| Identification | Back Directory | [Name]
ARN-3236 | [CAS]
1613710-01-2 | [Synonyms]
ARN-3236
ARN-3236; ARN 3236; ARN3236
3-(2,4-Dimethoxyphenyl)-4-(3-thienyl)-1H-pyrrolo[2,3-b]pyridine
1H-Pyrrolo[2,3-b]pyridine, 3-(2,4-dimethoxyphenyl)-4-(3-thienyl)-
3-(2,4-DIMETHOXYPHENYL)-4-(THIOPHEN-3-YL)-1H-PYRROLO[2,3-B]PYRIDINE | [Molecular Formula]
C19H16N2O2S | [MDL Number]
MFCD31813721 | [MOL File]
1613710-01-2.mol | [Molecular Weight]
336.41 |
| Chemical Properties | Back Directory | [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 |
| Hazard Information | Back Directory | [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 activeATP-competitiveSIK2-selective salt-inducible kinase inhibitor (IC50 = 21.63 nM/SIK1<1 nM/SIK26.63 nM/SIK3) th at suppresses cellular SIK2 activity (by 58% at 1 μM; SKOv3-SIK2 cells48 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 lines72 h) and in murine xenograft models in vivo (3060100 mg/kg/day p.o.). In additionARN-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]
ARN-3236 (60 mg/kg, orally) sensitizes ovarian cancer to NSC 125973 in vivo[2]. | Animal Model: | SKOv3ip-bearing mice and OVCAR8-bearing mice[2]. | | Dosage: | 60 mg/kg. | | Administration: | Orally once daily for 3 weeks (SKOv3ip-bearing mice) and 4 weeks (OVCAR8-bearing mice). | | Result: | Sensitized ovarian cancer to NSC 125973. |
| [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 |
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