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| 5mg |
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| 10mg |
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| 25mg |
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| 100mg |
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Purity: ≥98%
ARV-825 (ARV825) is a novel and potent BRD4 degrader based on PROTAC (proteolysis-targeting chimera) technology, anticancer activity. ARV-825 binds to BD1 and BD2 of BRD4 with Kds of 90 and 28 nM, respectively. BRD4, a bromodomain and extraterminal domain (BET) family member, is an attractive target in multiple pathological settings, particularly cancer. While BRD4 inhibitors have shown some promise in MYC-driven malignancies such as Burkitt's lymphoma (BL), BRD4 inhibitors lead to robust BRD4 protein accumulation, which may account for their limited suppression of MYC expression, modest antiproliferative activity, and lack of apoptotic induction. ARV-825 is a hetero-bifunctional PROTAC (Proteolysis Targeting Chimera) that recruits BRD4 to the E3 ubiquitin ligase cereblon, leading to fast, efficient, and prolonged degradation of BRD4 in all BL cell lines tested. Consequently, ARV-825 more effectively suppresses c-MYC levels and downstream signaling than small-molecule BRD4 inhibitors, resulting in more effective cell proliferation inhibition and apoptosis induction in BL. Cereblon-based PROTACs provide a better and more efficient strategy in targeting BRD4 than traditional small-molecule inhibitors.
| ln Vitro |
Transient chimera ARV-825 is a heterobifunctional protein that brings BRD4 to the brain of the E3 ubiquitin ligase. BRD4 is actively recruited by ARV-825 to the brain, which leads to the quick and effective proteosome-mediated destruction of both the cereblon-binding moieties of ARV-825 and BRD4. The Kd values for ARV-825's targets range from 28-90 nM and approximately 3 μM, respectively. These values indicate that ARV-825 mediates the substoichiometric conditioning process when BRD4 is introduced. On the other hand, ARV-825 therapy inhibited downstream signaling and extended BRD4 transcription [1].
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| References |
[1]. Lu J, et al. Hijacking the E3 Ubiquitin Ligase Cereblon to Efficiently Target BRD4. Chem Biol. 2015 Jun 18;22(6):755-63
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| Molecular Formula |
C46H47CLN8O9S
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|---|---|
| Molecular Weight |
923.4316
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| CAS # |
1818885-28-7
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| SMILES |
O=C(NC1=CC=C(OCCOCCOCCOCCNC2=CC=CC(C(N3C(CC4)C(NC4=O)=O)=O)=C2C3=O)C=C1)C[C@H]5C6=NN=C(C)N6C7=C(C(C)=C(C)S7)C(C8=CC=C(Cl)C=C8)=N5
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| InChi Key |
RWLOGRLTDKDANT-TYIYNAFKSA-N
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| InChi Code |
InChI=1S/C46H47ClN8O9S/c1-26-27(2)65-46-39(26)41(29-7-9-30(47)10-8-29)50-35(42-53-52-28(3)54(42)46)25-38(57)49-31-11-13-32(14-12-31)64-24-23-63-22-21-62-20-19-61-18-17-48-34-6-4-5-33-40(34)45(60)55(44(33)59)36-15-16-37(56)51-43(36)58/h4-14,35-36,48H,15-25H2,1-3H3,(H,49,57)(H,51,56,58)/t35-,36?/m0/s1
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| 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-(4-(2-(2-(2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethoxy)ethoxy)ethoxy)ethoxy)phenyl)acetamide
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| Synonyms |
ARV825; ARV-825; ARV 825.
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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 : ≥ 50 mg/mL (~54.15 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (2.71 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 (2.71 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 | 1.0829 mL | 5.4146 mL | 10.8292 mL | |
| 5 mM | 0.2166 mL | 1.0829 mL | 2.1658 mL | |
| 10 mM | 0.1083 mL | 0.5415 mL | 1.0829 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.
 Small molecule BRD4 inhibitors lead to significant BRD4 accumulation and inefficient c-MYC suppression.Chem Biol. 2015 Jun 18;22(6):755-63. |
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 Hijacking the E3 Ubiquitin Ligase Cereblon to create PROTAC to efficiently degrade BRD4.Chem Biol. 2015 Jun 18;22(6):755-63. |
 ARV-825 leads to more significant and longer lasting c-MYC suppression than small molecule inhibitors.Chem Biol. 2015 Jun 18;22(6):755-63. |
 ARV-825 leads to a superior effect on BL cells proliferation suppression than BRD4 inhibitors.Chem Biol. 2015 Jun 18;22(6):755-63. |
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ARV-825 leads to a superior effect on BL cells apoptosis induction than small molecule inhibitors.Chem Biol. 2015 Jun 18;22(6):755-63. |
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