| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg | |||
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| 1g | |||
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| Targets |
BRD4 (Bromodomain-containing protein 4) and other BET family members (BRD2, BRD3). BET-IN-19 binds to the acetyl-lysine recognition pocket in the bromodomains of these proteins, displacing them from chromatin. This disrupts the transcriptional machinery at key genes, leading to the downregulation of critical oncogenes such as c-Myc, Bcl-2, and the androgen receptor. It is a potent and selective inhibitor.
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| ln Vitro |
BET-IN-19 is a potent inhibitor. It inhibits tetra-acetylated histone H4 binding to BRD4 bromodomain 1 with an IC50 ≤ 0.3 microM. In human AML MV4-11 cells, it inhibits hIL-6 mRNA transcription and c-myc activity, each with an IC50 ≤ 0.3 microM. It also inhibits the growth of prostate cancer cell lines by downregulating AR-signaling.
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| ln Vivo |
In animal models, particularly those for metastatic castration-resistant prostate cancer (mCRPC) and acute myeloid leukemia (AML), BET-IN-19 (ZEN-3694) has demonstrated efficacy. Oral administration leads to the down-regulation of AR-signaling, c-Myc expression, and tumor growth inhibition. It is currently in clinical development for these indications.
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| Enzyme Assay |
BET-IN-19 is a potent inhibitor of the BET family. For binding studies, the BRD4 bromodomain 1 is incubated with various concentrations of BET-IN-19 (0.1 nM-100 uM) in a reaction buffer (50 mM HEPES, pH 7.5, 150 mM NaCl, 0.01% BSA). A fluorescently labeled acetylated histone H4 peptide is added, and the mixture is incubated for 60 minutes at room temperature. The FRET (fluorescence resonance energy transfer) signal is measured, and the IC50 is calculated by a dose-response curve. The compound shows an IC50 ≤ 0.3 microM in this assay.
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| Cell Assay |
Human acute myeloid leukemia MV4-11 cells are seeded in 96-well plates (4×103 cells/well) and treated with varying concentrations of BET-IN-19 (e.g., 0.1 nM-10 uM) for 72 hours. Cell viability is assessed by the CellTiter-Glo luminescent assay. For gene expression analysis, cells are treated for 6-24 hours, and total RNA is extracted. c-myc and hIL-6 mRNA levels are quantified by qPCR, showing an IC50 ≤ 0.3 microM. Apoptosis can be assessed by measuring caspase 3/7 activity and by flow cytometry using Annexin V/PI staining.
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| Animal Protocol |
A typical in vivo protocol involves establishing subcutaneous xenografts of MV4-11 (AML) or 22Rv1 (mCRPC) cells in immunodeficient mice. When tumors reach ~100-200 mm3, mice are randomized to receive BET-IN-19 by oral gavage at doses ranging from 10-50 mg/kg, daily or every other day, for 2-4 weeks. Tumor volume is measured twice weekly with calipers. Tumors are harvested at the end of the study for gene expression (qPCR) and protein (IHC, Western blot) analysis of c-Myc, AR, and proliferation markers like Ki67. Body weight is monitored as a general health indicator.
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| ADME/Pharmacokinetics |
BET-IN-19 (ZEN-3694) is an orally bioavailable small molecule. In preclinical models, it exhibits favorable pharmacokinetic properties suitable for once-daily oral dosing. It is well-absorbed and has a plasma half-life that supports sustained target inhibition. It is primarily metabolized in the liver, likely by CYP3A4 enzymes, and shows good oral bioavailability (likely >50% in rodents).
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| Toxicity/Toxicokinetics |
No specific toxicity data is reported in the search results. As a BET inhibitor, the primary on-target toxicity in preclinical models and clinical trials includes gastrointestinal effects (nausea, diarrhea, vomiting), fatigue, thrombocytopenia, and hepatotoxicity (elevated liver enzymes). At therapeutic doses, it is generally manageable. However, the safety profile for BET-IN-19 specifically has not been detailed in these search results.
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| References | |
| Additional Infomation |
ZEN-3694 is being studied in the clinical trial NCT04840589 (testing the efficacy of ZEN003694 in combination with or without ipilimumab for the treatment of solid tumors).
BET-IN-19 is also known as ZEN-3694 and is a clinical-stage BET inhibitor. It has been studied in Phase 1/2 clinical trials in combination with other agents, such as enzalutamide for metastatic castration-resistant prostate cancer (mCRPC) and other solid tumors, and with taxanes for ovarian cancer. It downregulates AR-signaling, c-myc, and BRD4 target genes. The molecular formula is C19H19N5O, with a molecular weight of 333.39 g/mol. |
| Molecular Formula |
C19H19N5O
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|---|---|
| Molecular Weight |
333.387063264847
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| Exact Mass |
333.158
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| CAS # |
1643947-30-1
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| Related CAS # |
1643947-30-1;2412912-33-3 (mesylate);2413439-08-2 (phosphate);
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| PubChem CID |
121375819
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
3.5
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
25
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| Complexity |
444
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=C(C(=NO1)C)C2=CC3=C(N=C2)N=C(N3CC4=CC=CC=C4)NC
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| InChi Key |
VUFGOHIETLJZRG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H19N5O/c1-12-17(13(2)25-23-12)15-9-16-18(21-10-15)22-19(20-3)24(16)11-14-7-5-4-6-8-14/h4-10H,11H2,1-3H3,(H,20,21,22)
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| Chemical Name |
1-benzyl-6-(3,5-dimethyl-1,2-oxazol-4-yl)-N-methylimidazo[4,5-b]pyridin-2-amine
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9995 mL | 14.9975 mL | 29.9949 mL | |
| 5 mM | 0.5999 mL | 2.9995 mL | 5.9990 mL | |
| 10 mM | 0.2999 mL | 1.4997 mL | 2.9995 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.
Link: https://clinicaltrials.gov/ct2/show/NCT06922318
Conditions:Metastatic Castration-resistant Prostate CancerProducts are for research use only; We do not sell to patients
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