ARN-3236

SKU: orb1301364

Description

ARN-3236 is a potent, orally bioavailable, and selective salt-inducible kinase 2 (SIK2) inhibitor, with IC50 values of <1 nM, 21.63 nM, and 6.63 nM for SIK2, SIK1, and SIK3, respectively. This small molecule exhibits anti-cancer activity and is a valuable research tool for studying SIK2 signaling in both in vitro cellular assays and in vivo cancer models.

Research Area

Epigenetics & Chromatin, Signal Transduction

Key Properties

• CAS Number: 1613710-01-2
• MW: 336.41
• Purity: 99.57%
• Formula: C₁₉H₁₆N₂O₂S
• SMILES: COc1ccc(-c2c[nH]c3nccc(-c4ccsc4)c23)c(OC)c1
• Target: SIK,AMPK
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:4 mg/mL (11.89 mM);DMSO:130 mg/mL (386.43 mM)

Bioactivity

• Target IC50:
  SIK3:6.63 nM|SIK2 < nM |SIK1:21.63 nM
• In Vitro:
  Salt-inducible kinase 2 (SIK2) is overexpressed in approximately 30% of high-grade serous ovarian cancers. ARN-3236 inhibite the growth of 10 ovarian cancer cell lines at an IC50 of 0.8 to 2.6 μMol/L, wher the IC50 of ARN-3236 was inversely correlated with endogenous SIK2 expression (Pearson r = -0.642, P = 0.03). ARN-3236 enhanced sensitivity to paclitaxel in 8 of 10 cell lines, as well as in SKOv3ip (P = 0.028) and OVCAR8 xenografts. In at least three cell lines, a synergistic interaction was observed. ARN-3236 uncouple the centrosome fro the nucleus in interphase, blocked centrosome separation in mitosis, caused prometaphase arrest, and induced apoptotic cell death and tetraploidy. ARN-3236 also inhibited AKT phosphorylation and attenuated survivin expression.
• Cell Research:
  SIK2 expression was determined in ovarian cancer tissue Samples and cell lines. ARN-3236 was tested for its efficiency to inhibit growth and enhance paclitaxel sensitivity in cultures and xenografts of ovarian cancer cell lines. SIK2 siRNA and ARN-3236 were compared for their ability to produce nuclear-centrosome dissociation, inhibit centrosome splitting, block mitotic progression, induce tetraploidy, trigger apoptotic cell death and reduce AKT/survivin signaling.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Disclaimer: For research use only

Alternative Names

ARN3236, ARN-3236, ARN 3236, inhibit, Inhibitor, Salt-inducible Kinase (SIK), SIK2

Compound Identifiers

PubChem CID

74766530