osimertinib Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
tyrosine kinase inhibitors 5062 1421373-65-0

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • osimertinib
  • tagrisso
  • AZD9291
  • AZD-9291
  • AZD 9291
  • osimertinib mesylate
  • osimertinib mesilate
  • AZD9291 mesylate
  • mereletinib
Osimertinib is a kinase inhibitor of the epidermal growth factor receptor (EGFR), which binds irreversibly to certain mutant forms of EGFR (T790M, L858R, and exon 19 deletion) at approximately 9-fold lower concentrations than wild-type. In cultured cells and animal tumor implantation models, osimertinib exhibited anti-tumor activity against NSCLC lines harboring EGFR-mutations (T790M/L858R, L858R, T790M/exon 19 deletion, and exon 19 deletion) and, to a lesser extent, wild-type EGFR amplifications.
  • Molecular weight: 499.62
  • Formula: C28H33N7O2
  • CLOGP: 4.60
  • LIPINSKI: 0
  • HAC: 9
  • HDO: 2
  • TPSA: 87.55
  • ALOGS: -4.35
  • ROTB: 10

  • Status: ONP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

None

Approvals:

DateAgencyCompanyOrphan
Feb. 2, 2016 EMA AstraZeneca AB
Nov. 13, 2015 FDA ASTRAZENECA PHARMS

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Malignant neoplasm progression 1106.09 27.68 384 5626 64542 46615510
Interstitial lung disease 408.80 27.68 178 5832 53771 46626281
Drug resistance 401.78 27.68 130 5880 17238 46662814
Acquired gene mutation 358.10 27.68 63 5947 553 46679499
Death 326.26 27.68 298 5712 335250 46344802
Paronychia 204.60 27.68 57 5953 4509 46675543
Metastases to central nervous system 188.04 27.68 66 5944 11155 46668897
Hepatic function abnormal 114.31 27.68 65 5945 34356 46645696
Pneumonitis 111.76 27.68 60 5950 28360 46651692
Pleural effusion 108.78 27.68 88 5922 82864 46597188
EGFR gene mutation 104.19 27.68 18 5992 140 46679912
Metastases to meninges 99.94 27.68 27 5983 1900 46678152
Lung disorder 90.78 27.68 61 5949 43243 46636809
Metastases to bone 77.49 27.68 40 5970 17436 46662616
Decreased appetite 74.29 27.68 107 5903 193729 46486323
Malignant transformation 73.76 27.68 15 5995 300 46679752
Dermatitis acneiform 72.21 27.68 25 5985 4045 46676007
Platelet count decreased 72.14 27.68 76 5934 99948 46580104
Electrocardiogram QT prolonged 68.36 27.68 55 5955 51270 46628782
Diarrhoea 67.48 27.68 190 5820 559412 46120640
Lymphangiosis carcinomatosa 63.61 27.68 17 5993 1147 46678905
Cardiac failure 59.85 27.68 62 5948 79886 46600166
Disease progression 54.75 27.68 63 5947 91237 46588815
Metastases to lung 48.90 27.68 25 5985 10671 46669381
Radiation pneumonitis 48.62 27.68 14 5996 1243 46678809
Erythema multiforme 45.29 27.68 23 5987 9681 46670371
Rash 39.76 27.68 118 5892 356394 46323658
Metastases to liver 39.59 27.68 27 5983 19558 46660494
Pain 39.45 27.68 7 6003 476941 46203111
Pulmonary embolism 37.25 27.68 57 5953 108528 46571524
Off label use 36.15 27.68 119 5891 379722 46300330
Stomatitis 35.75 27.68 44 5966 68253 46611799
Liver disorder 35.52 27.68 33 5977 37213 46642839
Multiple-drug resistance 35.09 27.68 13 5997 2552 46677500
Neutrophil count decreased 33.04 27.68 34 5976 43392 46636660
Malignant pleural effusion 31.96 27.68 12 5998 2446 46677606
Metastasis 31.76 27.68 14 5996 4298 46675754
Drug ineffective 30.10 27.68 26 5984 677812 46002240
Pulmonary alveolar haemorrhage 29.01 27.68 13 5997 4149 46675903
Metastases to lymph nodes 28.87 27.68 15 5995 6616 46673436
Ejection fraction decreased 27.70 27.68 21 5989 17916 46662136

