Size | Price | Stock | Qty |
---|---|---|---|
5mg |
|
||
10mg |
|
||
25mg |
|
||
50mg |
|
||
100mg |
|
||
250mg |
|
||
Other Sizes |
|
Purity: ≥98%
dBET6 is a novel, highly potent, selective and cell-permeable chemical degrader of BET bromodomain proteins based on PROTAC technology with an IC50 of 14 nM. It has potential antitumor activity. In contrast to the selective effect of bromodomain inhibition on transcription, BET degradation prompts a collapse of global elongation that phenocopies CDK9 inhibition. Notably, BRD4 loss does not directly affect CDK9 localization. These studies, performed in translational models of T cell leukemia, establish a mechanism-based rationale for the development of BET bromodomain degradation as cancer therapy.
ln Vitro |
dBET6 is a cell-permeable, extremely selective, and effective BET degrader with an IC50 of 14 nM. dBET6 (100 nM) degrades BRD4 to demonstrate anti-tumor efficacy against T-cell acute lymphoblastic leukemia (T-ALL) lines [1].
|
---|---|
ln Vivo |
dBET6 (7.5 mg/kg, oral, BID) lowers the leukemic load in a disseminated T-ALL mouse model [1].
|
References |
[1]. Winter GE, et al. BET Bromodomain Proteins Function as Master Transcription Elongation Factors Independent of CDK9 Recruitment. Mol Cell. 2017 Jul 6;67(1):5-18.e19
|
Molecular Formula |
C42H45CLN8O7S
|
---|---|
Molecular Weight |
841.3741
|
CAS # |
1950634-92-0
|
Appearance |
Typically exists as solids (or liquids in special cases) at room temperature
|
SMILES |
O=C(NCCCCCCCCNC(COC1=CC=CC(C(N2C(CC3)C(NC3=O)=O)=O)=C1C2=O)=O)C[C@H]4C5=NN=C(C)N5C6=C(C(C)=C(C)S6)C(C7=CC=C(Cl)C=C7)=N41
|
InChi Key |
JGQPZPLJOBHHBK-UFXYQILXSA-N
|
InChi Code |
InChI=1S/C42H45ClN8O7S/c1-23-24(2)59-42-35(23)37(26-13-15-27(43)16-14-26)46-29(38-49-48-25(3)50(38)42)21-33(53)44-19-8-6-4-5-7-9-20-45-34(54)22-58-31-12-10-11-28-36(31)41(57)51(40(28)56)30-17-18-32(52)47-39(30)55/h10-16,29-30H,4-9,17-22H2,1-3H3,(H,44,53)(H,45,54)(H,47,52,55)/t29-,30?/m0/s1
|
Chemical Name |
2-((S)-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-(8-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetamido)octyl)-acetamide
|
Synonyms |
dBET6; d BET6; d-BET6
|
HS Tariff Code |
2934.99.9001
|
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)
|
Solubility (In Vitro) |
DMSO : ~50 mg/mL (~59.43 mM)
|
---|---|
Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (2.97 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
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 (2.97 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 25.0 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 | 1.1885 mL | 5.9427 mL | 11.8854 mL | |
5 mM | 0.2377 mL | 1.1885 mL | 2.3771 mL | |
10 mM | 0.1189 mL | 0.5943 mL | 1.1885 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.
![]() Identification and Characterization of dBET6 as a Second-Generation BET Degrader.Mol Cell.2017 Jul 6;67(1):5-18.e19. th> |
---|
![]() Differential Transcriptional Consequence after BET Inhibition and Degradation.Mol Cell.2017 Jul 6;67(1):5-18.e19. td> |
![]() Disruption of Global Transcriptional Elongation by BET Degradation.Mol Cell.2017 Jul 6;67(1):5-18.e19. td> |
![]() dBET6 Efficacy and CRBN Dependence in T-ALL.Mol Cell.2017 Jul 6;67(1):5-18.e19. th> |
---|
![]() Quantitative Measurement of Drug Impact on Genome-wide BRD4 Load.Mol Cell.2017 Jul 6;67(1):5-18.e19. td> |
![]() BET Degradation Attenuates P-TEFb Activity Independent of Recruitment.Mol Cell.2017 Jul 6;6 td> |