autophagy and apoptosis in human neuroblastoma cells, specifically human bladder cancer cells.

Definition

ChEBI: 6,7-dimethoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-[1-(phenylmethyl)-4-piperidinyl]-4-quinazolinamine is a member of piperidines.

General Description

A cell-permeable diazepinyl-quinazolinamine, non-SAM (S-adenosylmethionine) analog-based HMTase (histone methyltransferase) inhibitor that selectively interferes with the G9a-catalyzed H3K9me2 (histone H3 Lys9 dimethylation) modification (IC₅₀ = 1.7 μM) in a reversible manner. It inhibits the GLP-catalyzed H3K9me3 only at much higher concentrartions (IC₅₀ = 38 μM) and exhibits little activity against H3 methylations catalyzed by other HMTases (PRMT1, SET7/9, ESET, SUV39H1). Shown to effectively 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.

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 .

target

G9a-like protein

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

BIX 01294, 2-(Hexahydro-4-methyl-1H-1,4-diazepin-1-yl)-6,7-dimethoxy-N-[1-(phenylmethyl)-4-piperidinyl]-4-quinazolinamine hydrate trihydrochloride(935693-62-2)Related Product Information

• Resveratrol
• Sodium 2-propylpentanoate
• Vorinostat
• N,N'-[Sulfonylbis(1,4-phenylene)]bis(chloroacetamide)