U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C13H10FN3
Molecular Weight 227.2375
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of OSILODROSTAT

SMILES

c1cc(c(cc1C#N)F)[C@@]2([H])CCc3cncn32

InChI

InChIKey=USUZGMWDZDXMDG-CYBMUJFWSA-N
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

HIDE SMILES / InChI

Molecular Formula C13H10FN3
Molecular Weight 227.2375
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment:: https://clinicaltrials.gov/ct2/show/NCT02697734 | https://clinicaltrials.gov/ct2/show/NCT02468193 | https://clinicaltrials.gov/ct2/show/NCT02372084 | https://www.ncbi.nlm.nih.gov/pubmed/25981165

Osilodrostat (INN, USAN) (developmental code name LCI-699) is an orally active, non-steroidal corticosteroid biosynthesis inhibitor which is under development by Novartis for the treatment of Cushing's syndrome and pituitary ACTH hypersecretion (a specific subtype of Cushing's syndrome). Osilodrostat specifically acts as a potent and selective inhibitor of aldosterone synthase (CYP11B2) and at higher dosages of 11β-hydroxylase (CYP11B1). Osilodrostat decreases plasma and urinary aldosterone levels and rapidly corrects hypokalemia, in patients with primary aldosteronism and hypertension. At doses ≥1 mg o.d. Osilodrostat markedly increases 11-deoxycortisol plasma levels and blunts ACTH-stimulated cortisol release in ≈20% of patients, consistent with the inhibition of CYP11B1. In patients with resistant hypertension, Osilodrostat produces a non-significant reduction in blood pressure, possibly due to the increase in 11-deoxycortisol levels and the stimulation of the hypothalamic-pituitary-adrenal feedback axis. Because of the lack of selectivity, poor antihypertensive effect, and short half-life, the development of Osilodrostat as antihypertensive was halted. As of 2017, Osilodrostat is in phase III and phase II clinical trials for the treatment of pituitary ACTH hypersecretion and Cushing's syndrome, respectively.

Originator

Curator's Comment:: # Novartis A.-G.

