OSILODROSTAT

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C13H10FN3
Molecular Weight	227.237
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

FC1=C(C=CC(=C1)C#N)[C@H]2CCC3=CN=CN23

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	227.237
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26542280
Curator's Comment: The description was created based on several sources, including 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

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Cytochrome P450 11B2 6 Target ID: CHEMBL2722 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24422519	Inhibitor 8504		0.2 nM [IC50]
Cytochrome P450 11B1 9 Target ID: CHEMBL1908 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24422519	Inhibitor 8504		2.9 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Cushing’s disease 13 Sources: https://clinicaltrials.gov/ct2/show/record/NCT02697734	Primary	Phase III 665	Unknown Approved Use Unknown
Adrenal adenoma 2 Sources: https://clinicaltrials.gov/ct2/show/NCT02468193	Primary	Phase II 1147	Unknown Approved Use Unknown
Adrenal carcinoma 2 Sources: https://clinicaltrials.gov/ct2/show/NCT02468193	Primary	Phase II 1147	Unknown Approved Use Unknown
Acth-independent macronodular adrenal hyperplasia 2 Sources: https://clinicaltrials.gov/ct2/show/NCT02468193	Primary	Phase II 1147	Unknown Approved Use Unknown
Primary pigmented nodular adrenocortical disease 2 Sources: https://clinicaltrials.gov/ct2/show/NCT02468193	Primary	Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
7.91 ng/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000ClinPharmR.pdf	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:		OSILODROSTAT plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
306 ng/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000ClinPharmR.pdf	30 mg 2 times / day multiple, oral dose: 30 mg route of administration: Oral experiment type: MULTIPLE co-administered:		OSILODROSTAT plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
38.6 ng × h/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000ClinPharmR.pdf	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:		OSILODROSTAT plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
1680 ng × h/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000ClinPharmR.pdf	30 mg 2 times / day multiple, oral dose: 30 mg route of administration: Oral experiment type: MULTIPLE co-administered:		OSILODROSTAT plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
63.6% OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000ClinPharmR.pdf	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:		OSILODROSTAT plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
63.6% OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000ClinPharmR.pdf	30 mg 2 times / day multiple, oral dose: 30 mg route of administration: Oral experiment type: MULTIPLE co-administered:		OSILODROSTAT plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
7 mg 2 times / day steady, oral Recommended Dose: 7 mg, 2 times / day Route: oral Route: steady Dose: 7 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212801s000lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000MedR.pdf	unhealthy, 19-70 years Health Status: unhealthy Age Group: 19-70 years Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212801s000lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000MedR.pdf	Disc. AE: Hypocortisolism... AEs leading to discontinuation/dose reduction: Hypocortisolism Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212801s000lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000MedR.pdf
7 mg 2 times / day steady, oral Recommended Dose: 7 mg, 2 times / day Route: oral Route: steady Dose: 7 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212801s000lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000MedR.pdf	unhealthy, 19-70 years Health Status: unhealthy Age Group: 19-70 years Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212801s000lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000MedR.pdf	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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212801s000lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000MedR.pdf
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: https://pubmed.ncbi.nlm.nih.gov/32730798/	unhealthy, 20-69 years Health Status: unhealthy Age Group: 20-69 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/32730798/	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: https://pubmed.ncbi.nlm.nih.gov/32730798/
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: https://www.ema.europa.eu/en/documents/assessment-report/isturisa-epar-public-assessment-report_en.pdf	healthy Health Status: healthy Sex: M Sources: https://www.ema.europa.eu/en/documents/assessment-report/isturisa-epar-public-assessment-report_en.pdf	Other AEs: Electrocardiogram QTc interval prolonged... Other AEs: Electrocardiogram QTc interval prolonged Sources: https://www.ema.europa.eu/en/documents/assessment-report/isturisa-epar-public-assessment-report_en.pdf
30 mg 2 times / day steady, oral Highest studied dose Dose: 30 mg, 2 times / day Route: oral Route: steady Dose: 30 mg, 2 times / day Sources: https://www.ema.europa.eu/en/documents/assessment-report/isturisa-epar-public-assessment-report_en.pdf https://pubmed.ncbi.nlm.nih.gov/32730798/	unhealthy Health Status: unhealthy Sex: M+F Sources: https://www.ema.europa.eu/en/documents/assessment-report/isturisa-epar-public-assessment-report_en.pdf https://pubmed.ncbi.nlm.nih.gov/32730798/	Sources: https://www.ema.europa.eu/en/documents/assessment-report/isturisa-epar-public-assessment-report_en.pdf https://pubmed.ncbi.nlm.nih.gov/32730798/
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: https://www.ema.europa.eu/en/documents/assessment-report/isturisa-epar-public-assessment-report_en.pdf	unhealthy Health Status: unhealthy Sex: M+F Sources: https://www.ema.europa.eu/en/documents/assessment-report/isturisa-epar-public-assessment-report_en.pdf	Sources: https://www.ema.europa.eu/en/documents/assessment-report/isturisa-epar-public-assessment-report_en.pdf
150 mg single, oral Studied dose Dose: 150 mg Route: oral Route: single Dose: 150 mg Sources: https://www.ema.europa.eu/en/documents/assessment-report/isturisa-epar-public-assessment-report_en.pdf	healthy Health Status: healthy Sex: M+F Sources: https://www.ema.europa.eu/en/documents/assessment-report/isturisa-epar-public-assessment-report_en.pdf	Other AEs: QT interval prolonged... Other AEs: QT interval prolonged (3.6%) Sources: https://www.ema.europa.eu/en/documents/assessment-report/isturisa-epar-public-assessment-report_en.pdf
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: https://www.ema.europa.eu/en/documents/assessment-report/isturisa-epar-public-assessment-report_en.pdf	unhealthy Health Status: unhealthy Sex: M+F Sources: https://www.ema.europa.eu/en/documents/assessment-report/isturisa-epar-public-assessment-report_en.pdf	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: https://www.ema.europa.eu/en/documents/assessment-report/isturisa-epar-public-assessment-report_en.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946 inhibitor 2252 inducer 1087	inhibitor 2438	substrate 1388 inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP11B1 10 CYP11B2 11 CYP1A2 2153 CYP2C19 2057 CYP2E1 1060 CYP2B6 926 OCT2 779 MATE1 415 MATE2 267 CYP2A6 879 P-gp 1741 OAT1 725 OAT3 747 OATP1B1 1079 OATP1B3 961 OCT1 620 BSEP 550 BCRP 910 MRP2 499 CYP2C8 1057 CYP3A4/5 296 UGT1A1 246 UGT2B7 197	P-gp 2052 MRP 9 CYP2B6 776 UGT1A4 399 UGT2B7 456 UGT2B10 131	CYP1A2 832 CYP2B6 669

