Details of the Drug

General Information of Drug (ID: DMRJLAT)

Drug Name

Osimertinib

Synonyms

Tagrisso

Indication

Disease Entry	ICD 11	Status	REF
Non-small-cell lung cancer	2C25.Y	Approved	[1]
Melanoma	2C30	Phase 3	[2], [3]

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

499.6

Topological Polar Surface Area (xlogp)

3.7

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 6 h [4]
Clearance: The oral clearance of drug is 14.2 L/h [5]
Half-life: The concentration or amount of drug in body reduced by one-half in 48 hours [6]
Metabolism: The drug is metabolized via the CYP3A and dealkylation [4]
Vd: The volume of distribution (Vd) of drug is 986 L [5]

Chemical Identifiers

Formula: C28H33N7O2
IUPAC Name: N-[2-[2-(dimethylamino)ethyl-methylamino]-4-methoxy-5-[[4-(1-methylindol-3-yl)pyrimidin-2-yl]amino]phenyl]prop-2-enamide
Canonical SMILES: CN1C=C(C2=CC=CC=C21)C3=NC(=NC=C3)NC4=C(C=C(C(=C4)NC(=O)C=C)N(C)CCN(C)C)OC
InChI: InChI=1S/C28H33N7O2/c1-7-27(36)30-22-16-23(26(37-6)17-25(22)34(4)15-14-33(2)3)32-28-29-13-12-21(31-28)20-18-35(5)24-11-9-8-10-19(20)24/h7-13,16-18H,1,14-15H2,2-6H3,(H,30,36)(H,29,31,32)
InChIKey: DUYJMQONPNNFPI-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 71496458
ChEBI ID: CHEBI:90943
CAS Number: 1421373-65-0
DrugBank ID: DB09330
TTD ID: D0O8GK
VARIDT ID: DR00655
ACDINA ID: D00495

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Epidermal growth factor receptor (EGFR)	TTGKNB4	EGFR_HUMAN	Inhibitor	[7]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease

Non-small-cell lung cancer

ICD Disease Classification

2C25.Y

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Epidermal growth factor receptor (EGFR)	DTT	EGFR	8.30E-26	0.06	0.13

