| Identification | Back Directory | [Name]
BI-9564 | [CAS]
1883429-22-8 | [Synonyms]
BI-9564
CS-2421
BI-9564 (BI 9564
BI-9564 >=97% (HPLC)
2,7-Naphthyridin-1(2H)-one, 4-[4-[(dimethylamino)methyl]-2,5-dimethoxyphenyl]-2-methyl-
4-[4-[(Dimethylamino)methyl]-2,5-dimethoxyphenyl]-2-methyl-1,2-dihydro-2,7-naphthyridin-1-one | [Molecular Formula]
C20H23N3O3 | [MDL Number]
MFCD30182324 | [MOL File]
1883429-22-8.mol | [Molecular Weight]
353.41 |
| Chemical Properties | Back Directory | [storage temp. ]
Store at -20°C | [solubility ]
≥8.82 mg/mL in DMSO with ultrasonic,≥8.32 mg/mL in EtOH with ultrasonic,insoluble in H2O | [form ]
crystalline solid | [color ]
White to off-white |
| Hazard Information | Back Directory | [Description]
BI-9564 is a selective inhibitor of BRD9 and BRD7 bromodomains (Kds = 14.1 and 239 nM; IC50s = 75 nM and 3.4 μM, respectively) that demonstrates cellular activity by semi-quantitative FRAP assay with ~90% inhibition of BRD9 and BRD7 at 0.1 μM and 1 μM, respectively. It does not bind to other bromodomain-containing BET family members (IC50s >100 μM as assessed by AlphaScreen), kinases, or G protein-coupled receptors and shows off-target selectivity only to the CECR2 bromodomain in in vitro ITC assays (Kd = 258 nM), but not in cell-based assays at concentrations up to 1 μM. BI-9564 has been shown to inhibit the growth of EOL-1 AML cells both in vitro (EC50 = 800 nM) and in a disseminated mouse model of AML (180 mg/kg/day). See the Structural Genomics Consortium (SGC) website for more information. | [Uses]
BI-9564 is a selective inhibitor of BRD9 and BRD7 bromodomains. It also exhibits antitumor activity in AML xenograft model. BI 9564 can be used as an epigentic probe to study bromodomain biology. | [in vitro]
bi-9564 was identified as a brd9/7 specific inhibitor via fragment-based screening and structure-guided design. bi-9564 was found to be bind to brd9 with a higher affinity than to brd7, and was negative on bet family proteins. in addition, bi-9564 demonstrated in vitro off-target selectivity to cecr2, but not in cells [1]. | [in vivo]
in animal study, bomtac:nmrifoxn1nu mice were given two oral doses daily and the concentration of bi-9564 in plasma was measured. dose-dependent aucs were obtained for bi-9564, achieving exposures that were higher compared to the ec50 level for eol-1 cells. moreover, when the oral treatment with bi-9564 at 180 mg/kg was initiated on day 5 and applied daily with an interruption at day 18 and 19, a significant reduction in tumour growth compared to controls was found on day 18 leading to a median tumour growth inhibition value of 52% [1]. | [IC 50]
75 nm and 3.4 μm for brd9 and brd7 bromodomains, respectively | [storage]
Store at -20°C | [References]
[1] martin lj et al. structure-based design of an in vivo active selective brd9 inhibitor. j med chem. 2016 may 26;59(10):4462-75. |
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