I-BET151 (GSK1210151A) — OPTICALLY PURE SOURCE

Background Information:

The Bromodomain and Extra Terminal domain (BET), a family of four
proteins that selectively recognize and bind to acetylated lysine
residues in histone, plays a key role in many cellular processes,
including inflammatory gene expression, mitosis, and viral/host
interaction by controlling the assembly of histone acetylation-dependent
chromatin complexes. BET proteins stimulate transcription by recruiting
specific types of proteins, for example the super elongation complex
(SEC), to chromatin, leading to stimulation of transcriptional
elongation of certain target genes including oncogenes and
pro-inflammatory cytokines. Targeting BET proteins and displacing them
could provide a method of inducing cell cycle arrest and even cell death
of defectively programmed cells. I-BET151, a small molecule inhibitor
that interacts with BRD4 and BRD3 BET proteins and displaces them from
chromatin, has profound efficacy against human and murine MLL-fusion
leukemic cell lines, through the induction of early cell cycle arrest
and apoptosis. The mode of action is, at least in part, due to
suppressing the transcription of key genes (BCL2, C-MYC and CDK6) that
are critical for MLL-fusion leukemia maintenance (Ref. 1).

Reference:

1. M. A. Dawson, et al, Inhibition of BET recruitment to chromatin as
an effective treatment for MLL-fusion leukaemia, Nature, 478,
529–533(27 October 2011).
2. All pharmacological parameters of this compound (I-BET151) are based
on a single isomer (optically pure R-enantiomer), thus a compound with
adequate optical purity (confirmed by Chiral HPLC) is required for an
uncompromised high quality research. Buyer Beware: Partially racemized
I-BET151 (up to 15% wrong isomer, thus give the optical purity as low as
85%), is being offered by many other vendors, who won’t report their
optical purity (too poor to report).

APIM050333: I-BET151 (GSK1210151A) — OPTICALLY PURE SOURCE

CAS No.: 1300031-49-5.
Molecular Formula: C₂₃H₂₁N₅O_3.
Molecular Weight: 415.4.
Purity: >99.5% (achiral HPLC at 214 and 254 nm), 100% optical purity (chiral HPLC).
QC: HPLC-MS, ¹HNMR, Chiral HPLC, and Quantitative Elemental Analysis.
Solubility: Soluble in DMSO.
Storage: Store at 0°C (short term), -20°C (long term), desiccated.