Details of the Drug

General Information of Drug (ID: DMIJC9X)

Drug Name

Osilodrostat

Synonyms

LCI699; 928134-65-0; LCI-699; UNII-5YL4IQ1078; CHEMBL3099695; 5YL4IQ1078; Osilodrostat;4-[(5R)-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl]-3-fluorobenzonitrile; 1304733-26-3; Osilodrostat [USAN:INN]; LCI 699; Osilodrostat (USAN/INN); LCI699-NX; GTPL8310; SCHEMBL12460772; DTXSID40156570; MolPort-044-560-410; EX-A1397; ZINC72318114; s7456; BDBM50444549; AKOS027323750; DB11837; CS-6896; HY-16276; KB-78108; Z-3271; D11061; 4-[(5R)-6,7-Dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl]-3-fluorobenzo nitrile

Indication

Disease Entry	ICD 11	Status	REF
Cushing disease	5A70	Approved	[1]

Drug Type

Small molecular drug

Structure

3D MOL is unavailable

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

227.24

Topological Polar Surface Area (xlogp)

1.9

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Absorption Tmax: The time to maximum plasma concentration (Tmax) is 1 h [2]
Elimination: Following oral administration of radiolabeled osilodrostat, 90.6% of the radioactivity was eliminated in the urine with only 1.58% in the feces [2]
Half-life: The concentration or amount of drug in body reduced by one-half in 4 hours [2]
Metabolism: The drug is metabolized via plasma [3]
Vd: The volume of distribution (Vd) of drug is 100 L [2]

Chemical Identifiers

Formula: C13H10FN3
IUPAC Name: 4-[(5R)-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl]-3-fluorobenzonitrile
Canonical SMILES: C1CC2=CN=CN2[C@H]1C3=C(C=C(C=C3)C#N)F
InChI: 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
InChIKey: USUZGMWDZDXMDG-CYBMUJFWSA-N

Cross-matching ID

PubChem CID: 44139752
CAS Number: 928134-65-0
DrugBank ID: DB11837
TTD ID: D03AJU
ACDINA ID: D01304

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Steroid 11-beta-hydroxylase (CYP11B1)	TTIQUX7	C11B1_HUMAN	Modulator	[1]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Molecular Expression Atlas of This Drug

The Studied Disease

Cushing disease

ICD Disease Classification

5A70

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Steroid 11-beta-hydroxylase (CYP11B1)	DTT	CYP11B1	4.31E-04	-0.03	-0.13

Molecular Expression Atlas (MEA)