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Malignant neoplasm progression 628.03 31.67 243 2751 72044 29877440
Drug resistance 298.16 31.67 101 2893 20032 29929452
Acquired gene mutation 241.70 31.67 48 2946 1113 29948371
Interstitial lung disease 229.33 31.67 114 2880 60083 29889401
Metastases to central nervous system 154.15 31.67 48 2946 7236 29942248
EGFR gene mutation 124.52 31.67 19 2975 81 29949403
Death 112.19 31.67 156 2838 357127 29592357
Pneumonitis 95.34 31.67 49 2945 27405 29922079
Metastases to meninges 92.88 31.67 22 2972 1177 29948307
Paronychia 85.89 31.67 25 2969 2986 29946498
Hepatic function abnormal 68.67 31.67 46 2948 41899 29907585
Lung disorder 60.03 31.67 38 2956 31431 29918053
Metastases to bone 44.71 31.67 21 2973 9637 29939847
Lymphangiosis carcinomatosa 41.87 31.67 11 2983 898 29948586
Radiation pneumonitis 41.53 31.67 13 2981 1983 29947501
Dermatitis acneiform 41.37 31.67 17 2977 5672 29943812
Liver disorder 37.89 31.67 28 2966 29694 29919790
Metastases to lung 36.02 31.67 17 2977 7878 29941606
Pulmonary embolism 34.98 31.67 41 2953 78094 29871390
Decreased appetite 31.77 31.67 55 2939 149855 29799629

Pharmacologic Action:

SourceCodeDescription
ATC L01EB04 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
PROTEIN KINASE INHIBITORS
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors
FDA MoA N0000175082 Kinase Inhibitors
FDA EPC N0000175605 Kinase Inhibitor
MeSH PA D000970 Antineoplastic Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D047428 Protein Kinase Inhibitors
FDA MoA N0000185506 Cytochrome P450 3A4 Inducers
FDA MoA N0000190113 Breast Cancer Resistance Protein Inhibitors
FDA MoA N0000190114 Cytochrome P450 3A Inhibitors
FDA MoA N0000191266 Cytochrome P450 1A2 Inducers
CHEBI has role CHEBI:35610 cytostatic
CHEBI has role CHEBI:74440 egfr inhibitor

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Non-small cell lung cancer, positive for epidermal growth factor receptor expression indication 426964009

