BIX 01294 Trihydrochloride

SKU: orb1226379

Description

BIX01294 is an inhibitor of G9a histone methyltransferase with IC50 of 2.7 μM in a cell-free assay, reduces H3K9me2 of bulk histones, also weakly inhibits GLP (primarily H3K9me3), no significant activity observed at other histone methyltransferases.

Key Properties

• CAS Number: 1392399-03-9
• MW: 600.02
• Purity: >98% (HPLC)
• Formula: C₂₈H₃₈N₆O₂·3HCl
• SMILES: Cl.Cl.Cl.COC1=C(OC)C=C2C(NC3CCN(CC4=CC=CC=C4)CC3)=NC(=NC2=C1)N1CCCN(C)CC1
• Target: HMTase
• Solubility: Ethanol: 8 mg/mL (13.33 mM); Water: 98 mg/mL (163.32 mM); DMSO: 98 mg/mL (163.32 mM)

Bioactivity

• In Vivo:
  BIX-01294 trihydrochloride (10 mg/kg; IP; three times a week for 2 weeks) significantly reduces tumor growth and tumor burden in recurrent tumor cells. Primary tumor growth is not inhibited. Animal model: Female MMTV-rtTA; TetO-Her2/neu (MTB; TAN) and TetO-Her2/neu (TAN) mice with recurrent or primary tumor cells. Dosage: 10 mg/kg. Administration: IP; three times a week for 2 weeks. Result: Significantly reduced tumor growth and tumor burden in recurrent tumor cells. Primary tumor growth was not inhibited. Slowed the growth of orthotopic recurrent tumors in athymic nude recipients.
• In Vitro:
  BIX-01294 (2 μM; 48 h) trihydrochloride selectively inhibits recurrent tumor cell growth. BIX-01294 (1 μM) trihydrochloride leads to a marked increase in phosphorylation of S345 of MLKL. BIX-01294 (1 μM) trihydrochloride significantly upregulates the canonical p53 targets Cdkn1a (p21) and Gadd45a in recurrent tumor cell lines. BIX-01294 (1 μM; 6 days) trihydrochloride causes the reduction in H3K9me2 levels in primary and recurrent tumor cells. BIX-01294 trihydrochloride leads to necroptotic cell death in recurrent tumor cells. Necrostatin-1 (30 μM) partially reverses cell death induced by BIX-01294 (750 nM; 24 h) trihydrochloride. BIX-01294 (4.1 μM; for 2 days) trihydrochloride causes around a 20% reduction, concomitant with a comparable increase in the unmodified H3K9 fragment in H3K9me2 in mouse ES cells. BIX-01294 trihydrochloride causes pronounced reduction in H3K9me2 and a small decrease for H3K9me3 and H3K9me1 in wild-type ES cells. BIX-01294 trihydrochloride has no inhibition of the other histone methyltransferases even at concentrations of 45 μM. BIX-01294 trihydrochloride does not affect SUV39H1 (H320R) and PRMT1 within the tested concentration range (up to 10 μM). BIX-01294 trihydrochloride inhibits G9a in an uncompetitive manner with S-adenosyl-methionine (SAM). BIX-01294 (1 μg/mL) causes reduction in the BrdU incorporation of fetal PASMCs. BIX-01294 treatment decreases the PASMCs migration induced by PDGF. Cell Viability Assay Cell line: Primary or recurrent tumor cells. Concentration: 2 μM. Incubation time: 48 h. Result: Selectively inhibited recurrent tumor cell growth.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Quick Database Links

Gene Symbol

HMTase