Drug as perpetrator

Target	Modality	Activity	Metabolite
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	moderate [Ki 0.175 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	moderate [Ki 1 uM]
OAT3 749	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000PharmR.pdf#page=40 Page: 40.0	no [IC50 3.23 uM]	LXB168 2
OAT3 749	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000PharmR.pdf#page=40 Page: 40.0	no [IC50 45 uM]
OAT1 730	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000PharmR.pdf#page=40 Page: 40.0	no [IC50 >100 uM]
OCT1 656	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000PharmR.pdf#page=40 Page: 40.0	no [IC50 >100 uM]
BCRP 985	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000PharmR.pdf#page=40 Page: 40.0	no
BCRP 985	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000PharmR.pdf#page=40 Page: 40.0	no	LXB168 2
BSEP 554	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000PharmR.pdf#page=40 Page: 40.0	no
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000PharmR.pdf#page=41 Page: 41.0	no	LXB168 2
CYP2A6 911	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000PharmR.pdf#page=41 Page: 41.0	no
CYP2A6 911	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000PharmR.pdf#page=41 Page: 41.0	no	LXB168 2
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000PharmR.pdf#page=41 Page: 41.0	no	LXB168 2
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000PharmR.pdf#page=41 Page: 41.0	no	LXB168 2
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000PharmR.pdf#page=41 Page: 41.0	no	LXB168 2
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000PharmR.pdf#page=41 Page: 41.0	no	LXB168 2
CYP3A4/5 357	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000PharmR.pdf#page=41 Page: 41.0	no	LXB168 2
MATE2 267	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000PharmR.pdf#page=40 Page: 40.0	no	LXB168 2
MRP2 625	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000PharmR.pdf#page=40 Page: 40.0	no
MRP2 625	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000PharmR.pdf#page=40 Page: 40.0	no	LXB168 2
OATP1B1 1095	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000PharmR.pdf#page=40 Page: 40.0	no
OATP1B1 1095	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000PharmR.pdf#page=40 Page: 40.0	no	LXB168 2
OATP1B3 970	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000PharmR.pdf#page=40 Page: 40.0	no
OATP1B3 970	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000PharmR.pdf#page=40 Page: 40.0	no	LXB168 2
OCT1 656	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000PharmR.pdf#page=40 Page: 40.0	no	LXB168 2
OCT2 782	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000PharmR.pdf#page=40 Page: 40.0	no	LXB168 2
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000PharmR.pdf#page=40 Page: 40.0	no
UGT2B7 210	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000PharmR.pdf#page=41 Page: 41.0	no
UGT2B7 210	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000PharmR.pdf#page=41 Page: 41.0	no	LXB168 2
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	weak [Ki 2 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	weak [Ki 20 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	weak [Ki 3.25 uM]
CYP11B2 12	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000ClinPharmR.pdf#page=8 Page: 8.0	yes [IC50 0.7 uM]
UGT1A1 303	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000PharmR.pdf#page=41 Page: 41.0	yes [IC50 0.7 uM]	LXB168 2
OAT1 730	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000PharmR.pdf#page=40 Page: 40.0	yes [IC50 19.9 uM]	LXB168 2
UGT1A1 303	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000PharmR.pdf#page=41 Page: 41.0	yes [IC50 30 uM]
MATE2 267	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000ClinPharmR.pdf#page=40 Page: 40.0	yes [IC50 37.7 uM]
MATE1 416	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000ClinPharmR.pdf#page=40 Page: 40.0	yes [IC50 5.57 uM]
MATE1 416	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000PharmR.pdf#page=40 Page: 40.0	yes [IC50 67.6 uM]	LXB168 2
OCT2 782	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000ClinPharmR.pdf#page=40 Page: 40.0	yes [IC50 8.59 uM]
BSEP 554	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000PharmR.pdf#page=40 Page: 40.0	yes [IC50 >50 uM]	LXB168 2
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000PharmR.pdf#page=40 Page: 40.0	yes [IC50 >50 uM]	LXB168 2
CYP2E1 1146	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	yes [Ki 0.482 uM]
CYP2B6 1160	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	yes [Ki 10 uM]
CYP2B6 1160	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000ClinPharmR.pdf#page=51 Page: 51.0	yes [Ki 225 uM]	LXB168 2
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000ClinPharmR.pdf#page=51 Page: 51.0	yes [Ki 86.3 uM]	LXB168 2
CYP11B1 10	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000ClinPharmR.pdf#page=8 Page: 8.0	yes
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	yes
CYP2B6 1160	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	yes
CYP3A4 2633	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
MRP 9	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	no
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	no
CYP2D6 1388	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	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 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000ClinPharmR.pdf#page=9 Page: 9.0
CYP2B6 776	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	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 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000ClinPharmR.pdf#page=9 Page: 9.0
CYP3A4 1946	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	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 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000ClinPharmR.pdf#page=9 Page: 9.0
UGT1A4 399	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	yes
UGT2B10 131	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	yes
UGT2B7 456	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212801Orig1s000PharmR.pdf#page=31 Page: 31.0

