BIX02189 is a potent and selective inhibitor of MEK5 and ERK5(IC50 : 1.5 nM and 59 nM).

98%

Store at -20℃ for one year（Powder）；Store at 2-4℃ for two weeks；Store at -20℃ for six months after dissolution.

DMSO:49.4 mg/mL (112.14 mM)

RPS6KA6 (RSK4):990 nM, ERK5:59 nM, Kit:1.1 μM, RPS6KA3 (RSK2):2.1 μM, CSF1R (FMS):46 nM, Abl1:2.4 μM, FGFR1:1 μM, JAK3:440 nM, TGFβR1:580 nM, Lck:250 nM, MEK5:1.5 nM

BIX02189, which inhibited catalytic function of purified, MEK5 enzyme.?The MEK5 inhibitors blocked phosphorylation of ERK5, without affecting phosphorylation of ERK1/2 in sorbitol-stimulated HeLa cells.?The compounds also inhibited transcriptional activation of MEF2C, a downstream substrate of the MEK5/ERK5 signaling cascade, in a cellular trans-reporter assay system[1].

BIX02189 is a selective inhibitor of MEK5 with IC50 of 1.5 nM.

98%

Store at -20℃ for one year（Powder）；Store at 2-4℃ for two weeks；Store at -20℃ for six months after dissolution.

DMSO:56 mg/mL (127.1 mM),H2O:<1 mg>

MEK5:1.5 nM

用BIX02189预处理以剂量依赖性方式抑制山梨醇诱导的HeLa细胞中ERK5的磷酸化,并且对ERK1/2,p38和JNK1/2 MAPKs的磷酸化没有抑制活性。在HeLa或HEK293细胞中仅用BIX02189处理24小时不显示任何细胞毒性作用。BIX02189抑制HeLa和HEK293细胞中MEK5/ERK5/MEF2C驱动的萤光素酶表达,IC50分别为 0.53 μM和0.26 μM。BIX02189抑制MEK5和ERK5催化活性,IC50分别为1.5 nM和59 nM。BIX02189抑制CSF1R(FMS),IC50为46 nM,但对相关激酶MEK1,MEK2,ERK1,p38α,JNK2,EGFR和STK16无活性,IC50 >3.7 μM。BIX02189增强山梨醇诱导的NRCM细胞凋亡,证实了ERK5在心肌细胞中的保护作用。BIX02189（10 μM）抑制ERK5磷酸化,并降低由异丙肾上腺素刺激的新生大鼠心肌细胞（NRCMs）中的肌细胞增强因子2（MEF2）转录活性。

BIX02189 is a selective inhibitor of MEK5 with IC50 of 1.5 nM, also inhibits ERK5 catalytic activity with IC50 of 59 nM in cell-free assays, and does not inhibit closely related kinases MEK1, MEK2, ERK2, and JNK2.

＞98%

Store at -20℃ for one year（Powder）；Store at 2-4℃ for two weeks；Store at -20℃ for six months after dissolution.

BIX 02189；BIX-02189

powder

DMSO : 56 mg/mL (127.1 mM)

Ethanol : 74 mg/mL (168 mM)

MEK5,ERK5

BIX02189 blocks MEK5 and ERK5 catalytic activity with IC50 values of 1.5 nM and 59 nM, respectively. They are more potent than the effect caused by BIX02188 with IC50 values of 4.3 nM and 810 nM, respectively. BIX02189 shows inhibitory activity against CSF1R (FMS) with IC50 of 46 nM but displays no activity against related kinases MEK1, MEK2, ERK1, p38α, JNK2, EGFR, and STK16 with IC50 values of >3.7 μM. Pretreatment with BIX02189 inhibits sorbitol-induced phosphorylation of ERK5 in HeLa cells in a dose dependent manner, and displays no inhibitory activity against the phosphorylation of ERK1/2, p38, and JNK1/2 MAPKs. Treatment with only BIX02189 for 24 hours in HeLa or HEK293 cells does not show any cytotoxic effect. BIX02189 inhibits MEK5/ERK5/MEF2C-driven luciferase expression in HeLa and HEK293 cells with IC50 values of 0.53 μM and 0.26 μM, respectively. This is a more significant than the effect caused by BIX02188. BIX02189 inhibits the activation of ERK5, and suppresses C-terminus of Hsc70-interacting protein (CHIP) mediated p53 ubiquitination, leading to the reverse of the protective effect caused by laminar flow (L-flow) in human umbilical vein endothelial cells (HUVECs) exposed to 15d-PGJ2. BIX02189 (10 uM) inhibits ERK5 phosphorylation, and reduces myocyte enhancer factor 2 (MEF2) transcriptional activity in neonatal rat cardiomyocytes (NRCMs) stimulated by isoproterenol. BIX02189 enhances the sorbitol induced apoptosis in NRCMs, confirming the protective role of ERK5 in cardiomyocytes.

1. Tatake RJ, et al. Biochem Biophys Res Commun, 2008, 377(1), 120-125.

2. Lim JH, et al. Anat Cell Biol, 2011, 44(4), 265-273.

BIX 02565 is a novel ribosomal S6 kinase 2 (RSK2) inhibitor with an IC50 of 1.1 nM.

>98%

Store at -20℃ for one year（Powder）；Store at 2-4℃ for two weeks；Store at -20℃ for six months after dissolution.

BIX-02565;BIX02565

Powder

Ribosomal S6 Kinase (RSK)

BIX 02565, a potent RSK2 inhibitor (IC50=1.1 nM) targets for the treatment of heart failure secondary to myocardial infarction through indirect NHE inhibition. BIX 02565, a second Rsk inhibitor, protects enzyme active sites from reaction with biotinylated nucleotide acyl phosphates.

In telemetry-instrumented rats, BIX 02565 (30, 100, and 300 mg/kg p.o. QD for 4 days) elicits concentration-dependent decreases in MAP after each dose (to -39±4 mm Hg on day 4 at Tmax). BIX 02565 produces concentration-dependent relaxation ex vivo in the phenylephrine-constricted rat aortic ring at concentrations above 0.03 μM with a calculated EC50 of 3.1 μM. Subsequently, BIX 02565 is infused in the anesthetized rat in a low-dose (0.1, 0.3, and 1.0 mg/kg per 20 min) and high-dose (1.0, 3.0, and 10.0 mg/kg per 20 min) series of continuous infusions to test the effect of compound on hemodynamics in vivo.