MEA Detail

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Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Osilodrostat (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Ivosidenib	DM8S6T7	Major	Increased risk of prolong QT interval by the combination of Osilodrostat and Ivosidenib.	Acute myeloid leukaemia [2A60]	[8]
Gilteritinib	DMWQ4MZ	Moderate	Increased risk of prolong QT interval by the combination of Osilodrostat and Gilteritinib.	Acute myeloid leukaemia [2A60]	[9]
Levalbuterol	DM5YBO1	Moderate	Increased risk of ventricular arrhythmias by the combination of Osilodrostat and Levalbuterol.	Asthma [CA23]	[10]
Troleandomycin	DMUZNIG	Major	Decreased metabolism of Osilodrostat caused by Troleandomycin mediated inhibition of CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[11]
LY2835219	DM93VBZ	Moderate	Decreased metabolism of Osilodrostat caused by LY2835219 mediated inhibition of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[12]
MK-8228	DMOB58Q	Moderate	Decreased metabolism of Osilodrostat caused by MK-8228 mediated inhibition of CYP450 enzyme.	Cytomegaloviral disease [1D82]	[13]
Deutetrabenazine	DMUPFLI	Moderate	Increased risk of prolong QT interval by the combination of Osilodrostat and Deutetrabenazine.	Dystonic disorder [8A02]	[14]
Ingrezza	DMVPLNC	Moderate	Increased risk of prolong QT interval by the combination of Osilodrostat and Ingrezza.	Dystonic disorder [8A02]	[13]
Eslicarbazepine	DMZREFQ	Moderate	Increased metabolism of Osilodrostat caused by Eslicarbazepine mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[11]
Tazemetostat	DMWP1BH	Moderate	Increased metabolism of Osilodrostat caused by Tazemetostat mediated induction of CYP450 enzyme.	Follicular lymphoma [2A80]	[15]
Avapritinib	DMK2GZX	Moderate	Decreased metabolism of Osilodrostat caused by Avapritinib mediated inhibition of CYP450 enzyme.	Gastrointestinal stromal tumour [2B5B]	[13]
MK-1439	DM215WE	Minor	Decreased metabolism of Osilodrostat caused by MK-1439 mediated inhibition of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[16]
Berotralstat	DMWA2DZ	Moderate	Decreased metabolism of Osilodrostat caused by Berotralstat mediated inhibition of CYP450 enzyme.	Innate/adaptive immunodeficiency [4A00]	[17]
Pemigatinib	DM819JF	Moderate	Decreased metabolism of Osilodrostat caused by Pemigatinib mediated inhibition of CYP450 enzyme.	Liver cancer [2C12]	[18]
Lurbinectedin	DMEFRTZ	Moderate	Decreased metabolism of Osilodrostat caused by Lurbinectedin mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[19]
PF-06463922	DMKM7EW	Moderate	Increased metabolism of Osilodrostat caused by PF-06463922 mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[11]
Pralsetinib	DMWU0I2	Moderate	Decreased metabolism of Osilodrostat caused by Pralsetinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[20]
Selpercatinib	DMZR15V	Major	Increased risk of prolong QT interval by the combination of Osilodrostat and Selpercatinib.	Lung cancer [2C25]	[21]
IPI-145	DMWA24P	Moderate	Decreased metabolism of Osilodrostat caused by IPI-145 mediated inhibition of CYP450 enzyme.	Mature B-cell leukaemia [2A82]	[18]
Siponimod	DM2R86O	Major	Increased risk of ventricular arrhythmias by the combination of Osilodrostat and Siponimod.	Multiple sclerosis [8A40]	[22]
Ozanimod	DMT6AM2	Major	Increased risk of ventricular arrhythmias by the combination of Osilodrostat and Ozanimod.	Multiple sclerosis [8A40]	[23]
Fedratinib	DM4ZBK6	Moderate	Decreased metabolism of Osilodrostat caused by Fedratinib mediated inhibition of CYP450 enzyme.	Myeloproliferative neoplasm [2A20]	[13]
Entrectinib	DMMPTLH	Moderate	Increased risk of prolong QT interval by the combination of Osilodrostat and Entrectinib.	Non-small cell lung cancer [2C25]	[13]
Rucaparib	DM9PVX8	Moderate	Decreased metabolism of Osilodrostat caused by Rucaparib mediated inhibition of CYP450 enzyme.	Ovarian cancer [2C73]	[13]
Triclabendazole	DMPWGBR	Moderate	Increased risk of prolong QT interval by the combination of Osilodrostat and Triclabendazole.	Parasitic worm infestation [1F90]	[8]
Abametapir	DM2RX0I	Moderate	Decreased metabolism of Osilodrostat caused by Abametapir mediated inhibition of CYP450 enzyme.	Pediculosis [1G00]	[24]
Macimorelin	DMQYJIR	Major	Increased risk of prolong QT interval by the combination of Osilodrostat and Macimorelin.	Pituitary gland disorder [5A60-5A61]	[25]
Lefamulin	DME6G97	Major	Increased risk of prolong QT interval by the combination of Osilodrostat and Lefamulin.	Pneumonia [CA40]	[8]
Relugolix	DMK7IWL	Moderate	Increased risk of prolong QT interval by the combination of Osilodrostat and Relugolix.	Prostate cancer [2C82]	[13]
Darolutamide	DMV7YFT	Minor	Decreased metabolism of Osilodrostat caused by Darolutamide mediated inhibition of CYP450 enzyme.	Prostate cancer [2C82]	[26]
Voxelotor	DMCS6M5	Moderate	Decreased metabolism of Osilodrostat caused by Voxelotor mediated inhibition of CYP450 enzyme.	Sickle-cell disorder [3A51]	[18]
Telotristat ethyl	DMDIYFZ	Moderate	Increased metabolism of Osilodrostat caused by Telotristat ethyl mediated induction of CYP450 enzyme.	Small intestine developmental anomaly [DA90]	[15]
Larotrectinib	DM26CQR	Moderate	Decreased metabolism of Osilodrostat caused by Larotrectinib mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[22]
Elagolix	DMB2C0E	Moderate	Increased metabolism of Osilodrostat caused by Elagolix mediated induction of CYP450 enzyme.	Uterine fibroid [2E86]	[15]
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⏷ Show the Full List of 34 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Mannitol	E00103	6251	Diluent; Flavoring agent; Lyophilization aid; Plasticizing agent; Tonicity agent
Carmellose sodium	E00625	Not Available	Disintegrant
Ferric hydroxide oxide yellow	E00539	23320441	Colorant
Ferrosoferric oxide	E00231	14789	Colorant
Hypromellose	E00634	Not Available	Coating agent
Magnesium stearate	E00208	11177	lubricant
Polyethylene glycol 4000	E00654	Not Available	Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Talc	E00520	16211421	Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Haematite red	E00236	14833	Colorant
Hydrophobic colloidal silica	E00285	24261	Anticaking agent; Emulsion stabilizing agent; Glidant; Suspending agent; Viscosity-controlling agent
Cellulose microcrystalline	E00698	Not Available	Adsorbent; Suspending agent; Diluent
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⏷ Show the Full List of 12 Pharmaceutical Excipients of This Drug