Approval Year

Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
2340 ng/mL
5 mg/kg 1 times / day multiple, oral
dose: 5 mg/kg
route of administration: Oral
experiment type: MULTIPLE
co-administered: PASIREOTIDE
OSILODROSTAT plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
2100 ng/mL
5 mg/kg single, oral
dose: 5 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered: PASIREOTIDE
OSILODROSTAT plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
2170 ng/mL
5 mg/kg single, oral
dose: 5 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered: PASIREOTIDE
OSILODROSTAT plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: FEMALE
food status: FED
634 ng/mL
1.5 mg/kg single, oral
dose: 1.5 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered: PASIREOTIDE
OSILODROSTAT plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
999 ng/mL
1.5 mg/kg 1 times / day multiple, oral
dose: 1.5 mg/kg
route of administration: Oral
experiment type: MULTIPLE
co-administered: PASIREOTIDE
OSILODROSTAT plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
608 ng/mL
1.5 mg/kg single, oral
dose: 1.5 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered: PASIREOTIDE
OSILODROSTAT plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: FEMALE
food status: FED
6100 ng/mL
20 mg/kg 1 times / day multiple, oral
dose: 20 mg/kg
route of administration: Oral
experiment type: MULTIPLE
co-administered: PASIREOTIDE
OSILODROSTAT plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
7200 ng/mL
20 mg/kg single, oral
dose: 20 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered: PASIREOTIDE
OSILODROSTAT plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
2130 ng/mL
5 mg/kg 1 times / day multiple, oral
dose: 5 mg/kg
route of administration: Oral
experiment type: MULTIPLE
co-administered: PASIREOTIDE
OSILODROSTAT plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: FEMALE
food status: FED
5490 ng/mL
20 mg/kg single, oral
dose: 20 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
OSILODROSTAT plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: FEMALE
food status: FED
4930 ng/mL
20 mg/kg 1 times / day multiple, oral
dose: 20 mg/kg
route of administration: Oral
experiment type: MULTIPLE
co-administered: PASIREOTIDE
OSILODROSTAT plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: FEMALE
food status: FED
306 ng/mL
30 mg 2 times / day multiple, oral
dose: 30 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
OSILODROSTAT unknown
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
7.91 ng/mL
2 mg single, oral
dose: 2 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
OSILODROSTAT unknown
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
617 ng/mL
1.5 mg/kg 1 times / day multiple, oral
dose: 1.5 mg/kg
route of administration: Oral
experiment type: MULTIPLE
co-administered: PASIREOTIDE
OSILODROSTAT plasma
Rattus norvegicus
population: HEALTHY
age: UNKNOWN
sex: FEMALE
food status: FED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
11500 ng × h/mL
5 mg/kg 1 times / day multiple, oral
dose: 5 mg/kg
route of administration: Oral
experiment type: MULTIPLE
co-administered: PASIREOTIDE
OSILODROSTAT plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
12700 ng × h/mL
5 mg/kg single, oral
dose: 5 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered: PASIREOTIDE
OSILODROSTAT plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
15700 ng × h/mL
5 mg/kg single, oral
dose: 5 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered: PASIREOTIDE
OSILODROSTAT plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: FEMALE
food status: FED
2450 ng × h/mL
1.5 mg/kg single, oral
dose: 1.5 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered: PASIREOTIDE
OSILODROSTAT plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
2690 ng × h/mL
1.5 mg/kg 1 times / day multiple, oral
dose: 1.5 mg/kg
route of administration: Oral
experiment type: MULTIPLE
co-administered: PASIREOTIDE
OSILODROSTAT plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
2730 ng × h/mL
1.5 mg/kg single, oral
dose: 1.5 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered: PASIREOTIDE
OSILODROSTAT plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: FEMALE
food status: FED
50000 ng × h/mL
20 mg/kg 1 times / day multiple, oral
dose: 20 mg/kg
route of administration: Oral
experiment type: MULTIPLE
co-administered: PASIREOTIDE
OSILODROSTAT plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
98000 ng × h/mL
20 mg/kg single, oral
dose: 20 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered: PASIREOTIDE
OSILODROSTAT plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
13300 ng × h/mL
5 mg/kg 1 times / day multiple, oral
dose: 5 mg/kg
route of administration: Oral
experiment type: MULTIPLE
co-administered: PASIREOTIDE
OSILODROSTAT plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: FEMALE
food status: FED
80400 ng × h/mL
20 mg/kg single, oral
dose: 20 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
OSILODROSTAT plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: FEMALE
food status: FED
51600 ng × h/mL
20 mg/kg 1 times / day multiple, oral
dose: 20 mg/kg
route of administration: Oral
experiment type: MULTIPLE
co-administered: PASIREOTIDE
OSILODROSTAT plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: FEMALE
food status: FED
1680 ng × h/mL
30 mg 2 times / day multiple, oral
dose: 30 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
OSILODROSTAT unknown
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
38.6 ng × h/mL
2 mg single, oral
dose: 2 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
OSILODROSTAT unknown
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
3010 ng × h/mL
1.5 mg/kg 1 times / day multiple, oral
dose: 1.5 mg/kg
route of administration: Oral
experiment type: MULTIPLE
co-administered: PASIREOTIDE
OSILODROSTAT plasma
Rattus norvegicus
population: HEALTHY
age: UNKNOWN
sex: FEMALE
food status: FED
Doses

