928134-65-0

928134-65-0 structure

Name: Osilodrostat
Chemical Name: 4-[(5R)-6,7-Dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl]-3-fluorobenzo nitrile
CAS Number: 928134-65-0
Molecular Formula: C₁₃H₁₀FN₃
Molecular Weight: 227.237
Catalog: Signaling Pathways Metabolic Enzyme/Protease Mineralocorticoid Receptor
Create Date: 2017-01-23 08:40:53
Modify Date: 2024-01-06 14:13:47
Osilodrostat (LCI699) is a potent inhibitor of human 11β-hydroxylase and aldosterone synthase with IC50 values of 2.5 and 0.7 nM, respectively.

Name	4-[(5R)-6,7-Dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl]-3-fluorobenzo nitrile
Synonyms	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

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.

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℃

105942-09-4

928134-65-0

928134-66-1

Literature: Meredith, Erik L.; Ksander, Gary; Monovich, Lauren G.; Papillon, Julien P. N.; Liu, Qian; Miranda, Karl; Morris, Patrick; Rao, Chang; Burgis, Robin; Capparelli, Michael; Hu, Qi-Ying; Singh, Alok; Rigel, Dean F.; Jeng, Arco Y.; Beil, Michael; Fu, Fumin; Hu, Chii-Whei; Lasala, Daniel ACS Medicinal Chemistry Letters, 2013 , vol. 4, # 12 p. 1203 - 1207