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dBET1 PROTAC chemical

Cat.No.S8296

dBET1 is a CRBN-based BET degrader with an IC50 of 20 nM, showing highly selectivity. Out of 7,429 proteins, only the expression of the oncoproteins MYC and PIM1, as well as BRD2, BRD3 and BRD4 are significantly downregulated by this compound treatment.
dBET1 PROTAC chemical Chemical Structure

Chemical Structure

Molecular Weight: 785.27

Jump to Mechanism of Action Solubility Chemical Information, Storage & Stability

Quality Control

Batch: S829601 DMSO]100 mg/mL]false]Ethanol]39 mg/mL]false]Water]˂1 mg/mL]false Purity: 99.64%
99.64

Chemical Information, Storage & Stability

Molecular Weight 785.27 Formula

C38H37ClN8O7S

 Storage (From the date of receipt) 3 years -20°C powder
CAS No. 1799711-21-9 -- Storage of Stock Solutions

Synonyms N/A Smiles CC1=C(SC2=C1C(=NC(C3=NN=C(N32)C)CC(=O)NCCCCNC(=O)COC4=CC=CC5=C4C(=O)N(C5=O)C6CCC(=O)NC6=O)C7=CC=C(C=C7)Cl)C

Solubility

In vitro
Batch:

DMSO : 100 mg/mL (127.34 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 39 mg/mL

Water : ˂1 mg/mL

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Mass Concentration Volume Molecular Weight

In vivo
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Mechanism of Action

Targets/IC50/Ki
BRD4 [1]
20 nM
In vitro

Treatment with dBET1 elicits a comparable, modest effect on MYC and PIM1 expression. Its treatment downregulates MYC and PIM1 transcription, suggestive of secondary transcriptional effects and transcription of BRD4 and BRD3 are unaffected, consistent with post-transcriptional effects. Transcription of BRD2 is affected by this compound and protein stability of the BRD2 gene product is influenced by it. This chemical induces a potent and superior inhibitory effect on MV4;11 cell proliferation at 24 hours (measured by ATP content, IC50 = 0.14 μM). Exposure of primary leukemic patient blasts to this compound elicits dose-proportionate depletion of BRD4 and induction of apoptosis[1]. This compound-mediated targeted degradation of BET proteins robustly dampens pro-inflammatory responses in LPS-stimulated microglia, that is, depletion of BRD2 and BRD4 with it is associated with dramatically reduced LPS-induced COX-2 and iNOS protein levels and pro-inflammatory gene transcription of Nos2, Il-1β, Il-6, Tnfα, Ccl2, Ptgs2, and Mmp9[2].
In vivo

Administration of dBET1 attenuates tumor progression and decreases tumor weight assessed post-mortem in murine xenograft model of human MV4;11 leukemia cells. Pharmacokinetic studies of this compound (50 mg/kg IP) corroborate adequate drug exposure in vivo (Cmax = 392 nM, Tmax=0.5 hr, terminal t1/2=6.69 hr, AUClast=2109 hr*ng/ml, AUCINF=295 hr*ng/ml). Two weeks of this chemical is well tolerated by mice without a meaningful effect on weight, white blood count, hematocrit or platelet count[1].
References

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