Doses

DosePopulationAdverse events​
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Disc. AE: Hypocortisolism...
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Disc. AE: Hypokalemia, Pituitary tumor NOS...
Other AEs: Adrenal insufficiency, Fatigue...
AEs leading to
discontinuation/dose reduction:
Hypokalemia (0.72%)
Pituitary tumor NOS (5.8%)
Other AEs:
Adrenal insufficiency (43.1%)
Fatigue (38.7%)
Nausea (grade 1-2, 37.2%)
Headache (30.7%)
Edema (21.2%)
Nasopharyngitis (19.7%)
Vomiting (grade 1-2, 19%)
Arthralgia (17.5%)
Back pain (15.3%)
Rash (15.3%)
Diarrhea (grade 1-2, 14.6%)
Blood corticotrophin increased (13.9%)
Dizziness (13.9%)
Abdominal pain (grade 1-2, 13.1%)
Hypokalaemia (12.4%)
Myalgia (12.4%)
Decreased appetite (11.7%)
Hormone level abnormal (11.7%)
Hypotension (11.7%)
Urinary tract infection (11.7%)
Blood testosterone increased (10.9%)
Pyrexia (10.9%)
Anemia (10.2%)
Cough (10.2%)
Hypertension (10.2%)
Influenza (10.2%)
Adrenal insufficiency (43.1%)
Fatigue (38.7%)
Nausea (grade 1-2, 37.2%)
Headache (30.7%)
Edema (21.2%)
Nasopharyngitis (19.7%)
Vomiting (grade 1-2, 19%)
Arthralgia (17.5%)
Back pain (15.3%)
Rash (15.3%)
Diarrhea (grade 1-2, 14.6%)
Blood corticotrophin increased (13.9%)
Dizziness (13.9%)
Abdominal pain (grade 1-2, 13.1%)
Hypokalaemia (12.4%)
Myalgia (12.4%)
Decreased appetite (11.7%)
Hormone level abnormal (11.7%)
Hypotension (11.7%)
Urinary tract infection (11.7%)
Blood testosterone increased (10.9%)
Pyrexia (10.9%)
Anemia (10.2%)
Cough (10.2%)
Hypertension (10.2%)
Influenza (10.2%)
Hirsutism (9.5%)
Acne (8.8%)
Dyspepsia (8%)
Insomnia (8%)
Anxiety (7.3%)
Depression (7.3%)
Gastroenteritis (7.3%)
Malaise (6.6%)
Tachycardia (6.6%)
Alopecia (5.8%)
Transaminases increased (4.4%)
QT interval prolonged (3.6%)
Syncope (1.5%)
Neutropenia (1.4%)
Neutrophil count decreased (13.1%)
ALT increased (grade 1, 4%)
AST increased (grade 1, 4%)
Sources:
5 mg 2 times / day steady, oral
Recommended
Dose: 5 mg, 2 times / day
Route: oral
Route: steady
Dose: 5 mg, 2 times / day
Sources:
unhealthy, 20-69 years
Health Status: unhealthy
Age Group: 20-69 years
Sex: M+F
Sources:
DLT: Rash, Visual impairment...
Other AEs: Nausea, Anaemia...
Dose limiting toxicities:
Rash (3%)
Visual impairment (3%)
Headache (3%)
Paresis cranial nerve (3%)
Pituitary tumour benign (3%)
Hypocortisolism (3%)
Other AEs:
Nausea (11%)
Anaemia (8%)
Arthralgia (8%)
Headache (8%)
Asthenia (6%)
Blood corticotrophin increased (6%)
Constipation (6%)
Depression (6%)
Dizziness (6%)
Fatigue (6%)
Hirsutism (6%)
Nasopharyngitis (6%)
Cough (3%)
Insomnia (3%)
Urinary tract infection (3%)
Sources:
200 mg 1 times / day single, oral
Highest studied dose
Dose: 200 mg, 1 times / day
Route: oral
Route: single
Dose: 200 mg, 1 times / day
Sources:
healthy
Other AEs: Electrocardiogram QTc interval prolonged...
30 mg 2 times / day steady, oral
Highest studied dose
unhealthy
30 mg 2 times / day steady, oral
Recommended
Dose: 30 mg, 2 times / day
Route: oral
Route: steady
Dose: 30 mg, 2 times / day
Sources:
unhealthy
150 mg single, oral
Studied dose
healthy
Other AEs: QT interval prolonged...
20 mg 1 times / day steady, oral
Studied dose
Dose: 20 mg, 1 times / day
Route: oral
Route: steady
Dose: 20 mg, 1 times / day
Sources:
unhealthy
Other AEs: Headache, Adrenal insufficiency...
Other AEs:
Headache (grade 3-5, 5.3%)
Adrenal insufficiency (grade 3-5, 5.3%)
