GLPG3312

SKU: orb2566175

Description

GLPG3312 is an orally active, potent pan-SIK inhibitor with low nanomolar IC50 values against SIK1, SIK2, and SIK3. It demonstrates anti-inflammatory and immunomodulatory effects in human primary myeloid cells and mouse models, supporting its use in researching inflammatory and autoimmune diseases.

Research Area

Cardiovascular Research, Cell Biology, Signal Transduction, Stem Cell & Developmental Biology

Key Properties

• CAS Number: 2340388-72-7
• MW: 453.44
• Purity: 98.53%
• Formula: C₂₃H₂₁F₂N₅O₃
• SMILES: O=C(NC1CC1)C2=C(OC)C=C(C=C2OC(F)F)N3C=NC=4C=C(C=CC43)C=5C=NN(C5)C
• Target: SIK,Bcr-Abl,LIM Kinase,RIP kinase,Discoidin Domain Receptor (DDR),TGF-beta/Smad,MAPK,Src
• Solubility: DMSO:80 mg/mL (176.43 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:3.3 mg/mL (7.28 mM)

Bioactivity

• Target IC50:
  Monocyte-derived macrophages (MdMs): 34 nM|Primary CD14⁺ monocytes(human): 17 nM
• In Vivo:
  In Balb/c mice, GLPG3312 was administered p.o. at 0.3, 1, or 3 mg/kg, followed by i.p. LPS (100 μg) 15 min later. Plasma cytokines measured at 1.5 h post-LPS showed TNFα inhibition of 27.0%, 57.2%, and 77.5%, respectively, and IL-10 increases of 1.3-, 2.4-, and 3.1-fold at the same doses. GLPG3312 also exhibited favorable PK, with oral bioavailability of 60% in mice, 41.4% in rats (5 mg/kg), and 45.5% in dogs (30 mg/kg), along with low CL and acceptable t₁/₂.
• In Vitro:
  In LPS (100 ng/mL)-stimulated human primary CD14⁺ monocytes and monocyte-derived macrophages (MdMs),GLPG3312 inhibited TNFα release in monocytes(IC₅₀ 17 nM) and in MdMs(IC₅₀ 34 nM). At a concentration of 20 μM, GLPG3312 enhanced IL-10 secretion by 14.8-fold in monocytes and 2.8-fold in MdMs. Cells were preincubated with the compound for 1 hour before LPS stimulation, and cytokine levels were measured at 4 hours for monocytes and at 2 and 20 hours for IL-10 and TNFα, respectively, in MdMs.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

GLPG 3312

Compound Identifiers

PubChem CID

151447433