| Identification | Back Directory | [Name]
1H-Inden-1-one, 2,3-dihydro-4,6-dimethoxy-3-(4-methoxyphenyl)-, (3R)- | [CAS]
2767124-77-4 | [Synonyms]
(R)-STU104 1H-Inden-1-one, 2,3-dihydro-4,6-dimethoxy-3-(4-methoxyphenyl)-, (3R)- | [Molecular Formula]
C18H18O4 | [MOL File]
2767124-77-4.mol | [Molecular Weight]
298.33 |
| Hazard Information | Back Directory | [Uses]
(R)-STU104 is a potent and orally active TAK1-MKK3 interaction inhibitor with IC50s of 0.58 μM and 4.0 μM for TNF-α and MKK3 phosphorylation. (R)-STU104 suppresses the TAK1/MKK3/p38/MnK1/MK2/elF4E signal pathways through binding with MKK3 and disrupting the TAK1 phosphorylating MKK3. (R)-STU104 can be used for researching ulcerative colitis[1]. | [in vivo]
(R)-STU104 (1, 3 and 10 mg/kg; IG for 7 days) ameliorates the symptoms of DSS-induced experimental colitis in mice, and significantly inhibits inflammatory cytokine protein[1]. Pharmacokinetic Parameters of (R)-STU104 in male C57 mice[1].
| IV (5 mg/kg) | PO (30 mg/kg) | | Tmax (h) | | 0.083 | | AUC0-t (μg/L·h) | 7249 | 9895 | | AUC0-∞ (μg/L·h) | 8635 | 16991 | | MRT0-∞ (h) | 7.32 | 12.52 | | Cmax (ng/mL) | 2920 | 2290 | | t1/2 (ng/mL) | 9.29 | 8.67 | | VZ (L/kg) | 7.76 | 3.68 | | CLZ (ng/mL) | 0.58 | 0.29 | | F (%) | 33% | |
| Animal Model: | C57BL/6 mice (dextran sodium sulfate (DSS)-induced acute ulcerative colitis)[1] | | Dosage: | 1, 3 and 10 mg/kg | | Administration: | IG, for 7 days | | Result: | Ameliorated the symptoms of DSS-induced experimental colitis, and significantly inhibited inflammatory cytokine protein TNF-α, IL-1β, IL-6, and IL-23. |
| [References]
[1] Tang ML, et al. Discovery of First-in-Class TAK1-MKK3 Protein-Protein Interaction (PPI) Inhibitor (R)-STU104 for the Treatment of Ulcerative Colitis through Modulating TNF-α Production. J Med Chem. 2022 May 12;65(9):6690-6709. DOI:10.1021/acs.jmedchem.1c02198 |
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