Osilodrostat (LCI699)

    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 205909

CAS#: 928134-65-0 (or 928134-31-0)

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.


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10mg
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100mg
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1g
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25mg
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200mg
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2g
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50mg
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500mg
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5g
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Osilodrostat (LCI699) is not in stock, but may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 205909
Name: Osilodrostat (LCI699)
CAS#: 928134-65-0 (or 928134-31-0)
Chemical Formula: C13H10FN3
Exact Mass: 227.08588
Molecular Weight: 227.237
Elemental Analysis: C, 68.71; H, 4.44; F, 8.36; N, 18.49


Synonym: LCI699; LCI 699; LCI-699; Osilodrostat

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


Technical Data

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).

Harmonized System Code:
293490


Additional Information

  
 
 
 


References

1: Guelho D, Grossman AB. Emerging drugs for Cushing's disease. Expert Opin Emerg Drugs. 2015 Sep;20(3):463-78. doi: 10.1517/14728214.2015.1047762. Epub 2015 Jun 2. PubMed PMID: 26021183.

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. PubMed PMID: 25981165.

3: Papillon JP, Adams CM, Hu QY, Lou C, Singh AK, Zhang C, Carvalho J, Rajan S, Amaral A, Beil ME, Fu F, Gangl E, Hu CW, Jeng AY, LaSala D, Liang G, Logman M, Maniara WM, Rigel DF, Smith SA, Ksander GM. Structure-Activity Relationships, Pharmacokinetics, and in Vivo Activity of CYP11B2 and CYP11B1 Inhibitors. J Med Chem. 2015 Jun 11;58(11):4749-70. doi: 10.1021/acs.jmedchem.5b00407. Epub 2015 May 21. PubMed PMID: 25953419.

4: Fleseriu M. Medical treatment of Cushing disease: new targets, new hope. Endocrinol Metab Clin North Am. 2015 Mar;44(1):51-70. doi: 10.1016/j.ecl.2014.10.006. Epub 2014 Nov 4. Review. PubMed PMID: 25732642.

5: Wang HZ, Tian JB, Yang KH. Efficacy and safety of LCI699 for hypertension: a meta-analysis of randomized controlled trials and systematic review. Eur Rev Med Pharmacol Sci. 2015;19(2):296-304. Review. PubMed PMID: 25683946.

6: Daniel E, Newell-Price JD. Therapy of endocrine disease: steroidogenesis enzyme inhibitors in Cushing's syndrome. Eur J Endocrinol. 2015 Jun;172(6):R263-80. doi: 10.1530/EJE-14-1014. Epub 2015 Jan 30. Review. PubMed PMID: 25637072.

7: Fleseriu M, Petersenn S. Medical therapy for Cushing's disease: adrenal steroidogenesis inhibitors and glucocorticoid receptor blockers. Pituitary. 2015 Apr;18(2):245-52. doi: 10.1007/s11102-014-0627-0. PubMed PMID: 25560275.

8: Ménard J, Rigel DF, Watson C, Jeng AY, Fu F, Beil M, Liu J, Chen W, Hu CW, Leung-Chu J, LaSala D, Liang G, Rebello S, Zhang Y, Dole WP. 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. PubMed PMID: 25491597; PubMed Central PMCID: PMC4301837.

9: Oki Y. Medical management of functioning pituitary adenoma: an update. Neurol Med Chir (Tokyo). 2014;54(12):958-65. Epub 2014 Nov 29. PubMed PMID: 25446388.

10: Cai TQ, Stribling S, Tong X, Xu L, Wisniewski T, Fontenot JA, Struthers M, Akinsanya KO. Rhesus monkey model for concurrent analyses of in vivo selectivity, pharmacokinetics and pharmacodynamics of aldosterone synthase inhibitors. J Pharmacol Toxicol Methods. 2015 Jan-Feb;71:137-46. doi: 10.1016/j.vascn.2014.09.011. Epub 2014 Oct 7. PubMed PMID: 25304940.

11: Lother A, Moser M, Bode C, Feldman RD, Hein L. Mineralocorticoids in the heart and vasculature: new insights for old hormones. Annu Rev Pharmacol Toxicol. 2015;55:289-312. doi: 10.1146/annurev-pharmtox-010814-124302. Epub 2014 Sep 10. Review. PubMed PMID: 25251996.

12: Cuevas-Ramos D, Fleseriu M. Treatment of Cushing's disease: a mechanistic update. J Endocrinol. 2014 Nov;223(2):R19-39. doi: 10.1530/JOE-14-0300. Epub 2014 Aug 18. Review. PubMed PMID: 25134660.

13: Yin L, Hu Q, Emmerich J, Lo MM, Metzger E, Ali A, Hartmann RW. Novel pyridyl- or isoquinolinyl-substituted indolines and indoles as potent and selective aldosterone synthase inhibitors. J Med Chem. 2014 Jun 26;57(12):5179-89. doi: 10.1021/jm500140c. Epub 2014 Jun 5. PubMed PMID: 24899257.

14: Li W, Luo S, Rebello S, Flarakos J, Tse FL. A semi-automated LC-MS/MS method for the determination of LCI699, a steroid 11β-hydroxylase inhibitor, in human plasma. J Chromatogr B Analyt Technol Biomed Life Sci. 2014 Jun 1;960:182-93. doi: 10.1016/j.jchromb.2014.04.012. Epub 2014 Apr 30. PubMed PMID: 24814004.

15: Trainer PJ. Next generation medical therapy for Cushing's syndrome--can we measure a benefit? J Clin Endocrinol Metab. 2014 Apr;99(4):1157-60. doi: 10.1210/jc.2014-1054. PubMed PMID: 24702012.

16: Bertagna X, Pivonello R, Fleseriu M, Zhang Y, Robinson P, Taylor A, Watson CE, Maldonado M, Hamrahian AH, Boscaro M, Biller BM. LCI699, a potent 11β-hydroxylase inhibitor, normalizes urinary cortisol in patients with Cushing's disease: results from a multicenter, proof-of-concept study. J Clin Endocrinol Metab. 2014 Apr;99(4):1375-83. doi: 10.1210/jc.2013-2117. Epub 2013 Dec 11. PubMed PMID: 24423285.

17: Oki Y. Medical management of functioning pituitary adenoma: an update. Neurol Med Chir (Tokyo). 2014;54 Suppl 3:958-65. PubMed PMID: 26236804.

18: Schumacher CD, Steele RE, Brunner HR. Aldosterone synthase inhibition for the treatment of hypertension and the derived mechanistic requirements for a new therapeutic strategy. J Hypertens. 2013 Oct;31(10):2085-93. doi: 10.1097/HJH.0b013e328363570c. PubMed PMID: 24107737; PubMed Central PMCID: PMC3771574.

19: Brown NJ. Contribution of aldosterone to cardiovascular and renal inflammation and fibrosis. Nat Rev Nephrol. 2013 Aug;9(8):459-69. doi: 10.1038/nrneph.2013.110. Epub 2013 Jun 18. Review. PubMed PMID: 23774812; PubMed Central PMCID: PMC3922409.

20: van der Pas R, de Herder WW, Hofland LJ, Feelders RA. Recent developments in drug therapy for Cushing's disease. Drugs. 2013 Jun;73(9):907-18. doi: 10.1007/s40265-013-0067-6. Review. PubMed PMID: 23737437.