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Osimertinib

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Brigatinib	DM7W94S	Moderate	Decreased metabolism of Osimertinib caused by Brigatinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[17]
Lurbinectedin	DMEFRTZ	Moderate	Decreased metabolism of Osimertinib caused by Lurbinectedin mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[18]
PF-06463922	DMKM7EW	Moderate	Increased metabolism of Osimertinib caused by PF-06463922 mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[19]
Pralsetinib	DMWU0I2	Moderate	Decreased metabolism of Osimertinib 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 Osimertinib and Selpercatinib.	Lung cancer [2C25]	[17]
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Coadministration of a Drug Treating the Disease Different from Osimertinib (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Ivosidenib	DM8S6T7	Major	Increased risk of prolong QT interval by the combination of Osimertinib and Ivosidenib.	Acute myeloid leukaemia [2A60]	[21]
Arn-509	DMT81LZ	Major	Increased metabolism of Osimertinib caused by Arn-509 mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[22]
Gilteritinib	DMWQ4MZ	Major	Increased risk of prolong QT interval by the combination of Osimertinib and Gilteritinib.	Acute myeloid leukaemia [2A60]	[19]
Oliceridine	DM6MDCF	Major	Increased risk of prolong QT interval by the combination of Osimertinib and Oliceridine.	Acute pain [MG31]	[23]
Levalbuterol	DM5YBO1	Moderate	Increased risk of ventricular arrhythmias by the combination of Osimertinib and Levalbuterol.	Asthma [CA23]	[24]
Troleandomycin	DMUZNIG	Major	Decreased metabolism of Osimertinib caused by Troleandomycin mediated inhibition of CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[19]
Ag-221	DMS0ZBI	Moderate	Decreased clearance of Osimertinib due to the transporter inhibition by Ag-221.	BCR-ABL1-negative chronic myeloid leukaemia [2A41]	[22]
Pexidartinib	DMS2J0Z	Moderate	Increased metabolism of Osimertinib caused by Pexidartinib mediated induction of CYP450 enzyme.	Bone/articular cartilage neoplasm [2F7B]	[19]
Talazoparib	DM1KS78	Moderate	Decreased clearance of Osimertinib due to the transporter inhibition by Talazoparib.	Breast cancer [2C60-2C6Y]	[25]
LY2835219	DM93VBZ	Moderate	Decreased metabolism of Osimertinib caused by LY2835219 mediated inhibition of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[17]
Tucatinib	DMBESUA	Major	Decreased metabolism of Osimertinib caused by Tucatinib mediated inhibition of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[19]
PF-04449913	DMSB068	Major	Increased risk of prolong QT interval by the combination of Osimertinib and PF-04449913.	Chronic myelomonocytic leukaemia [2A40]	[19]
Osilodrostat	DMIJC9X	Major	Increased risk of prolong QT interval by the combination of Osimertinib and Osilodrostat.	Cushing syndrome [5A70]	[19]
MK-8228	DMOB58Q	Moderate	Decreased metabolism of Osimertinib caused by MK-8228 mediated inhibition of CYP450 enzyme.	Cytomegaloviral disease [1D82]	[19]
Deutetrabenazine	DMUPFLI	Major	Increased risk of prolong QT interval by the combination of Osimertinib and Deutetrabenazine.	Dystonic disorder [8A02]	[19]
Ingrezza	DMVPLNC	Major	Increased risk of prolong QT interval by the combination of Osimertinib and Ingrezza.	Dystonic disorder [8A02]	[19]
Eslicarbazepine	DMZREFQ	Moderate	Increased metabolism of Osimertinib caused by Eslicarbazepine mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[19]
Bay 80-6946	DMLOS5R	Moderate	Decreased metabolism of Osimertinib caused by Bay 80-6946 mediated inhibition of CYP450 enzyme.	Follicular lymphoma [2A80]	[17]
Tazemetostat	DMWP1BH	Moderate	Increased metabolism of Osimertinib caused by Tazemetostat mediated induction of CYP450 enzyme.	Follicular lymphoma [2A80]	[19]
Ripretinib	DM958QB	Moderate	Decreased clearance of Osimertinib due to the transporter inhibition by Ripretinib.	Gastrointestinal stromal tumour [2B5B]	[22]
Fostemsavir	DM50ILT	Major	Increased risk of prolong QT interval by the combination of Osimertinib and Fostemsavir.	Human immunodeficiency virus disease [1C60-1C62]	[19]
Berotralstat	DMWA2DZ	Major	Decreased clearance of Osimertinib due to the transporter inhibition by Berotralstat.	Innate/adaptive immunodeficiency [4A00]	[26]
IPI-145	DMWA24P	Moderate	Decreased metabolism of Osimertinib caused by IPI-145 mediated inhibition of CYP450 enzyme.	Mature B-cell leukaemia [2A82]	[19]
Arry-162	DM1P6FR	Moderate	Increased metabolism of Osimertinib caused by Arry-162 mediated induction of CYP450 enzyme.	Melanoma [2C30]	[22]
LGX818	DMNQXV8	Major	Increased risk of prolong QT interval by the combination of Osimertinib and LGX818.	Melanoma [2C30]	[19]
Rimegepant	DMHOAUG	Moderate	Decreased clearance of Osimertinib due to the transporter inhibition by Rimegepant.	Migraine [8A80]	[27]
Lasmiditan	DMXLVDT	Moderate	Decreased clearance of Osimertinib due to the transporter inhibition by Lasmiditan.	Migraine [8A80]	[28]
Siponimod	DM2R86O	Major	Increased risk of ventricular arrhythmias by the combination of Osimertinib and Siponimod.	Multiple sclerosis [8A40]	[22]
Ocrelizumab	DMEZ2KH	Moderate	Additive immunosuppressive effects by the combination of Osimertinib and Ocrelizumab.	Multiple sclerosis [8A40]	[29]
Ozanimod	DMT6AM2	Major	Increased risk of ventricular arrhythmias by the combination of Osimertinib and Ozanimod.	Multiple sclerosis [8A40]	[17]
Entrectinib	DMMPTLH	Major	Increased risk of prolong QT interval by the combination of Osimertinib and Entrectinib.	Non-small cell lung cancer [2C25]	[19]
Rucaparib	DM9PVX8	Major	Increased risk of prolong QT interval by the combination of Osimertinib and Rucaparib.	Ovarian cancer [2C73]	[19]
Triclabendazole	DMPWGBR	Major	Increased risk of prolong QT interval by the combination of Osimertinib and Triclabendazole.	Parasitic worm infestation [1F90]	[19]
Abametapir	DM2RX0I	Moderate	Decreased metabolism of Osimertinib caused by Abametapir mediated inhibition of CYP450 enzyme.	Pediculosis [1G00]	[30]
Macimorelin	DMQYJIR	Major	Increased risk of prolong QT interval by the combination of Osimertinib and Macimorelin.	Pituitary gland disorder [5A60-5A61]	[31]
Lefamulin	DME6G97	Major	Increased risk of prolong QT interval by the combination of Osimertinib and Lefamulin.	Pneumonia [CA40]	[32]
Relugolix	DMK7IWL	Major	Decreased clearance of Osimertinib due to the transporter inhibition by Relugolix.	Prostate cancer [2C82]	[33]
Darolutamide	DMV7YFT	Moderate	Decreased clearance of Osimertinib due to the transporter inhibition by Darolutamide.	Prostate cancer [2C82]	[34]
Anthrax vaccine	DM9GSWY	Moderate	Antagonize the effect of Osimertinib when combined with Anthrax vaccine.	Sepsis [1G40-1G41]	[35]
Voxelotor	DMCS6M5	Moderate	Decreased metabolism of Osimertinib caused by Voxelotor mediated inhibition of CYP450 enzyme.	Sickle-cell disorder [3A51]	[19]
Tedizolid	DMG2SKR	Moderate	Decreased clearance of Osimertinib due to the transporter inhibition by Tedizolid.	Skin and skin-structure infection [1F28-1G0Z]	[17]
Telotristat ethyl	DMDIYFZ	Moderate	Increased metabolism of Osimertinib caused by Telotristat ethyl mediated induction of CYP450 enzyme.	Small intestine developmental anomaly [DA90]	[17]
Larotrectinib	DM26CQR	Moderate	Increased metabolism of Osimertinib caused by Larotrectinib mediated induction of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[19]
LEE011	DMMX75K	Major	Increased risk of prolong QT interval by the combination of Osimertinib and LEE011.	Solid tumour/cancer [2A00-2F9Z]	[19]
Pitolisant	DM8RFNJ	Major	Increased risk of prolong QT interval by the combination of Osimertinib and Pitolisant.	Somnolence [MG42]	[19]
Fostamatinib	DM6AUHV	Moderate	Decreased metabolism of Osimertinib caused by Fostamatinib mediated inhibition of CYP450 enzyme.	Thrombocytopenia [3B64]	[36]
Lusutrombopag	DMH6IKO	Moderate	Decreased clearance of Osimertinib due to the transporter inhibition by Lusutrombopag.	Thrombocytopenia [3B64]	[37]
Elagolix	DMB2C0E	Moderate	Increased metabolism of Osimertinib caused by Elagolix mediated induction of CYP450 enzyme.	Uterine fibroid [2E86]	[19]
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⏷ Show the Full List of 48 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
Sodium stearyl fumarate	E00545	23665634	lubricant
Eisenoxyd	E00585	56841934	Colorant
Ferric hydroxide oxide yellow	E00539	23320441	Colorant
Ferric oxide black	E00522	16211978	Colorant
Ferrosoferric oxide	E00231	14789	Colorant
Hydroxypropyl cellulose	E00632	Not Available	Binding agent; Coating agent; Emulsifying agent; Film/Membrane-forming agent; Modified-release agent; Suspending agent; Viscosity-controlling agent
Polyethylene glycol 3350	E00652	Not Available	Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Polyvinyl alcohol	E00666	Not Available	Coating agent; Emulsion stabilizing agent; Film/Membrane-forming agent
Talc	E00520	16211421	Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Haematite red	E00236	14833	Colorant
Cellulose microcrystalline	E00698	Not Available	Adsorbent; Suspending agent; Diluent
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⏷ Show the Full List of 13 Pharmaceutical Excipients of This Drug

