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]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 499.6
Logarithm of the Partition Coefficient (xlogp) 3.7
Rotatable Bond Count (rotbonds) 10
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 7
ADMET Property
Absorption Tmax
The time to maximum plasma concentration (Tmax) is 6 h []
Clearance
The oral clearance of drug is 14.2 L/h []
Half-life
The concentration or amount of drug in body reduced by one-half in 48 hours [3]
Metabolism
The drug is metabolized via the CYP3A and dealkylation []
Vd
The volume of distribution (Vd) of drug is 986 L []
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
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
EGFR T790M mutant (EGFR T790M) TTZ04AF EGFR_HUMAN Inhibitor [4]
Epidermal growth factor receptor (EGFR) TTGKNB4 EGFR_HUMAN Inhibitor [4]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Alanine aminotransferase 1 (GPT) OTOXOA0Q ALAT1_HUMAN Protein Interaction/Cellular Processes [5]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Gene/Protein Processing [6]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Gene/Protein Processing [7]
Catalase (CAT) OTHEBX9R CATA_HUMAN Drug Response [7]
Epidermal growth factor receptor (EGFR) OTAPLO1S EGFR_HUMAN Gene/Protein Processing [7]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Post-Translational Modifications [8]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Post-Translational Modifications [8]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Protein Interaction/Cellular Processes [9]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Post-Translational Modifications [6]
Sequestosome-1 (SQSTM1) OTGY5D5J SQSTM_HUMAN Gene/Protein Processing [10]
Molecular Interaction Atlas (MIA) 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) 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] [11]
Lurbinectedin DMEFRTZ Moderate Decreased metabolism of Osimertinib caused by Lurbinectedin mediated inhibition of CYP450 enzyme. Lung cancer [2C25] [12]
PF-06463922 DMKM7EW Moderate Increased metabolism of Osimertinib caused by PF-06463922 mediated induction of CYP450 enzyme. Lung cancer [2C25] [13]
Pralsetinib DMWU0I2 Moderate Decreased metabolism of Osimertinib caused by Pralsetinib mediated inhibition of CYP450 enzyme. Lung cancer [2C25] [14]
Selpercatinib DMZR15V Major Increased risk of prolong QT interval by the combination of Osimertinib and Selpercatinib. Lung cancer [2C25] [11]
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] [15]
Arn-509 DMT81LZ Major Increased metabolism of Osimertinib caused by Arn-509 mediated induction of CYP450 enzyme. Acute myeloid leukaemia [2A60] [16]
Gilteritinib DMTI0ZO Major Increased risk of prolong QT interval by the combination of Osimertinib and Gilteritinib. Acute myeloid leukaemia [2A60] [13]
Oliceridine DM6MDCF Major Increased risk of prolong QT interval by the combination of Osimertinib and Oliceridine. Acute pain [MG31] [17]
Levalbuterol DM5YBO1 Moderate Increased risk of ventricular arrhythmias by the combination of Osimertinib and Levalbuterol. Asthma [CA23] [18]
Troleandomycin DMUZNIG Major Decreased metabolism of Osimertinib caused by Troleandomycin mediated inhibition of CYP450 enzyme. Bacterial infection [1A00-1C4Z] [13]
Ag-221 DMS0ZBI Moderate Decreased clearance of Osimertinib due to the transporter inhibition by Ag-221. BCR-ABL1-negative chronic myeloid leukaemia [2A41] [16]
Pexidartinib DMS2J0Z Moderate Increased metabolism of Osimertinib caused by Pexidartinib mediated induction of CYP450 enzyme. Bone/articular cartilage neoplasm [2F7B] [13]
Talazoparib DM1KS78 Moderate Decreased clearance of Osimertinib due to the transporter inhibition by Talazoparib. Breast cancer [2C60-2C6Y] [19]
LY2835219 DM93VBZ Moderate Decreased metabolism of Osimertinib caused by LY2835219 mediated inhibition of CYP450 enzyme. Breast cancer [2C60-2C6Y] [11]
Tucatinib DMBESUA Major Decreased metabolism of Osimertinib caused by Tucatinib mediated inhibition of CYP450 enzyme. Breast cancer [2C60-2C6Y] [13]
PF-04449913 DMSB068 Major Increased risk of prolong QT interval by the combination of Osimertinib and PF-04449913. Chronic myelomonocytic leukaemia [2A40] [13]
Osilodrostat DMIJC9X Major Increased risk of prolong QT interval by the combination of Osimertinib and Osilodrostat. Cushing syndrome [5A70] [13]
MK-8228 DMOB58Q Moderate Decreased metabolism of Osimertinib caused by MK-8228 mediated inhibition of CYP450 enzyme. Cytomegaloviral disease [1D82] [13]
Deutetrabenazine DMUPFLI Major Increased risk of prolong QT interval by the combination of Osimertinib and Deutetrabenazine. Dystonic disorder [8A02] [13]
Ingrezza DMVPLNC Major Increased risk of prolong QT interval by the combination of Osimertinib and Ingrezza. Dystonic disorder [8A02] [13]
Eslicarbazepine DMZREFQ Moderate Increased metabolism of Osimertinib caused by Eslicarbazepine mediated induction of CYP450 enzyme. Epilepsy/seizure [8A61-8A6Z] [13]