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Osilodrostat eq 10mg base tablet	eq 10mg base	Tablet	Oral
Osilodrostat eq 1mg base tablet	eq 1mg base	Tablet	Oral
Osilodrostat eq 5mg base tablet	eq 5mg base	Tablet	Oral

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References

1	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
2	FDA Approved Drug Products: Isturisa (osilodrostat) oral tablets
3	EMA Summary of Product Characteristics: Isturisa (osilodrostat) oral tablets
4	Synthesis, biological evaluation, and molecular modeling of 1-benzyl-1H-imidazoles as selective inhibitors of aldosterone synthase (CYP11B2). J Med Chem. 2010 Feb 25;53(4):1712-25.
5	Effects of 3-MeSO2-DDE and some CYP inhibitors on glucocorticoid steroidogenesis in the H295R human adrenocortical carcinoma cell line. Toxicol In Vitro. 2002 Apr;16(2):113-21.
6	Replacement of imidazolyl by pyridyl in biphenylmethylenes results in selective CYP17 and dual CYP17/CYP11B1 inhibitors for the treatment of prosta... J Med Chem. 2010 Aug 12;53(15):5749-58.
7	Synthesis and evaluation of (pyridylmethylene)tetrahydronaphthalenes/-indanes and structurally modified derivatives: potent and selective inhibitor... J Med Chem. 2005 Mar 10;48(5):1563-75.
8	Product Information. Fycompa (perampanel). Eisai Inc, Teaneck, NJ.
9	Product Information. Xospata (gilteritinib). Astellas Pharma US, Inc, Deerfield, IL.
10	Product Information. Arcapta Neohaler (indacaterol). Novartis Pharmaceuticals, East Hanover, NJ.
11	Product Information. Isturisa (osilodrostat). Recordati Rare Diseases Inc, Lebanon, NJ.
12	Product Information. Verzenio (abemaciclib). Lilly, Eli and Company, Indianapolis, IN.
13	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
14	Product Information. Austedo (deutetrabenazine). Teva Pharmaceuticals USA, North Wales, PA.
15	Product Information. Diabinese (chlorpropamide). Pfizer US Pharmaceuticals, New York, NY.
16	Product Information. Pifeltro (doravirine). Merck & Company Inc, Whitehouse Station, NJ.
17	Product Information. Orladeyo (berotralstat). BioCryst Pharmaceuticals Inc, Durham, NC.
18	Product Information. Accolate (zafirlukast). Zeneca Pharmaceuticals, Wilmington, DE.
19	Product Information. Zepzelca (lurbinectedin). Jazz Pharmaceuticals, Palo Alto, CA.
20	Product Information. Gavreto (pralsetinib). Blueprint Medicines Corporation, Cambridge, MA.
21	Product Information. Retevmo (selpercatinib). Lilly, Eli and Company, Indianapolis, IN.
22	Cerner Multum, Inc. "Australian Product Information.".
23	Product Information. Zeposia (ozanimod). Celgene Corporation, Summit, NJ.
24	Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
25	Product Information. Macrilen (macimorelin). Aeterna Zentaris, Charleston, SC.
26	Product Information. Nubeqa (darolutamide). Bayer HealthCare Pharmaceuticals Inc., Whippany, NJ.