Hypertension (grade 3-5, 21.1%)
Anaemia (grade 3-5, 5.3%)
Depression (grade 3-5, 5.3%)
Lipase increased (grade 3-5, 5.3%)
Pituitary-dependent Cushing's syndrome (grade 3-5, 15.8%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Hypocortisolism Disc. AE
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Hypokalemia 0.72%
Disc. AE
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Neutropenia 1.4%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Syncope 1.5%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Anemia 10.2%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Anemia 10.2%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Cough 10.2%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Cough 10.2%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Hypertension 10.2%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Hypertension 10.2%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Influenza 10.2%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Influenza 10.2%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Blood testosterone increased 10.9%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Blood testosterone increased 10.9%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Pyrexia 10.9%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Pyrexia 10.9%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Decreased appetite 11.7%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Decreased appetite 11.7%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Hormone level abnormal 11.7%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Hormone level abnormal 11.7%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Hypotension 11.7%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Hypotension 11.7%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Urinary tract infection 11.7%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Urinary tract infection 11.7%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Hypokalaemia 12.4%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Hypokalaemia 12.4%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Myalgia 12.4%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Myalgia 12.4%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Neutrophil count decreased 13.1%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Blood corticotrophin increased 13.9%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Blood corticotrophin increased 13.9%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Dizziness 13.9%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Dizziness 13.9%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Back pain 15.3%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Back pain 15.3%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Rash 15.3%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Rash 15.3%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Arthralgia 17.5%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Arthralgia 17.5%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Nasopharyngitis 19.7%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Nasopharyngitis 19.7%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Edema 21.2%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Edema 21.2%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
