BIX 02565

SKU: orb1689888

Description

BIX 02565 is a highly potent and selective small molecule inhibitor of ribosomal S6 kinase 2 (RSK2), exhibiting an IC50 of 1.1 nM. This compound is a valuable research tool for investigating RSK2 signaling in cellular models of cancer and neurological disorders, with utility demonstrated in both in vitro and in vivo experimental systems.

Research Area

Cell Biology, Signal Transduction

Key Properties

• CAS Number: 1311367-27-7
• MW: 458.56
• Purity: 99.61%
• Formula: C₂₆H₃₀N₆O₂
• SMILES: C[C@@H]1CCNC(=O)c2cc3ccc(cc3n12)C(=O)Nc1nc2ccccc2n1CCCN(C)C
• Target: LRRK2,S6 Kinase
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:1 mg/mL (2.18 mM);DMSO:20 mg/mL (43.61 mM)

Bioactivity

• Target IC50:
  PRKD1:35 nM (cell free)|RSK2:1.1 nM (cell free)|LRRK2:16 nM (cell free)
• In Vivo:
  Infusion of BIX 02565 (1, 3, and 10 mg/kg) in the rat CV screen resulted in a precipitous decrease in both mean arterial pressure (MAP; to -65 ± 6 mm Hg below baseline) and heart rate (-93 ± 13 beats/min). In telemetry-instrumented rats, BIX 02565 (30, 100, and 300 mg/kg p.o. QD for 4 days) elicited concentration-dependent decreases in MAP after each dose (to -39 ± 4 mm Hg on day 4 at T(max)); analysis by Demming regression demonstrated strong correlation independent of route of administration and influence of anesthesia .
• In Vitro:
  BIX 02565 inhibited RSK2 with IC50 value of 1.1 nM. It also inhibited LRRK2 and PRKD1 with IC50 values of 16 and 35 nM . BIX 02565 elicited >50% inhibition at adrenergic α1A-, α1B-, α1D-, α2A-, β2-, and imidazoline I2 receptors (IC50s: 0.052-1.820 μM) .
• Cell Research:
  A monolayer of exponentially growing HLR-CREB cells was prepared and transfected using Effectene with RSK2. Cells were plated into 96-well culture plates, and compounds were added 20 to 24 h after transfection. Luciferase expression (48 h) and activity (5 min) were determined using Steady-Glo per manufacturer's instructions, and results were represented as the percentage luciferase activity relative to the control measured in the absence of inhibitors (percentage of control); the IC50 was fitted to a standard four-parameter logistic equation. Each data point represents an average of triplicate observations .
• Animal Research:
  Mean arterial pressure was assessed in conscious, freely moving male Sprague-Dawley rats (n = 6/group) instrumented with telemetry transmitters similar to that described previously. BIX 02565 (30, 100, and 300 mg/kg p.o. QD) was administered as a solution (10 ml/kg) in a 20% hydroxy-propyl-β-cyclodextran vehicle as described previously. Mean arterial pressure was reported from 2 h before (baseline) and 90 h after the first dose; compound was administered at 0, 24, 48, and 72 h. A blood sample was collected from satellite rats (n = 3/group) at 1-h after dose (Tmax) on days 1 and 4 for analysis of plasma drug concentrations by mass spectrometry .

Storage & Handling

• Storage: store at low temperature,keep away from moisture | Pure form: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

RSK2, S6Kinase, S6K, S6 Kinase, Ribosomal S6 Kinase (RSK), BIX02565, BIX-02565, BIX 02565, inhibit, Inhibitor, LRRK2

Compound Identifiers

PubChem CID

53246941