| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| Other Sizes |
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Purity: ≥98%
AT6 is a novel, potent and highly selective PROTAC-based BRD degrader, it is analog of AT1. Inducing macromolecular interactions with small molecules to activate cellular signaling is a challenging goal. PROTACs (proteolysis-targeting chimeras) are bifunctional molecules that recruit a target protein in proximity to an E3 ubiquitin ligase to trigger protein degradation. Structural elucidation of the key ternary ligase-PROTAC-target species and its impact on target degradation selectivity remain elusive.
| ln Vitro |
In order to cause protein degradation, bifunctional entities known as PROTACs (proteolysis-targeting chimaeras) enlist a target protein that is close to an E3 ubiquitin ligase. It is yet unclear how the target species' structural makeup affects the selectivity of target degradation by the important ternary ligase PROTAC. In the ternary complex, the ligand folds inward to permit the development of certain intermolecular interactions. Studies using isothermal titration calorimetry are compatible with the pronounced cooperative production of ternary complexes with Brd4BD2, which is corroborated by surface mutagenesis and proximity experiments. Compound AT1, which was created based on structure, shows extremely selective Brd4 depletion in cells[1].
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| References |
| Molecular Formula |
C48H58CLN9O7S3
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|---|---|
| Molecular Weight |
1004.67822599411
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| Exact Mass |
1003.33
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| CAS # |
2098836-50-9
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| PubChem CID |
124201839
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| Appearance |
White to off-white solid powder
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| LogP |
4.6
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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 |
20
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| Heavy Atom Count |
68
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| Complexity |
1740
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| Defined Atom Stereocenter Count |
4
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| SMILES |
CC1=C(SC2N3C(=NN=C3[C@H](CC(=O)NCCOCCOCCSC(C)(C)[C@H](NC(=O)C)C(N3C[C@H](O)C[C@H]3C(=O)NCC3C=CC(C4SC=NC=4C)=CC=3)=O)N=C(C3C=CC(Cl)=CC=3)C1=2)C)C
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| InChi Key |
ZCEIHPCVOJGWHG-TZPPCSJFSA-N
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| InChi Code |
InChI=1S/C48H58ClN9O7S3/c1-27-29(3)68-47-40(27)41(33-12-14-35(49)15-13-33)54-37(44-56-55-30(4)58(44)47)23-39(61)50-16-17-64-18-19-65-20-21-67-48(6,7)43(53-31(5)59)46(63)57-25-36(60)22-38(57)45(62)51-24-32-8-10-34(11-9-32)42-28(2)52-26-66-42/h8-15,26,36-38,43,60H,16-25H2,1-7H3,(H,50,61)(H,51,62)(H,53,59)/t36-,37+,38+,43-/m1/s1
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| Chemical Name |
(2S,4R)-1-[(2R)-2-acetamido-3-[2-[2-[2-[[2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetyl]amino]ethoxy]ethoxy]ethylsulfanyl]-3-methylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide
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| Synonyms |
AT6; AT-6; AT 6
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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: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). 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 : ~100 mg/mL (~99.53 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (4.98 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 50.0 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: ≥ 5 mg/mL (4.98 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 50.0 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. View More
Solubility in Formulation 3: ≥ 5 mg/mL (4.98 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.9953 mL | 4.9767 mL | 9.9534 mL | |
| 5 mM | 0.1991 mL | 0.9953 mL | 1.9907 mL | |
| 10 mM | 0.0995 mL | 0.4977 mL | 0.9953 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.
 The crystal structure of the Brd4BD2:MZ1:VHL-ElonginC-ElonginB complex.Nat Chem Biol.2017 May;13(5):514-521. |
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 Brd4BD2and VHL form a stable, cooperative complex in the presence of MZ1.
Schematic model of selective PROTAC-induced target degradation.Nat Chem Biol.2017 May;13(5):514-521. |
 The molecular basis of MZ1-induced compact complex formation between Brd4BD2and VHL.
Structure-guided design and characterization of Brd4-selective degrader AT1.Nat Chem Biol.2017 May;13(5):514-521. |
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