[CAS NO. 928134-65-0] Osilodrostat
PRODUCTS SPECIFICATIONS [928134-65-0]
DESCRIPTION [928134-65-0]
Overview
| MDL | MFCD25976825 |
|---|---|
| Molecular Weight | 227.24 |
| Molecular Formula | C13H10FN3 |
| SMILES | N#CC1=CC=C([C@H]2CCC3=CN=CN32)C(F)=C1 |
2 Publications Citing Use of MCE
Summary
Osilodrostat (LCI699) is a potent, orally active11β-hydroxylase (CYP11B1) inhibitor with an IC 50 value of 35 nM. Osilodrostat is a potent, orally aldosterone synthase (CYP11B2) inhibitor with IC 50 values of 0.7 nM and 160 nM for human aldosterone synthase and rat aldosterone synthase, respectively. Osilodrostat inhibits aldosterone and corticosterone synthesis. Osilodrostat has blood pressure lowering ability. Osilodrostat can be used for research of Cushing syndrome (CS) [1] [2] [3] .
IC50 & Target
In Vitro
Osilodrostat (LCI699; 0.01-10 µM; HAC15 cells, 17 primary human adrenocortical cell cultures, and pituitary adenoma cells) inhibits cortisol and aldosterone. Osilodrostat results in inhibition of corticosterone, 11-deoxycortisol accumulation, and modest effects on adrenal androgens [2] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
Osilodrostat (LCI699; 0.1-100 mg/kg; p.o.; once) 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) reduces mean arterial pressure and prolongs survival in dTG rats
[1]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| 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. |
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT00817414 | Novartis|Great Lakes Drug Development, Inc.|Integrium |
Hypertension
|
January 14, 2009 | Phase 2 |
| NCT05382156 | RECORDATI GROUP |
Endogenous Cushing´s Syndrome
|
June 2022 | |
| NCT03606408 | RECORDATI GROUP |
Cushing´s Syndrome
|
October 5, 2018 | Phase 2 |
| NCT00732771 | Novartis |
Primary Hyperaldosteronism
|
June 2008 | Phase 2 |
| NCT00758524 | Novartis Pharmaceuticals|Novartis |
Essential Hypertension
|
September 11, 2008 | Phase 2 |
| NCT02372084 | Novartis Pharmaceuticals|Novartis |
Hepatic Impairment
|
April 21, 2015 | Phase 1 |
| NCT01331239 | Novartis Pharmaceuticals|Novartis |
Cushings Disease|Cushing Disease
|
March 23, 2011 | Phase 2 |
| NCT02468193 | Novartis Pharmaceuticals|Novartis |
Cushing´s Syndrome|Ectopic Corticotropin Syndrome|Adrenal Adenoma|Adrenal Carcinoma|AIMAH|PPNAD
|
September 24, 2015 | Phase 2 |
| NCT02399202 | Novartis Pharmaceuticals|Novartis |
Renal Impairment
|
November 6, 2015 | Phase 1 |
| NCT02180217 | Novartis Pharmaceuticals|Novartis |
Cushings Disease
|
October 6, 2014 | Phase 3 |
| NCT00817635 | Novartis|Great Lakes Drug Development, Inc.|Integrium |
Hypertension
|
December 22, 2008 | Phase 2 |
| NCT03708900 | RECORDATI GROUP |
Cushing´s Disease
|
April 28, 2021 | Phase 2 |
| NCT02697734 | Novartis Pharmaceuticals|Novartis |
Cushing´s Disease
|
October 3, 2016 | Phase 3 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 250 mg/mL ( 1100.16 mM ; Need ultrasonic)
Ethanol : 100 mg/mL ( 440.06 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 4.4006 mL | 22.0032 mL | 44.0063 mL |
| 5 mM | 0.8801 mL | 4.4006 mL | 8.8013 mL |
| 10 mM | 0.4401 mL | 2.2003 mL | 4.4006 mL |
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1.
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2.
Add each solvent one by one: 10% DMSO >> 90% (20% SBE-β-CD in saline)
Solubility: ≥ 2.5 mg/mL (11.00 mM); Clear solution
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3.
Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 2.5 mg/mL (11.00 mM); Clear solution
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4.
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5.
Add each solvent one by one: 10% EtOH >> 90% (20% SBE-β-CD in saline)
Solubility: ≥ 2.5 mg/mL (11.00 mM); Clear solution
-
6.
Add each solvent one by one: 10% EtOH >> 90% corn oil
Solubility: ≥ 2.5 mg/mL (11.00 mM); Clear solution
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.
- [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.
- [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.
Synonyms
