ARN-3236 Chemical Properties

Density 

1.278±0.06 g/cm3(Predicted)

storage temp. 

Store at -20°C

solubility 

DMSO:65.67(Max Conc. mg/mL);195.21(Max Conc. mM)
Ethanol:2.0(Max Conc. mg/mL);5.95(Max Conc. mM)
DMF:30.0(Max Conc. mg/mL);89.18(Max Conc. mM)
DMSO:PBS (pH 7.2) (1:4):0.2(Max Conc. mg/mL);0.59(Max Conc. mM)

form 

A crystalline solid

pka

13.33±0.40(Predicted)

color 

White to off-white

ARN-3236 Usage And Synthesis

Uses

ARN-3236 is an oral active and selective inhibitor of salt-inducible kinase 2 (SIK2), with IC50s of <1 nM, 21.63 nM and 6.63 nM for SIK2, SIK1 and SIK3, respectively. Has anti-cancer activity[1][2].

Biological Activity

ARN-3236 is an orally active, ATP-competitive, SIK2-selective salt-inducible kinase inhibitor (IC50 = 21.63 nM/SIK1, <1 nM/SIK2, 6.63 nM/SIK3) th at suppresses cellular SIK2 activity (by 58% at 1 μM; SKOv3-SIK2 cells, 48 h) with high selectivity over >456 kinases. ARN-3236 effectively suppresses SIK2-dependent growth of ovarian cancer cultures (IC50 = 0.8-2.6 μM in 10 lines, 72 h) and in murine xenograft models in vivo (30, 60, 100 mg/kg/day p.o.). In addition, ARN-3236 sensitizes ovarian cancer cells to paclitaxel in vitro and in vivo. ARN-3236 completes the SIK1-selective HG-9-91-01 (SIK1/2/3 IC50 = 0.6/6.6/9.6 nM) in probing SIKs-mediated cellular signaling events.

in vivo

IC 50

SIK2: <1 nM (IC₅₀); SIK1: 21.63 nM (IC₅₀); SIK3: 6.63 nM (IC₅₀)

storage

Store at -20°C

References

[1] Lombardi MS, et al. SIK inhibition in human myeloid cells modulates TLR and IL-1R signaling and induces an anti-inflammatory phenotype. J Leukoc Biol. 2016 May;99(5):711-21. DOI:10.1189/jlb.2A0715-307R
[2] Zhou J, et al. A Novel Compound ARN-3236 Inhibits Salt-Inducible Kinase 2 and Sensitizes Ovarian Cancer Cell Lines and Xenografts. Clin Cancer Res. 2017 Apr 15;23(8):1945-1954. DOI:10.1158/1078-0432.CCR-16-1562