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BI 135585

Names

[ CAS No. ]:
1114561-85-1

[ Name ]:
BI 135585

[Synonym ]:
(6S)-6-(2-Hydroxy-2-methylpropyl)-3-{(1S)-1-[4-(1-methyl-2-oxo-1,2-dihydro-4-pyridinyl)phenyl]ethyl}-6-phenyl-1,3-oxazinan-2-one
BI-135585
DA4HT8614K
2H-1,3-Oxazin-2-one, 3-[(1S)-1-[4-(1,2-dihydro-1-methyl-2-oxo-4-pyridinyl)phenyl]ethyl]tetrahydro-6-(2-hydroxy-2-methylpropyl)-6-phenyl-, (6S)-

Biological Activity

[Description]:

BI-135585 is a potent, selective and orally active 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) inhibitor with an IC50 of 13 nM. BI-135585 exhibits >1000-fold selectivity over other hydroxysteroid dehydrogenases. BI-135585 can be used for type 2 diabetes research[1][2].

[Related Catalog]:

Signaling Pathways >> Others >> Others
Research Areas >> Metabolic Disease

[Target]

IC50: 13 nM (11β-HSD1)[1]


[In Vitro]

BI-135585 binds in the substrate binding pocket of the active site of 11β-HSD1. Cellular activity of BI-135585 is examined by determining inhibition of 11β-HSD1 activity in human preadipocytes, the average IC50 is 1 nM[1]. In human adipose tissue ex vivo, BI-135585 inhibits the conversion of cortisone to cortisol with an average IC50 of 11 nM[1]. Abdominal subcutaneous and perirenal adipose tissue was harvested from one, male cynomolgus monkey. BI-135585 (20 hours) reduces enzyme activity in a dose-dependent manner with an IC50 of ~10 nM in perirenal adipose tissue and an IC50 of ~100 nM in abdominal subcutaneous adipose tissue[1].

[In Vivo]

BI-135585 (compound 11j; 1-3 mg/kg; po) inhibits 67% and 90% of enzyme activity respectively in perirenal adipose tissue in cynomolgus monkey[2].

[References]

[1]. Bradford S Hamilton, et al. Pharmacological characterization of the selective 11β-hydroxysteroid dehydrogenase 1 inhibitor, BI 135585, a clinical candidate for the treatment of type 2 diabetes. Eur J Pharmacol. 2015 Jan 5;746:50-5.

[2]. Linghang Zhuang, et al. Discovery of BI 135585, an in vivo efficacious oxazinanone-based 11β hydroxysteroid dehydrogenase type 1 inhibitor. Bioorg Med Chem. 2017 Jul 15;25(14):3649-3657.

Chemical & Physical Properties

[ Density]:
1.2±0.1 g/cm3

[ Boiling Point ]:
703.6±60.0 °C at 760 mmHg

[ Molecular Formula ]:
C28H32N2O4

[ Molecular Weight ]:
460.565

[ Flash Point ]:
379.3±32.9 °C

[ Exact Mass ]:
460.236206

[ LogP ]:
3.69

[ Vapour Pressure ]:
0.0±2.3 mmHg at 25°C

[ Index of Refraction ]:
1.596

Related Compounds