WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H205909
CAS#: 928134-65-0 (free base)
Description: Osilodrostat, also known as LCI699, is a potent inhibitor of 11β-hydroxylase, the enzyme which catalyzes the final step of cortisol synthesis. LCI699 may thus be a potential new treatment for all forms of Cushing's syndrome. Current evidence indicates that the novel aldosterone inhibitor LCI699 is an effective and well-tolerated antihypertensive agent that lowers plasma aldosterone concentration and produces a mild ACTH-stimulated cortisol response suppressive effect.
Hodoodo Cat#: H205909
Name: Osilodrostat free base
CAS#: 928134-65-0 (free base)
Chemical Formula: C13H10FN3
Exact Mass: 227.09
Molecular Weight: 227.237
Elemental Analysis: C, 68.71; H, 4.44; F, 8.36; N, 18.49
Related CAS #: 928134-65-0 (free base) 928134-31-0 (free base) 1315449-72-9 (phosphate),
Synonym: LCI699; LCI 699; LCI-699; Osilodrostat; Osilodrostat free base
IUPAC/Chemical Name: (R)-4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorobenzonitrile
InChi Key: USUZGMWDZDXMDG-CYBMUJFWSA-N
InChi Code: InChI=1S/C13H10FN3/c14-12-5-9(6-15)1-3-11(12)13-4-2-10-7-16-8-17(10)13/h1,3,5,7-8,13H,2,4H2/t13-/m1/s1
SMILES Code: N#CC1=CC=C([C@H]2CCC3=CN=CN32)C(F)=C1
Appearance: Solid powder
Purity: >98%
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >5 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info:
| Biological target: | Osilodrostat (LCI699) is a potent inhibitor of human 11β-hydroxylase and aldosterone synthase with IC50 values of 2.5 and 0.7 nM, respectively. |
| In vitro activity: | HAC15 cells, 17 primary human adrenocortical cell cultures, and pituitary adenoma cells were incubated with osilodrostat, metyrapone, or ketoconazole (0.01 to 10 µM). In HAC15 cells, osilodrostat inhibited cortisol production more potently (IC50: 0.035 µM) than metyrapone (0.068 µM; P < 0.0001), and ketoconazole (0.621 µM; P < 0.0001). IC50 values of osilodrostat and metyrapone for basal cortisol production varied with a 25- and 18-fold difference, respectively, with comparable potency. Aldosterone production was inhibited more potently by osilodrostat vs metyrapone and ketoconazole. Osilodrostat and metyrapone treatment resulted in strong inhibition of corticosterone and cortisol, 11-deoxycortisol accumulation, and modest effects on adrenal androgens. No pituitary-directed effects of osilodrostat were observed. In conclusion, Osilodrostat might inhibit CYP11B1 and CYP11B2, in some conditions to a lesser extent CYP17A1 activity, and a proximal step in the steroidogenesis. Osilodrostat is a promising treatment option for Cushing syndrome. Reference: J Clin Endocrinol Metab. 2019 Aug 1;104(8):3437-3449. https://pubmed.ncbi.nlm.nih.gov/31127821/ |
| In vivo activity: | Sixty male and 60 female rats were randomized into single-sex groups to receive daily doses of pasireotide (0.3mg/kg/day, subcutaneously), osilodrostat (20mg/kg/day, orally), osilodrostat/pasireotide in combination (low dose, 1.5/0.03mg/kg/day; mid-dose, 5/0.1mg/kg/day; or high dose, 20/0.3mg/kg/day), or vehicle for 13weeks. Mean body-weight gains from baseline to Week 13 were significantly lower in the pasireotide-alone and combined-treatment groups compared to controls, and were significantly higher in female rats receiving osilodrostat monotherapy. Osilodrostat monotherapy was associated with significant changes in the histology and mean weights of the pituitary and adrenal glands, liver, and ovary/oviduct. Osilodrostat alone was associated with adrenocortical hypertrophy and hepatocellular hypertrophy. Cmax and AUC0-24h of osilodrostat and pasireotide increased in an approximately dose-proportional manner. Reference: Toxicol Appl Pharmacol. 2015 Aug 1;286(3):224-33. https://pubmed.ncbi.nlm.nih.gov/25981165/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 147.5 | 649.10 | |
| Ethanol | 72.5 | 319.05 |
The following data is based on the product molecular weight 227.24 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Creemers SG, Feelders RA, de Jong FH, Franssen GJH, de Rijke YB, van Koetsveld PM, Hofland LJ. 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. PMID: 31127821. 2. Li L, Vashisht K, Boisclair J, Li W, Lin TH, Schmid HA, Kluwe W, Schoenfeld H, Hoffmann P. 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. Epub 2015 May 14. PMID: 25981165. |
| In vitro protocol: | 1. Creemers SG, Feelders RA, de Jong FH, Franssen GJH, de Rijke YB, van Koetsveld PM, Hofland LJ. 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. PMID: 31127821. |
| In vivo protocol: | 1. Li L, Vashisht K, Boisclair J, Li W, Lin TH, Schmid HA, Kluwe W, Schoenfeld H, Hoffmann P. 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. Epub 2015 May 14. PMID: 25981165. |
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