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Purity: ≥98%
dBRD9 (dBRD-9) is a novel and potent PROTAC degrader of the BRD9 bromodomain and the cereblon E3 ubiquitin ligase complex with anticancer activity. The bromodomain-containing protein BRD9, a subunit of the human BAF (SWI/SNF) nucleosome remodeling complex, has emerged as an attractive therapeutic target in cancer. Despite the development of chemical probes targeting the BRD9 bromodomain, there is a limited understanding of BRD9 function beyond acetyl-lysine recognition. dBRD9, as the first BRD9-directed chemical degraders, was created through iterative design and testing of heterobifunctional ligands that bridge the BRD9 bromodomain and the cereblon E3 ubiquitin ligase complex. Degraders of BRD9 exhibit markedly enhanced potency compared to parental ligands (10- to 100-fold). Parallel study of degraders with divergent BRD9-binding chemotypes in models of acute myeloid leukemia resolves bromodomain polypharmacology in this emerging drug class. Together, these findings reveal the tractability of non-BET bromodomain containing proteins to chemical degradation, and highlight lead compound dBRD9 as a tool for the study of BRD9.
| ln Vitro |
Actin, BRD4, and BRD7 expression are not significantly affected by dBRD9 (0.5-5000 nM; 4 h), although it does concentrate the reduction of BRD9 expression in MOLM-13 cells [1]. In MOLM-13 cells, dBRD9 (100 nM; 2 h) is selective for BRD9 [1]. EOL-1 and MOML-13 cell lines exhibit anti-proliferative effects from dBRD9 (7 d) [1].
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: MOLM-13 cells. Tested Concentrations: 0.5, 5, 50, 500 and 5000 nM. Incubation Duration: 4 hrs (hours). Experimental Results: The expression of BRD9 was diminished. |
| References |
[1]. Remillard D, et al. Degradation of the BAF Complex Factor BRD9 by Heterobifunctional Ligands. Angew Chem Int Ed Engl. 2017 May 15;56(21):5738-5743.
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| Molecular Formula |
C40H45N7O10
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|---|---|
| Molecular Weight |
783.826209783554
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| CAS # |
2170679-45-3
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| Related CAS # |
dBRD9 dihydrochloride;2341840-98-8
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| SMILES |
O=C(NCCOCCOCCNC1=CC=CC(C(N2C(CC3)C(NC3=O)=O)=O)=C1C2=O)CN(CC4=C(OC)C=C(C(C5=CC=NC=C65)=CN(C)C6=O)C=C4OC)C
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| InChi Key |
AIOCFZJGGGEWDK-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C40H45N7O10/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)
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| Chemical Name |
2-((2,6-Dimethoxy-4-(2-methyl-1-oxo-1,2-dihydro-2,7-naphthyridin-4-yl)benzyl)(methyl)amino)-N-(2-(2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethoxy)ethoxy)ethyl)acetamide
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| Synonyms |
dBRD-9; dBRD 9; dBRD9
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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 : ~100 mg/mL (~127.58 mM)
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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 | 1.2758 mL | 6.3789 mL | 12.7579 mL | |
| 5 mM | 0.2552 mL | 1.2758 mL | 2.5516 mL | |
| 10 mM | 0.1276 mL | 0.6379 mL | 1.2758 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.
 Design and characterization of thienopyridinone BRD9-targeted degraders.
Temporal and mechanistic characterization of BRD9 degradation by5. |
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 Performance of thienopyrininone degraders. Napthiridinone degrader6(dBRD9) offers improved biochemical and cellular selectivity.Angew Chem Int Ed Engl.2017May 15;56(21):5738-5743. |
 Impact of BRD9 degradation on cultured human leukemia lines.Angew Chem Int Ed Engl.2017May 15;56(21):5738- |
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