Sourcing

Vendor/Aggregator	ID	URL
AA Blocks	AA00H1GZ	https://www.aablocks.com/goods/Goods/detail?id=AA00H1GZ
AbMole Bioscience	M5233	http://www.abmole.com/products/lci699.html
Achemtek	0102-014347	http://www.achemtek.com/928134-65-0
Ambinter	Amb24088170	http://www.ambinter.com/reference/24088170
Aurum Pharmatech LLC	Z-3271	http://www.Aurumpharmatech.com/Product/ProductDetails/Z_3271
BLD Pharm	BD00936116	http://www.bldpharm.com/products/P000906684.html
Chem Scene	CS-6896	http://www.chemscene.com/928134-65-0.html
Chemspace	CSSB00102420042	https://chem-space.com/CSSB00102420042
eNovation Chemicals	D548085	http://www.enovationchem.com/productDetails.asp?productID=D548085
eNovation Chemicals	Y0975639	https://www.enovationchem.com/ProductDetails.asp?ProductID=Y0975639
Excenen	EX-A1397	http://www.excenen.com/searchresultlist.php?id=928134-65-0
Hairui	OSXM016	http://www.hairuichem.com/en/product/928134-65-0.html
Lab Network	LN01345822	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01345822
MedChem Express	HY-16276	https://www.medchemexpress.com/Osilodrostat.html
Smolecule	S548884	http://www.smolecule.com/products/s548884
THE BioTek	bt-288287	https://www.thebiotek.com/product/inhibitors/bt-288287

PubMed

Title	Date	PubMed
Efficacy and safety of LCI699 for hypertension: a meta-analysis of randomized controlled trials and systematic review.	2015	25683946
Medical therapy for Cushing's disease: adrenal steroidogenesis inhibitors and glucocorticoid receptor blockers.	2015 Apr	25560275
Therapy of endocrine disease: steroidogenesis enzyme inhibitors in Cushing's syndrome.	2015 Jun	25637072
Medical treatment of Cushing disease: new targets, new hope.	2015 Mar	25732642

Patents

Sample Use Guides

In Vivo Use Guide

1, 5, 10, or 20 mg/day for 48-weeks

Route of Administration: Oral

In Vitro Use Guide

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 `Mon Mar 31 21:34:17 GMT 2025` Edited by `admin` on `Mon Mar 31 21:34:17 GMT 2025`
Record UNII	5YL4IQ1078
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

OSILODROSTAT

Official Name

English

osilodrostat [INN]

Preferred Name

English

Osilodrostat [WHO-DD]

Common 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

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

OSILODROSTAT [MI]

Common Name

English

LCI699-NX

Code

English

LCI-699

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C471