SMALL MOLECULES
Contributor Information
- Name Steve Wedge
Tool Details
- Tool name: Extracellular signal-related protein kinase 5 ERK5 Small Molecule (Collaborative Toolkit)
- Tool type: Small molecules
- Tool sub-type: Inhibitor
- Purpose: Inhibitor
- Cancer type: Breast cancer; Genitourinary cancer; Liver cancer
- Molecular weight of the target: A potent inhibitor of ERK5 in enzyme (IC50 = 79 nM) and whole cell (IC50 =970 nM) assays.
- Description: An inhibitor of extracellular signal-related protein kinase 5 (ERK5). Mitogen/extracellular signal regulated kinase kinase-5 (MEK5) specifically activates ERK5, also known as Big MAP kinase 1 (BMK1). The MEK5/ERK5 pathway is activated by EGF and is required for EGF-induced proliferation and connexin 43 gap junction communication in certain cellular contexts. ERK5 is comprised of 815 amino acids with a unique C-terminal tail containing a myocyte enhancer factor 2 (MEF2)-interacting domain and a potent transcriptional activation domain. ERK5 regulates several transcriptional factors such as MEF2C, c-Fos, Fra-1, Sap-1, cMyc and NFÎşB. ERK5 activation has a potential role in tumorigenesis and is implicated in breast, prostate and hepatic cancer. ERK5 also plays a key role in embryogenesis; ERK5 knock-out embryos die between day 9.5 and 11.5 due to a loss of vascular integrity.
- Selectivity: Tested in the DiscoveRx panel of 456 kinases at a concentration of 10 ÎźM. Seventeen kinases were inhibited by >99% at this concentration, including ERK5, and the S(35) selectivity score ((number of non-mutant kinases with % of control <35)/(number of non-mutant kinases tested)) was 0.205. Ten representative kinases were selected for Kd determinations and the three most sensitive kinases were CSF1R (46nM), DCAMKL1 (61 nM) and ERK5 (180 nM).
- IC50: A potent inhibitor of ERK5 in enzyme (IC50 = 79 nM) and whole cell (IC50 =970 nM) assays.
- Additional notes: Tested in vitro and in vivo.
- For Research Use Only
Target Details
- Target molecular weight: A potent inhibitor of ERK5 in enzyme (IC50 = 79 nM) and whole cell (IC50 =970 nM) assays.
- Primary target: ERK5
Application Details
- Application notes: Tested in vitro and in vivo. Cell permeability: Caco2 Papp A2B/B2A (Efflux ratio) = 27/26 (0.94)
Handling
- Purity: 381 kDa
- Solubility: 100ÎźM
Documentation
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