WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 206845
CAS#: 1660117-38-3
Description: BI-894999 is a potent and selective BET inhibitor potentially useful for the Treatment of hematological malignancies by repression of super-enhancer driven oncogenes. BI-894999 is a highly potent drug, particularly in hematological cell lines (n>40) such as MM, AML and lymphoma. BI 894999 treatment leads to G1 arrest and subsequent apoptosis. BI 894999 is found to regulate a very distinct set of genes. As already known.
MedKoo Cat#: 206845
Name: BI-894999
CAS#: 1660117-38-3
Chemical Formula: C25H27N5O2
Exact Mass: 429.2165
Molecular Weight: 429.524
Elemental Analysis: C, 69.91; H, 6.34; N, 16.31; O, 7.45
Synonym: BI-894999; BI894999; BI 894999.
IUPAC/Chemical Name: (S)-2,4-dimethyl-6-(1-(1-phenylethyl)-6-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)pyridazin-3(2H)-one
InChi Key: QNFGQQDKBYVNAS-KRWDZBQOSA-N
InChi Code: InChI=1S/C25H27N5O2/c1-16-13-21(28-29(3)25(16)31)24-27-22-15-26-20(19-9-11-32-12-10-19)14-23(22)30(24)17(2)18-7-5-4-6-8-18/h4-8,13-15,17,19H,9-12H2,1-3H3/t17-/m0/s1
SMILES Code: CN1C(C(C)=CC(C2=NC3=CN=C(C4CCOCC4)C=C3N2[C@@H](C)C5=CC=CC=C5)=N1)=O
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | BI 894999 is a BET inhibitor with IC50s of 5 nM and 41 nM for the binding of BRD4-BD1 and BRD4-BD2 to acetylated histones, respectively. |
| In vitro activity: | Treatment of MV-4-11B cells with BI 894999 for 72 h led to induction of a G1 arrest with an increase in cells in sub-G1, indicative for apoptosis (Suppl. Figure 2). Significant inhibition of proliferation was observed at concentrations of 10 nM BI 894999. Dose-dependent apoptosis peaked at around 40 h after the start of treatment (Suppl. Figure 3A, B). Reference: Oncogene. 2018 May;37(20):2687-2701. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5955861/ |
| In vivo activity: | For in vivo studies, BI 894999 was administered at daily oral doses of 2 or 4 mg/kg to mice engrafted intravenously with human MV-4-11B AML cells (Suppl. Table 5). This treatment resulted in tumor growth inhibition (TGI) of 96 or 99% and survival prolongation of 29.5 or 52 days, respectively (Fig. 2a). Reference: Oncogene. 2018 May;37(20):2687-2701. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5955861/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 86.0 | 200.22 | |
| Ethanol | 86.0 | 200.22 |
The following data is based on the product molecular weight 429.524 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Gerlach D, Tontsch-Grunt U, Baum A, Popow J, Scharn D, Hofmann MH, Engelhardt H, Kaya O, Beck J, Schweifer N, Gerstberger T, Zuber J, Savarese F, Kraut N. The novel BET bromodomain inhibitor BI 894999 represses super-enhancer-associated transcription and synergizes with CDK9 inhibition in AML. Oncogene. 2018 May;37(20):2687-2701. doi: 10.1038/s41388-018-0150-2. Epub 2018 Mar 1. PMID: 29491412; PMCID: PMC5955861. |
| In vitro protocol: | 1. Gerlach D, Tontsch-Grunt U, Baum A, Popow J, Scharn D, Hofmann MH, Engelhardt H, Kaya O, Beck J, Schweifer N, Gerstberger T, Zuber J, Savarese F, Kraut N. The novel BET bromodomain inhibitor BI 894999 represses super-enhancer-associated transcription and synergizes with CDK9 inhibition in AML. Oncogene. 2018 May;37(20):2687-2701. doi: 10.1038/s41388-018-0150-2. Epub 2018 Mar 1. PMID: 29491412; PMCID: PMC5955861. |
| In vivo protocol: | 1. Gerlach D, Tontsch-Grunt U, Baum A, Popow J, Scharn D, Hofmann MH, Engelhardt H, Kaya O, Beck J, Schweifer N, Gerstberger T, Zuber J, Savarese F, Kraut N. The novel BET bromodomain inhibitor BI 894999 represses super-enhancer-associated transcription and synergizes with CDK9 inhibition in AML. Oncogene. 2018 May;37(20):2687-2701. doi: 10.1038/s41388-018-0150-2. Epub 2018 Mar 1. PMID: 29491412; PMCID: PMC5955861. |
