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Osilodrostat

Names

[ CAS No. ]:
928134-65-0

[ Name ]:
Osilodrostat

[Synonym ]:
osilodrostat
4-(quinolin-3-ylmethyl-amino)-benzenesulfonamide
Novartis LCI699
(R)-4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorobenzonitrile
UNII-5YL4IQ1078
4-[(5R)-6,7-Dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl]-3-fluorobenzonitrile
Benzonitrile, 4-[(5R)-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl]-3-fluoro-
3-<N-(4'-Amidosulfonylphenyl)aminomethyl>quinoline
4-((R)-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluoro-benzonitrile

Biological Activity

[Description]:

Osilodrostat (LCI699) is a potent inhibitor of human 11β-hydroxylase and aldosterone synthase with IC50 values of 2.5 and 0.7 nM, respectively.

[Related Catalog]:

Signaling Pathways >> Metabolic Enzyme/Protease >> Mineralocorticoid Receptor
Research Areas >> Cancer
Research Areas >> Inflammation/Immunology

[Target]

IC50: 2.5 nM (human 11β-hydroxylase), 0.7 nM (aldosterone synthase)[1]


[In Vivo]

Osilodrostat and pasireotide monotherapies are associated with significant changes in the histology and mean weights of the pituitary and adrenal glands, liver, and ovary/oviduct. Osilodrostat alone is associated with adrenocortical hypertrophy and hepatocellular hypertrophy. In combination, osilodrostat/pasireotide does not exacerbate any target organ changes and ameliorated the liver and adrenal gland changes observed with monotherapy. Cmax and AUC0–24h of osilodrostat and pasireotide increase in an approximately dose-proportional manner[1]. Osilodrostat treatment reduces urinary free cortisol in patients with Cushing's disease; 78.9% has normal urinary free cortisol at week 22. Treatment with osilodrostat is generally well tolerated[2].

[Animal admin]

Rats: Sixty male and 60 female rats are randomized into single-sex groups to receive daily doses of pasireotide (0.3 mg/kg/day, subcutaneously), osilodrostat (20 mg/kg/day, orally), osilodrostat/pasireotide in combination (low dose, 1.5/0.03 mg/kg/day; mid-dose, 5/0.1 mg/kg/day; or high dose, 20/0.3 mg/kg/day), or vehicle for 13 weeks[1].

[References]

[1]. Li L, et al. Osilodrostat (LCI699), a potent 11β-hydroxylase inhibitor, administered in combination with the multireceptor-targeted somatostatin analog pasireotide: A 13-week study in rats. Toxicol Appl Pharmacol. 2015 Aug 1;286(3):224-33.

[2]. Fleseriu M, et al. Osilodrostat, a potent oral 11β-hydroxylase inhibitor: 22-week, prospective, Phase II study in Cushing's disease. Pituitary. 2016 Apr;19(2):138-48.


[Related Small Molecules]

Eplerenone | Esaxerenone | Fludrocortisone acetate | Deoxycorticosterone acetate | Canrenone | Apararenone | SC26304

Chemical & Physical Properties

[ Density]:
1.3±0.1 g/cm3

[ Boiling Point ]:
433.8±45.0 °C at 760 mmHg

[ Molecular Formula ]:
C13H10FN3

[ Molecular Weight ]:
227.237

[ Flash Point ]:
216.2±28.7 °C

[ Exact Mass ]:
227.085876

[ PSA ]:
41.61000

[ LogP ]:
1.13

[ Vapour Pressure ]:
0.0±1.0 mmHg at 25°C

[ Index of Refraction ]:
1.664

[ Storage condition ]:
-20℃

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Related Compounds