| Identification | Back Directory | [Name]
4-Methyl-5-[[3-methyl-7-[[6-(4-morpholinyl)-3-pyridazinyl]amino]-3H-imidazo[4,5-b]pyridin-5-yl]oxy]-2-pyridinecarbonitrile | [CAS]
2308520-97-8 | [Synonyms]
GLPG3667
4-Methyl-5-[[3-methyl-7-[[6-(4-morpholinyl)-3-pyridazinyl]amino]-3H-imidazo[4,5-b]pyridin-5-yl]oxy]-2-pyridinecarbonitrile | [Molecular Formula]
C22H21N9O2 | [MOL File]
2308520-97-8.mol | [Molecular Weight]
443.46 |
| Chemical Properties | Back Directory | [Boiling point ]
791.6±70.0 °C(Predicted) | [density ]
1.46±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted) | [form ]
Solid | [pka]
4.72±0.10(Predicted) | [color ]
Off-white to light yellow |
| Hazard Information | Back Directory | [Uses]
GLPG3667 is a reversible, ATP-competitive and orally active TYK2 inhibitor with an IC50 of 2.3 nM. GLPG3667 inhibits IFNα/pSTAT1, and the IC50 values ??in human peripheral blood mononuclear cell (PBMC) and whole blood assays are 70 nM and 623 nM, respectively. GLPG3667 has the potential for the study of inflammatory and autoimmune diseases[1]. | [in vivo]
GLPG3667 (3-30 mg/kg; oral administration, once daily (q.d.); for 5 days) reduces dermal ear inflammation in an IL-23-induced in vivo mouse model of psoriasis[1]. | Animal Model: | Female BALB/c mice (IL-23-induced psoriasis model)[1] | | Dosage: | 3, 10, and 30 mg/kg (Solutol HS15/methyl cellulose 0.5% (2/98; v/v)) | | Administration: | Oral administration, once daily (q.d.); for 5 days | | Result: | Successfully reduced ear pinna thickening and STAT3 phosphorylation in the epidermis and dermis. Additionally, reduced neutrophil infiltration in the dermis. However, there was no clear dose-response relationship observed, likely due to other pathways not impacted by TYK2 inhibition. |
| [IC 50]
Tyk2: 2.3 nM (IC50); JAK1: 38 nM (IC50); JAK2: 7.3 nM (IC50); JAK3: 374 nM (IC50) | [References]
[1] Mammoliti O, et al. Discovery of GLPG3667, a Selective ATP Competitive Tyrosine Kinase 2 Inhibitor for the Treatment of Autoimmune Diseases. J Med Chem. 2024 Jun 13;67(11):8545-8568. DOI:10.1021/acs.jmedchem.4c00769 |
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