QT interval prolonged 3.6%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Headache 30.7%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Headache 30.7%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Fatigue 38.7%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Fatigue 38.7%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Transaminases increased 4.4%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Adrenal insufficiency 43.1%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Adrenal insufficiency 43.1%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Alopecia 5.8%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Pituitary tumor NOS 5.8%
Disc. AE
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Malaise 6.6%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Tachycardia 6.6%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Anxiety 7.3%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Depression 7.3%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Gastroenteritis 7.3%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Dyspepsia 8%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Insomnia 8%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Acne 8.8%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Hirsutism 9.5%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
ALT increased grade 1, 4%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
AST increased grade 1, 4%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Abdominal pain grade 1-2, 13.1%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Abdominal pain grade 1-2, 13.1%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Diarrhea grade 1-2, 14.6%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Diarrhea grade 1-2, 14.6%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Vomiting grade 1-2, 19%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Vomiting grade 1-2, 19%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Nausea grade 1-2, 37.2%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Nausea grade 1-2, 37.2%
7 mg 2 times / day steady, oral
Recommended
unhealthy, 19-70 years
Nausea 11%
5 mg 2 times / day steady, oral
Recommended
Dose: 5 mg, 2 times / day
Route: oral
Route: steady
Dose: 5 mg, 2 times / day
Sources:
unhealthy, 20-69 years
Health Status: unhealthy
Age Group: 20-69 years
Sex: M+F
Sources:
Cough 3%
5 mg 2 times / day steady, oral
Recommended
Dose: 5 mg, 2 times / day
Route: oral
Route: steady
Dose: 5 mg, 2 times / day
Sources:
unhealthy, 20-69 years
Health Status: unhealthy
Age Group: 20-69 years
Sex: M+F
Sources:
Insomnia 3%
5 mg 2 times / day steady, oral
Recommended
Dose: 5 mg, 2 times / day
Route: oral
Route: steady
Dose: 5 mg, 2 times / day
Sources:
unhealthy, 20-69 years
Health Status: unhealthy
Age Group: 20-69 years
Sex: M+F
Sources:
Urinary tract infection 3%
5 mg 2 times / day steady, oral
Recommended
Dose: 5 mg, 2 times / day
Route: oral
Route: steady
Dose: 5 mg, 2 times / day
Sources:
unhealthy, 20-69 years
Health Status: unhealthy
Age Group: 20-69 years
Sex: M+F
Sources:
Headache 3%
DLT
5 mg 2 times / day steady, oral
Recommended
Dose: 5 mg, 2 times / day
Route: oral
Route: steady
Dose: 5 mg, 2 times / day
Sources:
unhealthy, 20-69 years
Health Status: unhealthy
Age Group: 20-69 years
Sex: M+F
Sources:
Hypocortisolism 3%
DLT
5 mg 2 times / day steady, oral
Recommended
