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Purity: ≥98%
dBET1 is a novel, potent, and competitive CRBN-based BET degrader (PROTAC) with an IC50 of 20 nM. It exhibits high selectivity among 7,429 proteins, only the expression of the oncoproteins MYC and PIM1, as well as BRD2, BRD3 and BRD4 are significantly downregulated by dBET1 treatment. BET degradation with dBET1 will likely reduce expression of pro-inflammatory genes in in vivo neuroinflammatory models associated with microglial/immune cell activation.
| ln Vitro |
Treatment with dBET1 inhibits the transcription of MYC and PIM1. The MV4;11 cell line exhibits more severe apoptotic effects when BRD4 is degraded by dBET1. Eight hours after dBET1 therapy, apoptosis was boosted and markedly elevated after just four hours. Additionally, throughout a 24-hour period, dBET1 exhibited a strong and superior reduction of MV4;11 cell growth (IC50= 0.14 μM as determined by ATP content, as opposed to IC50= 1.1 μM for JQ1) [1].
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| ln Vivo |
By using serial volume measurements, the administration of dBET1 lowered tumor weight and inhibited tumor development as measured postmortem. Four hours following the first or second daily treatment with dBET1 (50 mg/kg IP), there was acute pharmacodynamic degradation of BRD4. When dBET1 was used in place of vehicle controls in resected tumors, statistically significant BRD4 instability, MYC downregulation, and proliferation suppression were seen. Mice responded effectively to two weeks of dBET1, and there were no appreciable changes in body weight, hematocrit, platelet count, or white blood cell count [1].
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| References |
[1]. Winter GE, et al. DRUG DEVELOPMENT. Phthalimide conjugation as a strategy for in vivo target protein degradation. Science. 2015 Jun 19;348(6241):1376-81.
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| Molecular Formula |
C38H37CLN8O7S
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|---|---|
| Molecular Weight |
785.267785787582
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| CAS # |
1799711-21-9
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| Appearance |
Typically exists as solids (or liquids in special cases) at room temperature
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| SMILES |
CC(N(C1C2=NN=C(C)N2C3=C(C(C)=C(C)S3)C(C4=CC=C(Cl)C=C4)=N1)CCCCNC(COC5=CC=CC(C(N6C(CC7)C(NC7=O)=O)=O)=C5C6=O)=O)=O
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| InChi Key |
LNKVJWZPPUIOFG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C38H37ClN8O7S/c1-19-20(2)55-38-30(19)32(23-10-12-24(39)13-11-23)42-33(34-44-43-21(3)46(34)38)45(22(4)48)17-6-5-16-40-29(50)18-54-27-9-7-8-25-31(27)37(53)47(36(25)52)26-14-15-28(49)41-35(26)51/h7-13,26,33H,5-6,14-18H2,1-4H3,(H,40,50)(H,41,49,51)
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| Chemical Name |
N-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)-N-(4-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetamido)butyl)acetamide
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| Synonyms |
dBET1; d-BET-1; d BET 1; dBET-1; dBET 1; JQ1-Thalidomide conjugate
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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 : ~43.33 mg/mL (~55.18 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 3 mg/mL (3.82 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 30.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.2734 mL | 6.3672 mL | 12.7345 mL | |
| 5 mM | 0.2547 mL | 1.2734 mL | 2.5469 mL | |
| 10 mM | 0.1273 mL | 0.6367 mL | 1.2734 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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