Bay 80-6946 DMLOS5R Moderate Decreased metabolism of Osimertinib caused by Bay 80-6946 mediated inhibition of CYP450 enzyme. Follicular lymphoma [2A80] [11]
Tazemetostat DMWP1BH Moderate Increased metabolism of Osimertinib caused by Tazemetostat mediated induction of CYP450 enzyme. Follicular lymphoma [2A80] [13]
Ripretinib DM958QB Moderate Decreased clearance of Osimertinib due to the transporter inhibition by Ripretinib. Gastrointestinal stromal tumour [2B5B] [16]
Fostemsavir DM50ILT Major Increased risk of prolong QT interval by the combination of Osimertinib and Fostemsavir. Human immunodeficiency virus disease [1C60-1C62] [13]
Berotralstat DMWA2DZ Major Decreased clearance of Osimertinib due to the transporter inhibition by Berotralstat. Innate/adaptive immunodeficiency [4A00] [20]
IPI-145 DMWA24P Moderate Decreased metabolism of Osimertinib caused by IPI-145 mediated inhibition of CYP450 enzyme. Mature B-cell leukaemia [2A82] [13]
Arry-162 DM1P6FR Moderate Increased metabolism of Osimertinib caused by Arry-162 mediated induction of CYP450 enzyme. Melanoma [2C30] [16]
LGX818 DMNQXV8 Major Increased risk of prolong QT interval by the combination of Osimertinib and LGX818. Melanoma [2C30] [13]
Rimegepant DMHOAUG Moderate Decreased clearance of Osimertinib due to the transporter inhibition by Rimegepant. Migraine [8A80] [21]
Lasmiditan DMXLVDT Moderate Decreased clearance of Osimertinib due to the transporter inhibition by Lasmiditan. Migraine [8A80] [22]
Siponimod DM2R86O Major Increased risk of ventricular arrhythmias by the combination of Osimertinib and Siponimod. Multiple sclerosis [8A40] [16]
Ocrelizumab DMEZ2KH Moderate Additive immunosuppressive effects by the combination of Osimertinib and Ocrelizumab. Multiple sclerosis [8A40] [23]
Ozanimod DMT6AM2 Major Increased risk of ventricular arrhythmias by the combination of Osimertinib and Ozanimod. Multiple sclerosis [8A40] [11]
Entrectinib DMMPTLH Major Increased risk of prolong QT interval by the combination of Osimertinib and Entrectinib. Non-small cell lung cancer [2C25] [13]
Rucaparib DM9PVX8 Major Increased risk of prolong QT interval by the combination of Osimertinib and Rucaparib. Ovarian cancer [2C73] [13]
Triclabendazole DMPWGBR Major Increased risk of prolong QT interval by the combination of Osimertinib and Triclabendazole. Parasitic worm infestation [1F90] [13]
Abametapir DM2RX0I Moderate Decreased metabolism of Osimertinib caused by Abametapir mediated inhibition of CYP450 enzyme. Pediculosis [1G00] [24]
Macimorelin DMQYJIR Major Increased risk of prolong QT interval by the combination of Osimertinib and Macimorelin. Pituitary gland disorder [5A60-5A61] [25]
Lefamulin DME6G97 Major Increased risk of prolong QT interval by the combination of Osimertinib and Lefamulin. Pneumonia [CA40] [26]
Relugolix DMK7IWL Major Decreased clearance of Osimertinib due to the transporter inhibition by Relugolix. Prostate cancer [2C82] [27]
Darolutamide DMV7YFT Moderate Decreased clearance of Osimertinib due to the transporter inhibition by Darolutamide. Prostate cancer [2C82] [28]
Anthrax vaccine DM9GSWY Moderate Antagonize the effect of Osimertinib when combined with Anthrax vaccine. Sepsis [1G40-1G41] [29]
Voxelotor DMCS6M5 Moderate Decreased metabolism of Osimertinib caused by Voxelotor mediated inhibition of CYP450 enzyme. Sickle-cell disorder [3A51] [13]
Tedizolid DMG2SKR Moderate Decreased clearance of Osimertinib due to the transporter inhibition by Tedizolid. Skin and skin-structure infection [1F28-1G0Z] [11]
Telotristat ethyl DMDIYFZ Moderate Increased metabolism of Osimertinib caused by Telotristat ethyl mediated induction of CYP450 enzyme. Small intestine developmental anomaly [DA90] [11]
Larotrectinib DM26CQR Moderate Increased metabolism of Osimertinib caused by Larotrectinib mediated induction of CYP450 enzyme. Solid tumour/cancer [2A00-2F9Z] [13]
LEE011 DMMX75K Major Increased risk of prolong QT interval by the combination of Osimertinib and LEE011. Solid tumour/cancer [2A00-2F9Z] [13]
Pitolisant DM8RFNJ Major Increased risk of prolong QT interval by the combination of Osimertinib and Pitolisant. Somnolence [MG42] [13]
Fostamatinib DM6AUHV Moderate Decreased metabolism of Osimertinib caused by Fostamatinib mediated inhibition of CYP450 enzyme. Thrombocytopenia [3B64] [30]
Lusutrombopag DMH6IKO Moderate Decreased clearance of Osimertinib due to the transporter inhibition by Lusutrombopag. Thrombocytopenia [3B64] [31]
Elagolix DMB2C0E Moderate Increased metabolism of Osimertinib caused by Elagolix mediated induction of CYP450 enzyme. Uterine fibroid [2E86] [13]
⏷ 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
⏷ 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

References

1 The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
2 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. (Ligand id: 7719).