Dose: 5 mg, 2 times / day
Route: oral
Route: steady
Dose: 5 mg, 2 times / day
Sources:
unhealthy, 20-69 years
Health Status: unhealthy
Age Group: 20-69 years
Sex: M+F
Sources:
Paresis cranial nerve 3%
DLT
5 mg 2 times / day steady, oral
Recommended
Dose: 5 mg, 2 times / day
Route: oral
Route: steady
Dose: 5 mg, 2 times / day
Sources:
unhealthy, 20-69 years
Health Status: unhealthy
Age Group: 20-69 years
Sex: M+F
Sources:
Pituitary tumour benign 3%
DLT
5 mg 2 times / day steady, oral
Recommended
Dose: 5 mg, 2 times / day
Route: oral
Route: steady
Dose: 5 mg, 2 times / day
Sources:
unhealthy, 20-69 years
Health Status: unhealthy
Age Group: 20-69 years
Sex: M+F
Sources:
Rash 3%
DLT
5 mg 2 times / day steady, oral
Recommended
Dose: 5 mg, 2 times / day
Route: oral
Route: steady
Dose: 5 mg, 2 times / day
Sources:
unhealthy, 20-69 years
Health Status: unhealthy
Age Group: 20-69 years
Sex: M+F
Sources:
Visual impairment 3%
DLT
5 mg 2 times / day steady, oral
Recommended
Dose: 5 mg, 2 times / day
Route: oral
Route: steady
Dose: 5 mg, 2 times / day
Sources:
unhealthy, 20-69 years
Health Status: unhealthy
Age Group: 20-69 years
Sex: M+F
Sources:
Asthenia 6%
5 mg 2 times / day steady, oral
Recommended
Dose: 5 mg, 2 times / day
Route: oral
Route: steady
Dose: 5 mg, 2 times / day
Sources:
unhealthy, 20-69 years
Health Status: unhealthy
Age Group: 20-69 years
Sex: M+F
Sources:
Blood corticotrophin increased 6%
5 mg 2 times / day steady, oral
Recommended
Dose: 5 mg, 2 times / day
Route: oral
Route: steady
Dose: 5 mg, 2 times / day
Sources:
unhealthy, 20-69 years
Health Status: unhealthy
Age Group: 20-69 years
Sex: M+F
Sources:
Constipation 6%
5 mg 2 times / day steady, oral
Recommended
Dose: 5 mg, 2 times / day
Route: oral
Route: steady
Dose: 5 mg, 2 times / day
Sources:
unhealthy, 20-69 years
Health Status: unhealthy
Age Group: 20-69 years
Sex: M+F
Sources:
Depression 6%
5 mg 2 times / day steady, oral
Recommended
Dose: 5 mg, 2 times / day
Route: oral
Route: steady
Dose: 5 mg, 2 times / day
Sources:
unhealthy, 20-69 years
Health Status: unhealthy
Age Group: 20-69 years
Sex: M+F
Sources:
Dizziness 6%
5 mg 2 times / day steady, oral
Recommended
Dose: 5 mg, 2 times / day
Route: oral
Route: steady
Dose: 5 mg, 2 times / day
Sources:
unhealthy, 20-69 years
Health Status: unhealthy
Age Group: 20-69 years
Sex: M+F
Sources:
Fatigue 6%
5 mg 2 times / day steady, oral
Recommended
Dose: 5 mg, 2 times / day
Route: oral
Route: steady
Dose: 5 mg, 2 times / day
Sources:
unhealthy, 20-69 years
Health Status: unhealthy
Age Group: 20-69 years
Sex: M+F
Sources:
Hirsutism 6%
5 mg 2 times / day steady, oral
Recommended
Dose: 5 mg, 2 times / day
Route: oral
Route: steady
Dose: 5 mg, 2 times / day
Sources:
unhealthy, 20-69 years
Health Status: unhealthy
Age Group: 20-69 years
Sex: M+F
Sources:
Nasopharyngitis 6%
5 mg 2 times / day steady, oral
Recommended
Dose: 5 mg, 2 times / day
Route: oral
Route: steady
Dose: 5 mg, 2 times / day
Sources:
unhealthy, 20-69 years
Health Status: unhealthy
Age Group: 20-69 years
Sex: M+F
Sources:
Anaemia 8%
5 mg 2 times / day steady, oral
Recommended
Dose: 5 mg, 2 times / day
Route: oral
Route: steady
Dose: 5 mg, 2 times / day
Sources:
unhealthy, 20-69 years
Health Status: unhealthy
Age Group: 20-69 years
Sex: M+F
Sources:
Arthralgia 8%
5 mg 2 times / day steady, oral
Recommended
Dose: 5 mg, 2 times / day
Route: oral
