| Size | Price | Stock | Qty |
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| 1mg |
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| 100mg | |||
| Other Sizes |
| Targets |
PROTAC BRD9 Degrader-1 targets bromodomain-containing protein 9 (BRD9), a member of the bromodomain and extra-terminal (BET) family, which is a component of the BAF chromatin remodeling complex. The compound functions by simultaneously binding to BRD9 and the E3 ubiquitin ligase Cereblon, thereby inducing ubiquitination and subsequent proteasomal degradation of BRD9. This targeted degradation approach allows for selective elimination of BRD9 protein, providing a valuable tool for studying its biological functions in chromatin remodeling and transcriptional regulation.
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| ln Vitro |
BRD9, BRD4, and CRBN-DDB1 are all inhibited by PROTAC BRD9 Degrader-1 (Compound 1), with IC50 values of 13.5 nM, 3.78 μM, and 48.9 nM, respectively[1].
In vitro studies demonstrate that PROTAC BRD9 Degrader-1 is a highly potent chemical degrader with an IC₅0 of 13.5 nM. It effectively reduces BRD9 protein levels in cells through Cereblon-mediated proteasomal degradation. The compound exhibits excellent selectivity for BRD9 degradation and can be used as a selective probe for studying BAF complex biology. Its potent degradation activity makes it a valuable tool for investigating BRD9-dependent cellular processes and validating BRD9 as a therapeutic target in various disease contexts, particularly in cancers where BRD9 plays a critical role. |
| ln Vivo |
In vivo studies of PROTAC BRD9 Degrader-1 are primarily focused on evaluating its efficacy in animal models of diseases where BRD9 is implicated. As a potent BRD9 degrader with an IC₅0 of 13.5 nM, the compound is expected to demonstrate significant target degradation and therapeutic effects in vivo. The PROTAC mechanism enables catalytic degradation of BRD9, potentially achieving sustained target suppression with favorable pharmacokinetic properties. Further in vivo studies are needed to fully characterize its efficacy, safety, and pharmacokinetic profile in relevant disease models.
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| Enzyme Assay |
For in vitro enzyme/receptor binding assays, PROTAC BRD9 Degrader-1 can be evaluated using biochemical assays that measure the binding affinity to BRD9 and Cereblon. Surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC) can be employed to determine binding constants. The compound's ability to induce ternary complex formation between BRD9 and Cereblon can be assessed using biophysical methods such as AlphaScreen or TR-FRET assays. Standard assay conditions include physiological buffer systems with appropriate pH and ionic strength. Dose-response curves are generated to determine binding affinities and degradation potency.
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| Cell Assay |
For in vitro cellular experiments, PROTAC BRD9 Degrader-1 is tested in cell lines expressing BRD9 to evaluate its degradation efficacy. Cells are cultured in appropriate media and treated with various concentrations of the compound (typically ranging from nanomolar to micromolar). BRD9 protein levels are assessed by Western blotting or immunofluorescence to determine the extent of degradation. The kinetics and dose-dependence of degradation are characterized. Downstream effects on cell signaling, gene expression, and cell function are evaluated using qPCR, RNA sequencing, or functional assays. Cytotoxicity and cell viability are monitored using standard assays such as MTT or CellTiter-Glo.
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| Animal Protocol |
For in vivo animal experiments, PROTAC BRD9 Degrader-1 can be administered to mice via various routes including intraperitoneal injection or oral gavage, depending on its solubility and pharmacokinetic properties. The compound's in vivo efficacy can be evaluated in xenograft models or other relevant disease models. Target protein degradation in tissues is confirmed by Western blotting or immunohistochemistry. Pharmacodynamic markers and physiological parameters are measured to assess compound efficacy. Typical dosing regimens may range from 1 to 50 mg/kg administered daily or intermittently. Tumor volume, body weight, and overall health are monitored.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of PROTAC BRD9 Degrader-1 are not extensively detailed in the public literature. As a PROTAC molecule with a molecular weight of 903.98 g/mol, it may have limited oral bioavailability and may require parenteral administration for in vivo studies. The compound's solubility and stability in biological fluids would influence its pharmacokinetic profile. Detailed parameters such as Cₘₐₓ, Tₘₐₓ, AUC, half-life, and clearance would need to be determined through comprehensive PK studies. The compound's metabolism and excretion pathways remain to be fully characterized. Formulation development may be necessary for optimal in vivo administration.
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| Toxicity/Toxicokinetics |
Toxicological data for PROTAC BRD9 Degrader-1 are limited, as it is primarily a research tool. As a protein degrader that induces BRD9 degradation through the ubiquitin-proteasome pathway, its toxicity would depend on the importance of BRD9 for normal cellular function. BRD9 is a component of the BAF chromatin remodeling complex, and its degradation could have significant effects on gene expression and cell function. Comprehensive toxicology studies would be needed for further development. Appropriate safety precautions should be taken when handling this compound, including the use of personal protective equipment and adherence to institutional safety guidelines.
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| References | |
| Additional Infomation |
PROTAC BRD9 Degrader-1 is a research compound used for targeted protein degradation studies. No clinical trials or regulatory approvals have been reported for this compound as a therapeutic agent. It is available from various chemical suppliers for research purposes only. The compound is a leading PROTAC BRD9 chemical degrader with an IC₅0 of 13.5 nM and can be used as a selective probe for studying BAF complex biology. It represents a valuable tool for investigating BRD9 function and validating it as a therapeutic target.
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| Molecular Formula |
C42H45N7O12S2
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|---|---|
| Molecular Weight |
903.976407766342
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| Exact Mass |
903.256
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| CAS # |
2097971-01-0
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| PubChem CID |
137628637
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
0.8
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
14
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| Rotatable Bond Count |
16
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| Heavy Atom Count |
63
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| Complexity |
1960
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S1(CCC(CC1)/N=C(/C1=CC2C(N(C)C=C(C3C=CC(=C(C=3)OC)OCC(NCCCCNC(COC3=CC=CC4=C3C(N(C4=O)C3C(NC(CC3)=O)=O)=O)=O)=O)C=2S1)=O)\N)(=O)=O
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| InChi Key |
LOLHUPGCPDURJG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C42H45N7O12S2/c1-48-20-27(37-26(40(48)54)19-32(62-37)38(43)46-24-12-16-63(57,58)17-13-24)23-8-10-29(31(18-23)59-2)60-21-34(51)44-14-3-4-15-45-35(52)22-61-30-7-5-6-25-36(30)42(56)49(41(25)55)28-9-11-33(50)47-39(28)53/h5-8,10,18-20,24,28H,3-4,9,11-17,21-22H2,1-2H3,(H2,43,46)(H,44,51)(H,45,52)(H,47,50,53)
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| Chemical Name |
N-[4-[[2-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]oxyacetyl]amino]butyl]-2-[4-[2-[N'-(1,1-dioxothian-4-yl)carbamimidoyl]-5-methyl-4-oxothieno[3,2-c]pyridin-7-yl]-2-methoxyphenoxy]acetamide
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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 : ~150 mg/mL (~165.93 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (2.77 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 25.0 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: ≥ 2.5 mg/mL (2.77 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 25.0 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.1062 mL | 5.5311 mL | 11.0622 mL | |
| 5 mM | 0.2212 mL | 1.1062 mL | 2.2124 mL | |
| 10 mM | 0.1106 mL | 0.5531 mL | 1.1062 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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