AU1

Research use only, not for human use.

AU1 (GSK 1379725A) is the first selective small molecule inhibitor of BPTF bromodomain (bromodomain PHD finger transcription factor) with Kd of 2.8 uM in a cell-based reporter assay.

AU1 (GSK 1379725A) is the first selective small molecule inhibitor of BPTF bromodomain (bromodomain PHD finger transcription factor) with Kd of 2.8 uM in a cell-based reporter assay, shows no binding activity for Brd4; interferes with its regulatory activity in cultured cells.

From the NMR titration of GSK1379725A, the bound and unbound resonances are separated by 171 Hz, providing an upper bound for the chemical exchange rate. Assuming an association rate of 1×108 M-1 s-1 as a high end for a range of protein-small molecule interactions, (e.g., chymotrypsin: proflavin k1=1.2×108 M-1 s-1), an upper Kd of 8 μM is estimated from this experiment. For a more accurate determination with a non-fluorinated protein, ITC is used as a complementary direct binding assay using unlabeled BPTF. A Kd of 2.8 μM is obtained, consistent with our intermediate exchange resonance broadening by PrOF NMR. Although GSK1379725A has been demonstrated to be selective over Brd4, a full selectivity panel against other bromodomains will be needed. A database search using ChEMBL only showed GSK1379725A to be active in five cellular assays with an EC50 of 500 nM carried out. Additionally, no kinase activity has been reported for GSK1379725A despite the growing screening use of the PKIS library.

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GSK 1379725A

Chromatin/Epigenetic

Bromodomain

Bromodomain

Other Indications

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1802251-00-8

450.47

C23H23FN6O3

>98% (HPLC)

In Vitro:?DMSO : 100 mg/mL (221.99 mM)

O=C(OC)C1=CC=CC(NC(NC2CN(C3=NC(NC4=CC=C(F)C=C4)=NC=C3)CC2)=O)=C1

Benzoic acid, 3-[[[[1-[2-[(4-fluorophenyl)amino]-4-pyrimidinyl]-3-pyrrolidinyl]amino]carbonyl]amino]-, methyl ester

(-20℃)

With Ice Pack

≥ 2 years