Route: steady
Dose: 5 mg, 2 times / day
Sources:
unhealthy, 20-69 years
Health Status: unhealthy
Age Group: 20-69 years
Sex: M+F
Sources:
Headache 8%
5 mg 2 times / day steady, oral
Recommended
Dose: 5 mg, 2 times / day
Route: oral
Route: steady
Dose: 5 mg, 2 times / day
Sources:
unhealthy, 20-69 years
Health Status: unhealthy
Age Group: 20-69 years
Sex: M+F
Sources:
Electrocardiogram QTc interval prolonged
200 mg 1 times / day single, oral
Highest studied dose
Dose: 200 mg, 1 times / day
Route: oral
Route: single
Dose: 200 mg, 1 times / day
Sources:
healthy
QT interval prolonged 3.6%
150 mg single, oral
Studied dose
healthy
Pituitary-dependent Cushing's syndrome grade 3-5, 15.8%
20 mg 1 times / day steady, oral
Studied dose
Dose: 20 mg, 1 times / day
Route: oral
Route: steady
Dose: 20 mg, 1 times / day
Sources:
unhealthy
Hypertension grade 3-5, 21.1%
20 mg 1 times / day steady, oral
Studied dose
Dose: 20 mg, 1 times / day
Route: oral
Route: steady
Dose: 20 mg, 1 times / day
Sources:
unhealthy
Adrenal insufficiency grade 3-5, 5.3%
20 mg 1 times / day steady, oral
Studied dose
Dose: 20 mg, 1 times / day
Route: oral
Route: steady
Dose: 20 mg, 1 times / day
Sources:
unhealthy
Anaemia grade 3-5, 5.3%
20 mg 1 times / day steady, oral
Studied dose
Dose: 20 mg, 1 times / day
Route: oral
Route: steady
Dose: 20 mg, 1 times / day
Sources:
unhealthy
Depression grade 3-5, 5.3%
20 mg 1 times / day steady, oral
Studied dose
Dose: 20 mg, 1 times / day
Route: oral
Route: steady
Dose: 20 mg, 1 times / day
Sources:
unhealthy
Headache grade 3-5, 5.3%
20 mg 1 times / day steady, oral
Studied dose
Dose: 20 mg, 1 times / day
Route: oral
Route: steady
Dose: 20 mg, 1 times / day
Sources:
unhealthy
Lipase increased grade 3-5, 5.3%
20 mg 1 times / day steady, oral
Studied dose
Dose: 20 mg, 1 times / day
Route: oral
Route: steady
Dose: 20 mg, 1 times / day
Sources:
unhealthy
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
moderate [Ki 0.175 uM]
moderate [Ki 1 uM]
no [IC50 3.23 uM]
no [IC50 45 uM]
no [IC50 >100 uM]
no [IC50 >100 uM]
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
weak [Ki 2 uM]
weak [Ki 20 uM]
weak [Ki 3.25 uM]
yes [IC50 0.7 uM]
yes [IC50 0.7 uM]
yes [IC50 19.9 uM]
yes [IC50 30 uM]
yes [IC50 37.7 uM]
yes [IC50 5.57 uM]
yes [IC50 67.6 uM]
yes [IC50 8.59 uM]
yes [IC50 >50 uM]
yes [IC50 >50 uM]
yes [Ki 0.482 uM]
yes [Ki 10 uM]
yes [Ki 225 uM]
yes [Ki 86.3 uM]
yes
yes
yes
yes
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
no
yes [Km 30.4 uM]
unlikely
Comment: Due to the available high Km,u values (~30 μM) for CYP3A4, CYP2B6 and CYP2D6, these enzymes are not likely saturated at clinically relevant doses since Cmax is about 0.88 μM following multiple dose administration of 30 mg osilodrostat twice daily
Page: 9
yes [Km 36.1 uM]
unlikely
Comment: Due to the available high Km,u values (~30 μM) for CYP3A4, CYP2B6 and CYP2D6, these enzymes are not likely saturated at clinically relevant doses since Cmax is about 0.88 μM following multiple dose administration of 30 mg osilodrostat twice daily
Page: 9
yes [Km 36.1 uM]
unlikely
Comment: Due to the available high Km,u values (~30 μM) for CYP3A4, CYP2B6 and CYP2D6, these enzymes are not likely saturated at clinically relevant doses since Cmax is about 0.88 μM following multiple dose administration of 30 mg osilodrostat twice daily
Page: 9
yes
yes
yes
Tox targets

