DBET 1
dBET1
CAS: 1799711-21-9
Molecular Formula: C38H37ClN8O7S
DBET 1 - Names and Identifiers
DBET 1 - Physico-chemical Properties
| Molecular Formula | C38H37ClN8O7S |
| Molar Mass | 785.27 |
| Density | 1.55±0.1 g/cm3(Predicted) |
| Melting Point | 186 - 187°C |
| Solubility | DMSO : 50 mg/mL (63.67 mM);H2O : < 0.1 mg/mL (insoluble) |
| Appearance | Solid |
| Color | Pale Yellow |
| pKa | 10.68±0.40(Predicted) |
| Storage Condition | Hygroscopic, -20°C Freezer, Under inert atmosphere |
| Stability | Hygroscopic |
| In vitro study | dBET1 treatment can down-regulate the expression of MYC and PIM1, and does not affect the transcription of BRD4 and brd3. The transcription of BRD2 and the protein stability of its gene product are affected by dbet1. After 24 hours of treatment, dBET1 effectively inhibited the proliferation of MV4;11 cells, IC50 = 0.14 μm. Exposure of cells from patients with primary leukemia to dBET1 can cause depletion of BRD4 in a dose ratio, leading to apoptosis. dBET1-mediated targeted degradation of the BET protein inhibits the pro-inflammatory response in LPS-stimulated microglia. That is, dbet1-induced depletion of BRD2 and BRD4 and LPS-induced significant decrease in COX-2, iNOS protein levels, pro-inflammatory genes Nos2, Il-1β, Il-6, TNFα, Ccl2, Ptgs2, decreased levels of Mmp9 transcription are associated. |
| In vivo study | In a mouse model inoculated with human MV4;11 leukemia cells, administration of dBET1 attenuated tumor progression and reduced tumor weight. Intraperitoneal injection of 50 mg/kg dBET1, detection of its pharmacokinetic properties: 50 mg/kg dose can guarantee drug exposure, Cmax = 392 nM, Tmax = 0.5 hr, terminal t 1/2=6.69 hr, AUC last = 2109 hr * ng/ml, AUC INF = 295 hr * ng/ml. Mice treated with dBET1 for two weeks were well tolerated, with no significant changes in body weight, white blood cell count, hematocrit, or platelet count. |
DBET 1 - Preparation solution concentration reference
| 1mg | 5mg | 10mg | |
|---|---|---|---|
| 1 mM | 1.273 ml | 6.367 ml | 12.735 ml |
| 5 mM | 0.255 ml | 1.273 ml | 2.547 ml |
| 10 mM | 0.127 ml | 0.637 ml | 1.273 ml |
| 5 mM | 0.025 ml | 0.127 ml | 0.255 ml |
Last Update：2024-01-02 23:10:35
DBET 1 - Reference Information
| biological activity | dBET1 is a CRBN-based BET degrading agent with an IC50 of 20 nM for BRD4 and high selectivity. Among the 7429 detected proteins, only the expression of tumor proteins MYC, PIM1 and BRD2, BRD3 and BRD4 decreased significantly after dBET1. |
| target | TargetValue BRD4 () 20 nM |
| Target | Value |
| BRD4 () | 20 nM |
| in vitro study | dBET1 treatment can down-regulate the expression of MYC and PIM1 without affecting the transcription of BRD4 and BRD3. The transcription of BRD2 and the protein stability of its gene product are affected by dBET1. After 24 hours of treatment, dBET1 can effectively inhibit MV4;11 cell proliferation, IC50 = 0.14 μM. Exposure of cells from primary leukemia patients to dBET1 can cause dose-proportional depletion of BRD4 and induce apoptosis. In LPS-stimulated microglia, dBET1-mediated targeted degradation of the BET protein inhibited the pro-inflammatory response. That is, the depletion of BRD2 and BRD4 caused by dBET1 is related to the significant decrease of COX-2 and iNOS protein levels induced by LPS, and the decrease of transcription levels of pro-inflammatory genes Nos2, Il-1β, Il-6, Tnfα, Ccl2, Ptgs2, Mmp9. |
| in vivo study | inoculated with human MV4; In the mouse model of 11 leukemia cells, the administration of dBET1 attenuates tumor deterioration and reduces tumor weight. Intraperitoneal injection of 50 mg/kg dBET1 to detect its pharmacokinetic properties: 50 mg/kg dose can ensure drug exposure, Cmax = 392 nM, Tmax = 0.5 hr, terminal t 1/2=6.69 hr, AUC last = 2109 hr * ng/ml, AUC INF = 295 hr * ng/ml. DBET1 was well tolerated in mice treated for two weeks, with no significant changes in body weight and no significant changes in white blood cell count, hematocrit or platelet count. |
| use | a CRBN-based BET degrading agent with an IC50 of 20 nM for BRD4 and high selectivity. Among the 7429 detected proteins, only the expression of tumor proteins MYC, PIM1 and BRD2, BRD3 and BRD4 decreased significantly after dBET1. |
Last Update：2024-04-09 19:05:03
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CAS: 1799711-21-9
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Product Name: dBET1 Visit Supplier Webpage Request for quotation
CAS: 1799711-21-9
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
CAS: 1799711-21-9
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
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