| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
BRD9[1]
dBRD9 dihydrochloride targets BRD9 (bromodomain-containing protein 9), a member of the bromodomain and extra-terminal (BET) protein family. BRD9 is a component of the SWI/SNF chromatin remodeling complex and plays a role in regulating gene expression. By recruiting the cereblon E3 ubiquitin ligase via the pomalidomide moiety, the PROTAC induces ubiquitination and proteasomal degradation of BRD9. This targeted degradation eliminates BRD9 protein, disrupting its function in chromatin remodeling and gene regulation. |
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| ln Vitro |
In vitro, dBRD9 dihydrochloride exhibits potent and selective degradation of BRD9. The compound inhibits the proliferation of AML cell lines. In MOLM-13 cells, dBRD9 dihydrochloride shows an IC₅₀ of 56.6 nM. By degrading BRD9, the compound disrupts the function of the SWI/SNF chromatin remodeling complex, leading to anti-proliferative effects in BRD9-dependent cancer cells.
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| ln Vivo |
In vivo activity data for dBRD9 dihydrochloride are limited. Based on its potent in vitro degradation and anti-proliferative activity in AML cell lines, the compound is expected to demonstrate antitumor efficacy in animal models of BRD9-driven cancers. Typical in vivo studies for BRD9 degraders involve administration to tumor-bearing mouse models, with assessment of tumor growth inhibition and BRD9 degradation in tumors.
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| Enzyme Assay |
For non-cellular in vitro binding assays, dBRD9 dihydrochloride is evaluated for its binding affinity to BRD9 and cereblon. The compound's ability to simultaneously engage both BRD9 and cereblon E3 ligase is assessed using biophysical techniques such as surface plasmon resonance or isothermal titration calorimetry. The formation of the ternary complex is a prerequisite for targeted protein degradation.
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| Cell Assay |
For in vitro cellular assays, dBRD9 dihydrochloride is tested in BRD9-dependent cancer cell lines such as AML cell lines (e.g., MOLM-13). Cells are treated with serial dilutions of the compound, and BRD9 protein levels are measured by Western blot to determine the DC₅₀ for degradation. Cell proliferation and viability are assessed using standard assays. The compound's effects on downstream gene expression and chromatin remodeling are evaluated.
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| Animal Protocol |
For in vivo animal studies, dBRD9 dihydrochloride would typically be evaluated in xenograft mouse models of AML or other BRD9-driven cancers. Mice bearing established tumors are treated with the compound via intraperitoneal or oral administration. Tumor volumes are measured regularly, and BRD9 degradation and target gene expression changes are assessed in tumor tissues at study endpoint. Body weight and general health are monitored to evaluate tolerability.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for dBRD9 dihydrochloride are limited. As a PROTAC with a molecular weight of 856.75, the compound's pharmacokinetic properties are influenced by its large size and bifunctional nature. The compound is soluble in DMSO and can be formulated for in vivo administration. Further pharmacokinetic studies would be needed to fully characterize its absorption, distribution, metabolism, and excretion profile.
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| Toxicity/Toxicokinetics |
Toxicological data for dBRD9 dihydrochloride are limited. As a BRD9 degrader that eliminates a component of the SWI/SNF chromatin remodeling complex, the compound may have on-target effects on normal cellular functions. Comprehensive toxicology studies including acute and repeat-dose toxicity, genotoxicity, and organ-specific toxicity assessments would be required for therapeutic development. The compound is for research use only and not for human use.
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| References | |
| Additional Infomation |
dBRD9 dihydrochloride is a selective BRD9 PROTAC degrader composed of the BRD9 inhibitor BI 7273 conjugated to the cereblon E3 ligase ligand pomalidomide. The compound inhibits the proliferation of AML cell lines and has an IC₅₀ of 56.6 nM in MOLM-13 cells. It has a molecular formula of C₄₀H₄₇Cl₂N₇O₁₀ and a molecular weight of 856.75. dBRD9 dihydrochloride is used in cancer research.
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| Molecular Formula |
C40H47CL2N7O10
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|---|---|
| Molecular Weight |
856.75
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| Exact Mass |
855.276
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| CAS # |
2341840-98-8
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| Related CAS # |
dBRD9;2170679-45-3
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| PubChem CID |
138991768
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| Appearance |
Typically exists as solid at room temperature
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
13
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| Rotatable Bond Count |
18
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| Heavy Atom Count |
59
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| Complexity |
1500
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CN1C=C(C2=C(C1=O)C=NC=C2)C3=CC(=C(C(=C3)OC)CN(C)CC(=O)NCCOCCOCCNC4=CC=CC5=C4C(=O)N(C5=O)C6CCC(=O)NC6=O)OC.Cl.Cl
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| InChi Key |
CSEVDQHYSARWTE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C40H45N7O10.2ClH/c1-45(21-29-32(54-3)18-24(19-33(29)55-4)28-22-46(2)38(51)27-20-41-11-10-25(27)28)23-35(49)43-13-15-57-17-16-56-14-12-42-30-7-5-6-26-36(30)40(53)47(39(26)52)31-8-9-34(48)44-37(31)50;;/h5-7,10-11,18-20,22,31,42H,8-9,12-17,21,23H2,1-4H3,(H,43,49)(H,44,48,50);2*1H
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| Chemical Name |
2-[[2,6-dimethoxy-4-(2-methyl-1-oxo-2,7-naphthyridin-4-yl)phenyl]methyl-methylamino]-N-[2-[2-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethoxy]ethoxy]ethyl]acetamide;dihydrochloride
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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 | 1.1672 mL | 5.8360 mL | 11.6720 mL | |
| 5 mM | 0.2334 mL | 1.1672 mL | 2.3344 mL | |
| 10 mM | 0.1167 mL | 0.5836 mL | 1.1672 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.
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