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
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 |
mg/mL |
mM |
| Solubility |
| DMSO |
86.0 |
200.22 |
| Ethanol |
86.0 |
200.22 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
429.52
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.
1: Tontsch-Grunt U, Traexler PE, Baum A, Musa H, Marzin K, Wang S, Trapani F,
Engelhardt H, Solca F. Therapeutic impact of BET inhibitor BI 894999 treatment:
backtranslation from the clinic. Br J Cancer. 2022 Aug;127(3):577-586. doi:
10.1038/s41416-022-01815-5. Epub 2022 Apr 20. PMID: 35444289; PMCID: PMC9346113.
2: Schöffski P, Machiels JP, Rottey S, Sadrolhefazi B, Musa H, Marzin K, Awada
A. Phase Ia dose-escalation trial with the BET protein inhibitor BI 894999 in
patients with advanced or metastatic solid tumours. Eur J Cancer. 2023
Sep;191:112987. doi: 10.1016/j.ejca.2023.112987. Epub 2023 Jul 11. PMID:
37556913.
3: Tontsch-Grunt U, Rudolph D, Waizenegger I, Baum A, Gerlach D, Engelhardt H,
Wurm M, Savarese F, Schweifer N, Kraut N. Synergistic activity of BET inhibitor
BI 894999 with PLK inhibitor volasertib in AML in vitro and in vivo. Cancer
Lett. 2018 May 1;421:112-120. doi: 10.1016/j.canlet.2018.02.018. Epub 2018 Feb
14. PMID: 29454094.
4: 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.
