dBET6

dBET6 is a novel degrader of BET bromodomain proteins. dBET6 prompts a collapse of global elongation that phenocopies CDK9 inhibition.

Product information

CAS Number: 1950634-92-0

Molecular Weight: 841.37

Formula: C42H45ClN8O7S

Synonym:

d-BET6

dBET6

d BET6

Chemical Name: 2-((S)-4-(4-Chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)-N-(8-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetamido)octyl)-acetamide

Smiles: CC1C2=C(SC=1C)N1C(=NN=C1C)[C@H](CC(=O)NCCCCCCCCNC(=O)COC1=CC=CC3=C1C(=O)N(C1CCC(=O)NC1=O)C3=O)N=C2C1C=CC(Cl)=CC=1

InChiKey: JGQPZPLJOBHHBK-UFXYQILXSA-N

InChi: InChI=1S/C42H45ClN8O7S/c1-23-24(2)59-42-35(23)37(26-13-15-27(43)16-14-26)46-29(38-49-48-25(3)50(38)42)21-33(53)44-19-8-6-4-5-7-9-20-45-34(54)22-58-31-12-10-11-28-36(31)41(57)51(40(28)56)30-17-18-32(52)47-39(30)55/h10-16,29-30H,4-9,17-22H2,1-3H3,(H,44,53)(H,45,54)(H,47,52,55)/t29-,30?/m0/s1

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO: 100 mg/mL(118.85 mM).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

dBET6 is a highly cell-permeable degrader of BET bromodomains. It is potent in most cancer cell lines. dBET6 features highly increased cellular potency with evident degradation in the sub-nanomolar range. Treatment with 100 nM dBET6 leads to degradation of BRD4 after 1 hr, prompting subsequent downregulation of c-MYC and induction of apoptosis. dBET6 disrupts global productive transcription elongation. dBET6 treatment leads to a widespread decrease in steady-state mRNA levels, but observed an incommensurate impact on expression of members of the core regulatory circuitry of leukemogenic transcription factors. The collapse of the core transcriptional machinery prompted by BET degradation precedes a robust apoptotic response, of apparent translational significance.

In Vivo:

dBET6 is well tolerated. Upon dBET6 treatment, a significant reduction of leukemic burden is observed in a disseminated mouse model of T-ALL. Moreover, mice treated with dBET6 (7.5 mg/kg BID) exhibits a significant survival benefit compared to mice treated with vehicle control or JQ1 (20 mg/kg QD).

References:

1. Winter GE, et al. Mol Cell. 2017, 67(1):5-18.e19.

Products are for research use only. Not for human use.