| Identification | Back Directory | [Name]
Osilodrostat(LCI699) phosphate | [CAS]
1315449-72-9 | [Synonyms]
LCI 699;LCI-699
LCI699 phosphate
LCI-699 phosphate
LCI 699 phosphate
Osilodrostat phosphate
Osilodrostat(LCI699) phosphate | [Molecular Formula]
C13H13FN3O4P | [MOL File]
1315449-72-9.mol | [Molecular Weight]
325.24 |
| Questions And Answer | Back Directory | [FDA Approval]
Osilodrostat received orphan drug designation from the USFDA and was approved in 2020 for the treatment of Cushing's disease.
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| Hazard Information | Back Directory | [Uses]
Osilodrostat (LCI699) phosphate is a potent, orally active11β-hydroxylase (CYP11B1) inhibitor with an IC50 value of 35 nM. Osilodrostat phosphate is a potent, orally aldosterone synthase (CYP11B2) inhibitor with IC50 values of 0.7 nM and 160 nM for human aldosterone synthase and rat aldosterone synthase, respectively. Osilodrostat phosphate inhibits aldosterone and corticosterone synthesis. Osilodrostat phosphate has blood pressure lowering ability. Osilodrostat phosphate can be used for research of Cushing syndrome (CS)[1][2][3]. | [in vivo]
Osilodrostat (LCI699; 0.1-100 mg/kg; p.o.; once) phosphate inhibits aldosterone and corticosterone synthesis in Ang-II- and ACTH-stimulated Sprague Dawley rats[1].
Osilodrostat (LCI699; 3-100 mg/kg; p.o.; daily, for 52 weeks) phosphate reduces mean arterial pressure and prolongs survival in dTG rats[1]. | Animal Model: | Male Ang-II- and ACTH-stimulated Sprague Dawley rats[1] | | Dosage: | 0.1, 0.3, 1 and 3 mg/kg (Ang-II-stimulated rats) and 1, 3, 10, 30 and 100 mg/kg (ACTH-stimulated rats) | | Administration: | Oral administration; once | | Result: | Inhibited the increase in plasma aldosterone concentrations stimulated by Ang II or ACTH in a dose-dependent manner. |
| Animal Model: | dTG rats[1] | | Dosage: | 3, 10, 30 and 100 mg/kg | | Administration: | Oral administration; daily, for 52 weeks | | Result: | Increased fractional LV (systolic and diastolic) shortening, normalized LV isovolumic relaxation time to RR (IVRT/RR) ratio and myocardial cell size and reduced LV weight in a dose-dependent manner. |
| [References]
[1] Ménard J, et, al. Aldosterone synthase inhibition: cardiorenal protection in animal disease models and translation of hormonal effects to human subjects. J Transl Med. 2014 Dec 10;12:340. DOI:10.1186/s12967-014-0340-9
[2] Creemers SG, et, al. Osilodrostat Is a Potential Novel Steroidogenesis Inhibitor for the Treatment of Cushing Syndrome: An In Vitro Study. J Clin Endocrinol Metab. 2019 Aug 1;104(8):3437-3449. DOI:10.1210/jc.2019-00217
[3] 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. DOI:10.1016/j.taap.2015.05.004 |
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