| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| Targets |
The primary targets of BI-894999 are the bromodomain-containing proteins BRD2, BRD3, BRD4, and BRDT, which are members of the BET family of epigenetic readers. BI-894999 binds to these proteins with Kd values of 0.49-1.6 nM. It inhibits the binding of BRD4-BD1 and BRD4-BD2 to acetylated histones with IC50 values of 5 nM and 41 nM, respectively. The compound shows at least a 200-fold selectivity for BRD4-BD1 over other targets. By inhibiting BET proteins, BI-894999 disrupts the reading of epigenetic marks and suppresses oncogene expression.
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| ln Vitro |
BI-894999 demonstrates potent in vitro activity against BET proteins. It binds to BRD2/3/4 and BRDT with Kd values of 0.49-1.6 nM. The compound inhibits the binding of BRD4-BD1 and BRD4-BD2 to acetylated histones with IC50 values of 5 nM and 41 nM, respectively. Its high selectivity for BRD4-BD1 (at least 200-fold) makes it a valuable tool for studying the specific functions of BET proteins in cancer and other diseases.
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| ln Vivo |
In vivo data for BI-894999 are not extensively reported in the available literature. As a potent and selective BET inhibitor, the compound has potential for in vivo applications in hematological malignancies by repressing super-enhancer-driven oncogenes. However, specific in vivo efficacy data, including animal models, dosing regimens, and pharmacokinetic-pharmacodynamic relationships, are not detailed in the available sources. The compound is classified as a research-use-only chemical.
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| Enzyme Assay |
In vitro receptor binding assays for BI-894999 typically involve measuring its binding affinity to BET proteins. Recombinant bromodomain proteins (BRD2, BRD3, BRD4, BRDT) are incubated with a labeled acetylated peptide probe in the presence of varying concentrations of BI-894999. The displacement of the probe is measured, and the Kd or IC50 for binding is calculated. The compound shows Kd values of 0.49-1.6 nM for BRD2/3/4 and BRDT.
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| Cell Assay |
In vitro cellular assays for BI-894999 are performed in cancer cell lines to assess its effects on BET protein function and cell proliferation. Cells are treated with BI-894999, and the expression of BET target genes is measured by quantitative PCR. The compound's effects on cell viability and proliferation are assessed using cell viability assays. However, specific cellular assay protocols are not detailed in the available literature.
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| Animal Protocol |
In vivo animal studies with BI-894999 are not extensively documented in the available literature. Based on its inhibition of BET proteins, potential in vivo models could include xenograft models for hematological malignancies. In such studies, BI-894999 would be administered systemically, and tumor growth would be monitored. However, specific protocols are not detailed in the available sources.
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| ADME/Pharmacokinetics |
BI-894999 has a molecular weight of 429.51 and a molecular formula of C25H27N5O2. It is soluble in DMSO at 86 mg/mL. The compound is stable when stored as a powder at -20°C for up to 3 years or at 4°C for up to 2 years, and in solution at -80°C for up to 6 months or at -20°C for up to 1 month. Detailed pharmacokinetic parameters are not available in the literature.
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| Toxicity/Toxicokinetics |
Comprehensive toxicology data for BI-894999 are not extensively reported. The compound is classified as a research-use-only chemical and is not intended for human consumption. As a BET inhibitor, it may have effects on normal cellular processes that could contribute to toxicity. Specific toxicological data, including acute toxicity, genotoxicity, and target organ effects, are not reported in the available literature.
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| References | |
| Additional Infomation |
BI-894999 is a research-grade compound not approved for clinical use. Its primary application is as a pharmacological tool for studying BET proteins in epigenetics and cancer research. The compound is used to investigate the role of BET proteins in transcriptional regulation and to validate BET proteins as therapeutic targets for the treatment of hematological malignancies and other cancers.
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| Molecular Formula |
C25H27N5O2
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|---|---|
| Molecular Weight |
429.514185190201
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| Exact Mass |
429.22
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| Elemental Analysis |
C, 69.91; H, 6.34; N, 16.31; O, 7.45
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| CAS # |
1660117-38-3
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| PubChem CID |
90647162
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
3
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
32
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| Complexity |
755
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| Defined Atom Stereocenter Count |
1
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| SMILES |
O1CCC(C2C=C3C(=CN=2)N=C(C2C=C(C)C(N(C)N=2)=O)N3[C@@H](C)C2C=CC=CC=2)CC1
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| InChi Key |
QNFGQQDKBYVNAS-KRWDZBQOSA-N
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| 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
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| 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
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| Synonyms |
BI894999 BI-894999 BI 894999.
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~125 mg/mL (~291.03 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.84 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.84 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.84 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3282 mL | 11.6412 mL | 23.2823 mL | |
| 5 mM | 0.4656 mL | 2.3282 mL | 4.6565 mL | |
| 10 mM | 0.2328 mL | 1.1641 mL | 2.3282 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT02516553 | COMPLETEDWITH RESULTS | Drug: BI 894999 | NUT Carcinoma Neoplasms |
Boehringer Ingelheim | 2015-07-08 | Phase 1 |
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