Tox targets

PubMed

PubMed

TitleDatePubMed
Efficacy and safety of LCI699 for hypertension: a meta-analysis of randomized controlled trials and systematic review.
2015
Medical treatment of Cushing disease: new targets, new hope.
2015 Mar
Patents

Sample Use Guides

1, 5, 10, or 20 mg/day for 48-weeks
Route of Administration: Oral
For in vitro measurement of aldosterone activity, human adrenocortical carcinoma NCI-H295R cells are seeded in NBS 96-well plates at a density of 25,000 cells/well in 100 μl of a growth medium containing DMEM/F12 supplemented with 10% FCS, 2.5% Nuserum, 1 μg ITS/ml, and 1x antibiotic/antimycotic. The medium is changed after culturing for 3 days at 37 C under an atmosphere of 5% CO2/95% air. On the following day, cells are rinsed with 100 μl of DMEM/F12 and incubated with 100 μl of treatment medium containing 1 µM Ang II and a compound 7n (Osilodrostat) at different concentrations in quadruplicate wells at 37C for 24 hr. At the end of incubation, 50 μl of medium is withdrawn from each well for measurement of aldosterone production by an RIA using mouse anti-aldosterone monoclonal antibodies.
Substance Class Chemical
Created
by admin
on Sat Jun 26 02:10:19 UTC 2021
Edited
by admin
on Sat Jun 26 02:10:19 UTC 2021
Record UNII
5YL4IQ1078
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
OSILODROSTAT
INN   USAN   WHO-DD  
USAN   INN  
Official Name English
LCI-699-NX
Code English
BENZONITRILE, 4-((5R)-6,7-DIHYDRO-5H-PYRROLO(1,2-C)IMIDAZOL-5-YL)-3-FLUORO-
Systematic Name English
OSILODROSTAT [USAN]
Common Name English
OSILODROSTAT [INN]
Common Name English
LCI699
Common Name English
4-((5R)-6,7-DIHYDRO-5H-PYRROLO(1,2-C)IMIDAZOL-5-YL)-3-FLUORO-BENZONITRILE
Systematic Name English
(+)-OSILODROSTAT
Common Name English
LCI699-NX
Code English
OSILODROSTAT [WHO-DD]
Common Name English
LCI-699
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 405113
Created by admin on Sat Jun 26 02:10:20 UTC 2021 , Edited by admin on Sat Jun 26 02:10:20 UTC 2021
NCI_THESAURUS C471
Created by admin on Sat Jun 26 02:10:20 UTC 2021 , Edited by admin on Sat Jun 26 02:10:20 UTC 2021
EU-Orphan Drug EU/3/14/1345
Created by admin on Sat Jun 26 02:10:20 UTC 2021 , Edited by admin on Sat Jun 26 02:10:20 UTC 2021
Code System Code Type Description
PUBCHEM
44139752
Created by admin on Sat Jun 26 02:10:20 UTC 2021 , Edited by admin on Sat Jun 26 02:10:20 UTC 2021
PRIMARY
DRUG BANK
DB11837
Created by admin on Sat Jun 26 02:10:20 UTC 2021 , Edited by admin on Sat Jun 26 02:10:20 UTC 2021
PRIMARY
INN
9818
Created by admin on Sat Jun 26 02:10:20 UTC 2021 , Edited by admin on Sat Jun 26 02:10:20 UTC 2021
PRIMARY
CAS
1304733-26-3
Created by admin on Sat Jun 26 02:10:20 UTC 2021 , Edited by admin on Sat Jun 26 02:10:20 UTC 2021
SUPERSEDED
NCI_THESAURUS
C131535
Created by admin on Sat Jun 26 02:10:20 UTC 2021 , Edited by admin on Sat Jun 26 02:10:20 UTC 2021
PRIMARY
RXCUI
2286252
Created by admin on Sat Jun 26 02:10:20 UTC 2021 , Edited by admin on Sat Jun 26 02:10:20 UTC 2021
PRIMARY
DRUG CENTRAL
5384
Created by admin on Sat Jun 26 02:10:20 UTC 2021 , Edited by admin on Sat Jun 26 02:10:20 UTC 2021
PRIMARY
CAS
928134-65-0
Created by admin on Sat Jun 26 02:10:20 UTC 2021 , Edited by admin on Sat Jun 26 02:10:20 UTC 2021
PRIMARY
FDA UNII
5YL4IQ1078
Created by admin on Sat Jun 26 02:10:20 UTC 2021 , Edited by admin on Sat Jun 26 02:10:20 UTC 2021
PRIMARY
Related Record Type Details
METABOLIC ENZYME -> INHIBITOR
WEAK INHIBITION
METABOLIC ENZYME -> INHIBITOR
WEAK INHIBITION
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> INHIBITOR
TIME-DEPENDENT INHIBITION
Ki
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
BINDER->LIGAND
BINDING
METABOLIC ENZYME -> SUBSTRATE
TARGET -> INHIBITOR
osilodrostat inhibited the activity of human CYP11B1 dose-dependently with IC50 values of 2.5 ± 0.1 nM (n = 4).
IC50
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> INHIBITOR
MODERATE INHIBITION
METABOLIC ENZYME -> INHIBITOR
WEAK INHIBITION
EXCRETED UNCHANGED
AMOUNT EXCRETED
URINE
SALT/SOLVATE -> PARENT
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC
Tmax PHARMACOKINETIC
blood-to-plasma ratio PHARMACOKINETIC