dBET23 is a novel and potent BRD4 degrader based on PROTAC technology. It degrades BRD4 BD1 with a DC50/5h of 50 nM.
Physicochemical Properties
| Molecular Formula | C43H45CLN8O9S |
| Molecular Weight | 885.383607625961 |
| Exact Mass | 884.271 |
| CAS # | 1957234-83-1 |
| PubChem CID | 124190790 |
| Appearance | Off-white to brown solid powder |
| LogP | 4.8 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 13 |
| Rotatable Bond Count | 18 |
| Heavy Atom Count | 62 |
| Complexity | 1730 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | ClC1C=CC(=CC=1)C1C2C(C)=C(C(NCCCCCCCCNC(COC3=CC=CC4=C3C(N(C4=O)C3C(NC(CC3)=O)=O)=O)=O)=O)SC=2N2C(C)=NN=C2[C@H](CC(=O)OC)N=1 |
| InChi Key | ZIHIUFZFPMILIG-XLTVJXRZSA-N |
| InChi Code | InChI=1S/C43H45ClN8O9S/c1-23-34-36(25-13-15-26(44)16-14-25)47-28(21-33(55)60-3)38-50-49-24(2)51(38)43(34)62-37(23)40(57)46-20-9-7-5-4-6-8-19-45-32(54)22-61-30-12-10-11-27-35(30)42(59)52(41(27)58)29-17-18-31(53)48-39(29)56/h10-16,28-29H,4-9,17-22H2,1-3H3,(H,45,54)(H,46,57)(H,48,53,56)/t28-,29?/m0/s1 |
| Chemical Name | Methyl 2-((6S)-4-(4-chlorophenyl)-2-((8-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetamido)octyl)carbamoyl)-3,9-dimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate |
| Synonyms | dBET23 dBET 23 dBET-23 |
| 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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | The usual binding sites of JQ1 and thalidomide on CRBN and BRD4BD1, respectively, are occupied by dBET23 [1]. |
| References |
[1]. Plasticity in binding confers selectivity in ligand-induced protein degradation. Nat Chem Biol. 2018;14(7):706-714. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~110 mg/mL (~124.24 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 4.25 mg/mL (4.80 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), suspension solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 42.5 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 | 1.1295 mL | 5.6473 mL | 11.2946 mL | |
| 5 mM | 0.2259 mL | 1.1295 mL | 2.2589 mL | |
| 10 mM | 0.1129 mL | 0.5647 mL | 1.1295 mL |