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 10.64 acidic
pKa2 7.93 Basic
pKa3 5.6 Basic
pKa4 1.32 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
EQ 40MG BASE TAGRISSO ASTRAZENECA N208065 Nov. 13, 2015 RX TABLET ORAL April 18, 2021 TO ALLOW FOR FIRST-LINE TREATMENT OF PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WHOSE TUMORS HAVE EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) EXON 19 DELETIONS OR EXON 21 (L858R) SUBSTITUTION MUTATIONS, AS DETECTED BY AN FDA APPROVED TEST
EQ 80MG BASE TAGRISSO ASTRAZENECA N208065 Nov. 13, 2015 RX TABLET ORAL April 18, 2021 TO ALLOW FOR FIRST-LINE TREATMENT OF PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WHOSE TUMORS HAVE EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) EXON 19 DELETIONS OR EXON 21 (L858R) SUBSTITUTION MUTATIONS, AS DETECTED BY AN FDA APPROVED TEST
EQ 40MG BASE TAGRISSO ASTRAZENECA N208065 Nov. 13, 2015 RX TABLET ORAL Nov. 13, 2022 FOR TREATMENT OF PATIENTS WITH METASTATIC EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) T790M MUTATION-POSITIVE NON-SMALL CELL LUNG CANCER (NSCLC), AS DETECTED BY AN FDA-APPROVED TEST, WHO HAVE PROGRESSED ON OR AFTER EGFR TKI THERAPY
EQ 80MG BASE TAGRISSO ASTRAZENECA N208065 Nov. 13, 2015 RX TABLET ORAL Nov. 13, 2022 FOR TREATMENT OF PATIENTS WITH METASTATIC EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) T790M MUTATION-POSITIVE NON-SMALL CELL LUNG CANCER (NSCLC), AS DETECTED BY AN FDA-APPROVED TEST, WHO HAVE PROGRESSED ON OR AFTER EGFR TKI THERAPY
EQ 40MG BASE TAGRISSO ASTRAZENECA N208065 Nov. 13, 2015 RX TABLET ORAL Dec. 18, 2023 INDICATION OF OSIMERTINIB AS ADJUVANT THERAPY AFTER TUMOR RESECTION IN ADULT PATIENTS WITH NON-SMALL CELL LUNG CANCER (NSCLC) WHOSE TUMORS HAVE EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) EXON 19 DELETIONS OR EXON 21 L858R MUTATIONS, AS DETECTED BY AN FDA-APPROVED TEST
EQ 80MG BASE TAGRISSO ASTRAZENECA N208065 Nov. 13, 2015 RX TABLET ORAL Dec. 18, 2023 INDICATION OF OSIMERTINIB AS ADJUVANT THERAPY AFTER TUMOR RESECTION IN ADULT PATIENTS WITH NON-SMALL CELL LUNG CANCER (NSCLC) WHOSE TUMORS HAVE EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) EXON 19 DELETIONS OR EXON 21 L858R MUTATIONS, AS DETECTED BY AN FDA-APPROVED TEST
EQ 40MG BASE TAGRISSO ASTRAZENECA N208065 Nov. 13, 2015 RX TABLET ORAL April 18, 2025 INDICATED FOR THE FIRST-LINE TREATMENT OF PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WHOSE TUMORS HAVE EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) EXON 19 DELETIONS OR EXON 21 L858R MUTATIONS, AS DETECTED BY AN FDA-APPROVED TEST
EQ 80MG BASE TAGRISSO ASTRAZENECA N208065 Nov. 13, 2015 RX TABLET ORAL April 18, 2025 INDICATED FOR THE FIRST-LINE TREATMENT OF PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WHOSE TUMORS HAVE EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) EXON 19 DELETIONS OR EXON 21 L858R MUTATIONS, AS DETECTED BY AN FDA-APPROVED TEST
EQ 40MG BASE TAGRISSO ASTRAZENECA N208065 Nov. 13, 2015 RX TABLET ORAL Dec. 18, 2027 FOR ADJUVANT THERAPY AFTER TUMOR RESECTION IN ADULT PATIENTS WITH NON-SMALL CELL LUNG CANCER (NSCLC) WHOSE TUMORS HAVE EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) EXON 19 DELETIONS OR EXON 21 L858R MUTATIONS, AS DETECTED BY AN FDA-APPROVED TEST
EQ 80MG BASE TAGRISSO ASTRAZENECA N208065 Nov. 13, 2015 RX TABLET ORAL Dec. 18, 2027 FOR ADJUVANT THERAPY AFTER TUMOR RESECTION IN ADULT PATIENTS WITH NON-SMALL CELL LUNG CANCER (NSCLC) WHOSE TUMORS HAVE EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) EXON 19 DELETIONS OR EXON 21 L858R MUTATIONS, AS DETECTED BY AN FDA-APPROVED TEST

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Epidermal growth factor receptor Kinase INHIBITOR IC50 7.82 SCIENTIFIC LITERATURE DRUG LABEL
Insulin receptor Kinase IC50 6.04 CHEMBL
Potassium voltage-gated channel subfamily H member 2 Ion channel IC50 4.79 CHEMBL

External reference:

IDSource
1421373-66-1 SECONDARY_CAS_RN
4035124 VANDF
C3896906 UMLSCUI
CHEBI:90943 CHEBI
YY3 PDB_CHEM_ID
CHEMBL3353410 ChEMBL_ID
CHEMBL3545063 ChEMBL_ID
71496458 PUBCHEM_CID
DB09330 DRUGBANK_ID
C000596361 MESH_SUPPLEMENTAL_RECORD_UI
7719 IUPHAR_LIGAND_ID
10043 INN_ID
3C06JJ0Z2O UNII
1721559 RXNORM
237132 MMSL
31292 MMSL
d08397 MMSL
016583 NDDF
016584 NDDF
716032009 SNOMEDCT_US
734660003 SNOMEDCT_US
781312009 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
TAGRISSO HUMAN PRESCRIPTION DRUG LABEL 1 0310-1349 TABLET, FILM COATED 40 1 ORAL NDA 27 sections
TAGRISSO HUMAN PRESCRIPTION DRUG LABEL 1 0310-1350 TABLET, FILM COATED 80 1 ORAL NDA 27 sections