3 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
4 AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov. 2014 Sep;4(9):1046-61.
5 Cytotoxicity of 34 FDA approved small-molecule kinase inhibitors in primary rat and human hepatocytes. Toxicol Lett. 2018 Jul;291:138-148. doi: 10.1016/j.toxlet.2018.04.010. Epub 2018 Apr 12.
6 Dihydromyricetin suppresses tumor growth via downregulation of the EGFR/Akt/survivin signaling pathway. J Biochem Mol Toxicol. 2023 Jun;37(6):e23328. doi: 10.1002/jbt.23328. Epub 2023 Feb 19.
7 Osimertinib induces autophagy and apoptosis via reactive oxygen species generation in non-small cell lung cancer cells. Toxicol Appl Pharmacol. 2017 Apr 15;321:18-26. doi: 10.1016/j.taap.2017.02.017. Epub 2017 Feb 22.
8 Dictamnine, a novel c-Met inhibitor, suppresses the proliferation of lung cancer cells by downregulating the PI3K/AKT/mTOR and MAPK signaling pathways. Biochem Pharmacol. 2022 Jan;195:114864. doi: 10.1016/j.bcp.2021.114864. Epub 2021 Nov 30.
9 Targeting the EMT transcription factor TWIST1 overcomes resistance to EGFR inhibitors in EGFR-mutant non-small-cell lung cancer. Oncogene. 2019 Jan;38(5):656-670. doi: 10.1038/s41388-018-0482-y. Epub 2018 Aug 31.
10 AZD9291 promotes autophagy and inhibits PI3K/Akt pathway in NSCLC cancer cells. J Cell Biochem. 2019 Jan;120(1):756-767. doi: 10.1002/jcb.27434. Epub 2018 Aug 26.
11 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
12 Product Information. Accolate (zafirlukast). Zeneca Pharmaceuticals, Wilmington, DE.
13 Product Information. Tagrisso (osimertinib). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
14 Product Information. Gavreto (pralsetinib). Blueprint Medicines Corporation, Cambridge, MA.
15 Product Information. Tibsovo (ivosidenib). Agios Pharmaceuticals, Cambridge, MA.
16 Cerner Multum, Inc. "Australian Product Information.".
17 Product Information. Olinvyk (oliceridine). Trevena Inc, Chesterbrook, PA.
18 Product Information. Arcapta Neohaler (indacaterol). Novartis Pharmaceuticals, East Hanover, NJ.
19 Product Information. Talzenna (talazoparib). Pfizer U.S. Pharmaceuticals Group, New York, NY.
20 Product Information. Orladeyo (berotralstat). BioCryst Pharmaceuticals Inc, Durham, NC.
21 Product Information. Nurtec ODT (rimegepant). Biohaven Pharmaceuticals, New Haven, CT.
22 Product Information. Reyvow (lasmiditan). Lilly, Eli and Company, Indianapolis, IN.
23 Product Information. Ocrevus (ocrelizumab). Genentech, South San Francisco, CA.
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. Xenleta (lefamulin). Nabriva Therapeutics US, Inc., King of Prussia, PA.
27 Product Information. Orgovyx (relugolix). Myovant Sciences, Inc., Brisbane, CA.
28 Product Information. Nubeqa (darolutamide). Bayer HealthCare Pharmaceuticals Inc., Whippany, NJ.
29 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]
30 Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.
31 EMA. European Medicines Agency. European Union "EMA - List of medicines under additional monitoring.".