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Osimertinib 40 mg tablet	40 mg	Oral Tablet	Oral
Osimertinib 80 mg tablet	80 mg	Oral Tablet	Oral
Osimertinib Mesylate eq 40mg base tablet	eq 40mg base	Tablet	Oral
Osimertinib Mesylate eq 80mg base tablet	eq 80mg base	Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

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10	Gefitinib ('Iressa', ZD1839) and new epidermal growth factor receptor inhibitors. Br J Cancer. 2004 Feb 9;90(3):566-72.
11	Quantitative prediction of fold resistance for inhibitors of EGFR. Biochemistry. 2009 Sep 8;48(35):8435-48.
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13	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1797).
14	Boehringer Ingelheim. Product Development Pipeline. June 2 2009.
15	Synthesis and Src kinase inhibitory activity of a series of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-furyl-3-quinolinecarbonitriles. J Med Chem. 2006 Dec 28;49(26):7868-76.
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19	Product Information. Tagrisso (osimertinib). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
20	Product Information. Gavreto (pralsetinib). Blueprint Medicines Corporation, Cambridge, MA.
21	Product Information. Tibsovo (ivosidenib). Agios Pharmaceuticals, Cambridge, MA.
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23	Product Information. Olinvyk (oliceridine). Trevena Inc, Chesterbrook, PA.
24	Product Information. Arcapta Neohaler (indacaterol). Novartis Pharmaceuticals, East Hanover, NJ.
25	Product Information. Talzenna (talazoparib). Pfizer U.S. Pharmaceuticals Group, New York, NY.
26	Product Information. Orladeyo (berotralstat). BioCryst Pharmaceuticals Inc, Durham, NC.
27	Product Information. Nurtec ODT (rimegepant). Biohaven Pharmaceuticals, New Haven, CT.
28	Product Information. Reyvow (lasmiditan). Lilly, Eli and Company, Indianapolis, IN.
29	Product Information. Ocrevus (ocrelizumab). Genentech, South San Francisco, CA.
30	Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
31	Product Information. Macrilen (macimorelin). Aeterna Zentaris, Charleston, SC.
32	Product Information. Xenleta (lefamulin). Nabriva Therapeutics US, Inc., King of Prussia, PA.
33	Product Information. Orgovyx (relugolix). Myovant Sciences, Inc., Brisbane, CA.
34	Product Information. Nubeqa (darolutamide). Bayer HealthCare Pharmaceuticals Inc., Whippany, NJ.
35	CDC. Centers for Disease Control and Prevention/ "Recommendations of the advisory committtee on immunization practices (ACIP): use of vaccines and immune globulins in persons with altered immunocompetence." MMWR Morb Mortal Wkly Rep 42(RR-04) (1993): 1-18. [PMID: 20300058]
36	Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.
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