BRD-7389

BRD7389 is a specific RSK family kinase inhibitor with IC50s of 1.5 μM, 2.4 μM, and 1.2 μM for RSK1, RSK2, and RSK3, respectively. BRD7389 is a small-molecule inducer of insulin expression in pancreatic α-cells[1].

Research Areas >> Metabolic Disease

Signaling Pathways >> MAPK/ERK Pathway >> Ribosomal S6 Kinase (RSK)

RSK1:1.5 μM (IC50)

RSK2:2.4 μM (IC50)

RSK3:1.2 μM (IC50)

CDK5/p35:6.5 μM (IC50)

DRAK1:2.8 μM (IC50)

FLT3:3.5 μM (IC50)

PIM1:3.7 μM (IC50)

PKG1α:6.5 μM (IC50)

SGK:13.8 μM (IC50)

BRD7389 (0.425-6.8 μM) induces insulin expression in mouse α-cells after 3 days treatment. BRD7389 induces a dose-dependent up-regulation of insulin (Ins2) mRNA, peaking at 0.85 μM; 5 days treatment with BRD7389 results in greater induction of insulin gene expression, about 50-fold at 0.85 μM[1]. BRD7389 (0.85-6.8μM) significantly up-regulates Pdx1 mRNA expression in mouse α-cell line[1]. BRD7389 also increases β-cell-specific gene expression in primary human islet cells[1]. BRD7389 (1 μM; added 30 min prior to Carbachol treatment 48 h) fully abolishes carbachols timulated cell proliferation, but has little effect on the basal level of proliferation[2]. RT-PCR[1] Cell Line: Mouse α-cell line Concentration: 0.425, 0.85, 1.7, 3.4, 6.8 μM Incubation Time: 3 days and 5 days Result: Up-regulated expression of Pdx1. Cell Proliferation Assay[2] Cell Line: SNU-407 colon cancer cell Concentration: 1 μM Incubation Time: Added 30 min prior to Carbachol treatment (48 h) Result: Almost completely blocked Carbachol (1 mM)-stimulated cell proliferation.

[1]. Fomina-Yadlin D, et al. Small-molecule inducers of insulin expression in pancreatic alpha-cells. Proc Natl Acad Sci U S A. 2010 Aug 24;107(34):15099-104.

[2]. Park YS, et al. EGFR and PKC are involved in the activation of ERK1/2 and p90 RSK and the subsequent proliferation of SNU-407 colon cancer cells by muscarinic acetylcholine receptors. Mol Cell Biochem. 2012 Nov;370(1-2):191-8.