| Identification | Back Directory | [Name]
TAK-828F | [CAS]
1854901-94-2 | [Synonyms]
TAK-828F
Cyclobutaneacetic acid, 3-[[(5R)-5-[[(7-fluoro-2,3-dihydro-1,1-dimethyl-1H-inden-5-yl)amino]carbonyl]-7,8-dihydro-2-methoxy-1,6-naphthyridin-6(5H)-yl]carbonyl]-, cis- | [Molecular Formula]
C28H32FN3O5 | [MDL Number]
MFCD31813652 | [MOL File]
1854901-94-2.mol | [Molecular Weight]
509.57 |
| Hazard Information | Back Directory | [Description]
TAK-828F is a potent and selective orally available RORγt inverse agonist. TAK-828F showed Binding IC50 = 1.9 nM; Reporter gene IC50=6.1 nM; logD=3.53; LLE (reporter gene)=4.68. TAK-828F inhibited IL-17 production from mouse splenocytes and human peripheral blood mononuclear cells dose-dependently at concentrations of 0.01-10?μM without affecting the production of IFN-γ. TAK-828F may provide a novel therapeutic option to treat immune diseases by inhibiting Th17 and Th1/17 cells' differentiation and improving imbalance between Th17 and Treg cells. | [Uses]
TAK-828F is a potent, selective, and orally available retinoic acid receptor-related orphan receptor γt (RORγt) inverse agonist (binding IC50=1.9 nM, reporter gene IC50=6.1 nM). TAK-828F shows excellent RORγt isoforms selectivity (>5000-fold selectivity against human RORα and RORβ)[1]. | [in vivo]
TAK-828F (0.3, 1, and 3 mg/kg; orally administered; b.i.d.; 28 days; in mice with IL-23-induced cytokine expression model) shows robust and dose-dependent inhibition of IL-17A expression with an ED80 of 0.5 mg/kg[1]. | Animal Model: | Mice with IL-23-induced cytokine expression model[1] | | Dosage: | 0.3, 1, and 3 mg/kg | | Administration: | Orally administered; b.i.d.; 28 days | | Result: | Showed robust and dose-dependent inhibition of IL-17A expression (ED80=0.5 mg/kg). |
| [References]
[1] Kono M, et al. Discovery of [ cis-3-({(5 R)-5-[(7-Fluoro-1,1-dimethyl-2,3-dihydro-1 H-inden-5-yl)carbamoyl]-2-methoxy-7,8-dihydro-1,6-naphthyridin-6(5 H)-yl}carbonyl)cyclobutyl]acetic Acid (TAK-828F) as a Potent, Selective, and Orally Available Novel Reti DOI:10.1021/acs.jmedchem.8b00061 |
|
| Company Name: |
Biorbyt Ltd.
|
| Tel: |
+44 (0)1223 859 353 |
| Website: |
http://www.biorbyt.com |
|