dBET1

SKU: orb1225894

Description

dBET1 is a proteolysis-targeting chimera (PROTAC) molecule that appendes a competitive antagonist of BET bromodomain (JQ1) to a phthalimide moiety to hijack the cereblon E3 ubiquitin ligase complex; induces highly selective cereblon-dependent BET protein degradation in vitro (EC50=430 nM) and in vivo and delayed leukemia progression in mice.

Key Properties

• CAS Number: 1799711-21-9
• MW: 785.273
• Purity: >98% (HPLC)
• Formula: C₃₈H₃₇ClN₈O₇S
• SMILES: CC(N(C1C2=NN=C(C)N2C3=C(C(C)=C(C)S3)C(C4=CC=C(Cl)C=C4)=N1)CCCCNC(COC5=CC=CC(C(N6C(CC7)C(NC7=O)=O)=O)=C5C6=O)=O)=O
• Target: PROTAC
• Solubility: DMSO: 50 mg/mL; Water: Insoluble; Ethanol: 5 mg/mL （ < 1 mg/ml refers to the product slightly soluble or insoluble )

Bioactivity

• In Vivo:
  Administration of dBET1 attenuates tumor progression as determined by serial volumetric measurement, and decreases tumor weight assessed post-mortem. Acute pharmacodynamic degradation of BRD4 is observed four hours after a first or second daily treatment with dBET1 (50 mg/kg IP). A statistically significant destabilization of BRD4, down regulation of MYC and inhibition of proliferation is observed with dBET1 compared with vehicle control in excised tumors. Two weeks of dBET1 is well tolerated by mice without a meaningful effect on weight, white blood count, hematocrit or platelet count.
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• In Vitro:
  Treatment with dBET1 down regulates MYC and PIM1 transcription. Degradation of BRD4 by dBET1 is associated with a more potent apoptotic consequence in MV4; 11 cell line. Significantly increased apoptosis after only 4 h of dBET1 treatment is enhanced at 8 h. dBET1 also induces a potent and superior inhibitory effect on MV4; 11 cell proliferation at 24 hours (measured by ATP content, IC50 = 0.14 μM, compare to IC50 = 1.1 μM with JQ1).
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Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

dBET 1

Quick Database Links

Gene Symbol

PROTAC