Identification

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Name
Osimertinib
Accession Number
DB09330
Type
Small Molecule
Groups
Approved
Description

Osimertinib is an oral, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) drug developed by AstraZeneca Pharmaceuticals. Its use is indicated for the treatment of metastatic non-small cell lung cancer (NSCLC) in cases where tumour EGFR expression is positive for the T790M mutation as detected by FDA-approved testing and which has progressed following therapy with a first-generation EGFR tyrosine kinase inhibitor. Approximately 10% of patients with NSCLC have a rapid and clinically effective response to EGFR-TKIs due to the presence of specific activating EGFR mutations within the tumour cells. More specifically, deletions around the LREA motif in exon 19 and exon 21 L858R point mutations are correlated with response to therapy.

Development of third-generation EGFR-TKIs, such as osimertinib, has been in response to altered tumour resistance patterns following treatment and toxic side effects that impact patient quality of life. Treatment with first-generation EGFR-TKIs (gefitinib and erlotinib) has been associated with the development of resistance through activating mutations in the EGFR gene. Second-generation EGFR-TKIs (afatinib and dacomitinib) were then developed to be more potent inhibitors, although their use is associated with increased toxicity through nonspecific targeting of wild-type EGFR. In contrast, third-generation inhibitors are specific for the gate-keeper T790M mutations which increases ATP binding activity to EGFR and result in poor prognosis for late-stage disease. Furthermore, osimertinib has been shown to spare wild-type EGFR during therapy, thereby reducing non-specific binding and limiting toxicity.

Structure
Thumb
Synonyms
  • Mereletinib
  • N-(2-{[2-(dimethylamino)ethyl](methyl)amino}-4-methoxy-5-{[4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl]amino}phenyl)prop-2-enamide
  • Osimertinib
  • Osimertinibum
External IDs
AZD 9291 / AZD-9291 / AZD9291
Product Ingredients
IngredientUNIICASInChI Key
Osimertinib mesylateRDL94R2A161421373-66-1FUKSNUHSJBTCFJ-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
TagrissoTablet80 mgOralAstra Zeneca2016-07-19Not applicableCanada
TagrissoTablet, film coated80 1/1OralAstraZeneca Pharmaceuticals LP2015-11-13Not applicableUs
TagrissoTablet, film coated40 mgOralAstra Zeneca Ab2016-02-02Not applicableEu
TagrissoTablet40 mgOralAstra Zeneca2016-07-19Not applicableCanada
TagrissoTablet, film coated40 1/1OralAstraZeneca Pharmaceuticals LP2015-11-13Not applicableUs
TagrissoTablet, film coated80 mgOralAstra Zeneca Ab2016-02-02Not applicableEu
TagrissoTablet, film coated40 mgOralAstra Zeneca Ab2016-02-02Not applicableEu
TagrissoTablet, film coated80 mgOralAstra Zeneca Ab2016-02-02Not applicableEu
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories
UNII
3C06JJ0Z2O
CAS number
1421373-65-0
Weight
Average: 499.619
Monoisotopic: 499.269573331
Chemical Formula
C28H33N7O2
InChI Key
DUYJMQONPNNFPI-UHFFFAOYSA-N
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)
IUPAC Name
N-(2-{[2-(dimethylamino)ethyl](methyl)amino}-4-methoxy-5-{[4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl]amino}phenyl)prop-2-enamide
SMILES
COC1=C(NC2=NC=CC(=N2)C2=CN(C)C3=C2C=CC=C3)C=C(NC(=O)C=C)C(=C1)N(C)CCN(C)C

Pharmacology

Indication

Osimertinib is indicated for the 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.

Associated Conditions
Pharmacodynamics

A pharmacokinetic/pharmacodynamic analysis suggested a concentration-dependent QTc interval prolongation of 14 msec (upper bound of two-sided 90% CI: 16 msec) at a dose of osimertinib 80 mg.

Mechanism of action

Osimertinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that binds to certain mutant forms of EGFR (T790M, L858R, and exon 19 deletion) that predominate in non-small cell lung cancer (NSCLC) tumours following treatment with first-line EGFR-TKIs. As a third-generation tyrosine kinase inhibitor, osimertinib is specific for the gate-keeper T790M mutation which increases ATP binding activity to EGFR and results in poor prognosis for late-stage disease. Furthermore, osimertinib has been shown to spare wild-type EGFR during therapy, thereby reducing non-specific binding and limiting toxicity.

TargetActionsOrganism
AEpidermal growth factor receptor
inhibitor
Humans
Additional Data Available
Adverse Effects

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Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Blackbox Warnings

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Absorption

The median time to Cmax was found to be 6 hours.

Volume of distribution

The mean volume of distribution at steady state is 986 L.

Protein binding

Plasma protein binding is likely high due to its physiochemical properties.

Metabolism

Osimertinib is metabolized to at least two pharmacologically active metabolites, AZ7550 and AZ5104, that circulate at approximately 10% of the concentration of the parent compound. Biochemical assays have shown that AZ7550 has similar potency and efficacy to osimertinib, while AZ5104 is more potent against mutant and wild-type EGFR. The main metabolic pathways are oxidation (predominantly by CYP3A) and dealkylation.

Route of elimination

Osimertinib is primarily eliminated through excretion in the feces (68%), to a lesser extent through urine (14%), while only 2% is excreted unchanged.

Half life

The population estimated mean half-life is 48 hours.

Clearance

Oral clearance is 14.2 L/hr.

Toxicity

Across clinical trials, interstitial lung disease (ILD)/pneumonitis occurred in 3.3% of treated patients with 0.5% of these being fatal. There is also a change of QTc interval prolongation; electrocardiogram and electrolytes should be monitored in patients with a history or predisposition for QTc prolongation. Cardiomyopathy occurred in 1.4% of patients, therefore left ventricular ejection fraction (LVEF) should be measured at baseline and then every 3 months during treatment. Osimertinib can cause embryo-fetal toxicity, requiring female patients to take effective birth control during therapy and for 6 weeks after final dose.

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
(R)-warfarinThe serum concentration of (R)-warfarin can be decreased when it is combined with Osimertinib.
(S)-WarfarinThe metabolism of (S)-Warfarin can be increased when combined with Osimertinib.
3,5-diiodothyropropionic acidThe therapeutic efficacy of 3,5-diiodothyropropionic acid can be decreased when used in combination with Osimertinib.
3,5-DiiodotyrosineThe therapeutic efficacy of 3,5-Diiodotyrosine can be decreased when used in combination with Osimertinib.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be increased when combined with Osimertinib.
6-Deoxyerythronolide BThe metabolism of Osimertinib can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe serum concentration of 6-O-benzylguanine can be decreased when it is combined with Osimertinib.
7-ethyl-10-hydroxycamptothecinThe metabolism of Osimertinib can be decreased when combined with 7-ethyl-10-hydroxycamptothecin.
8-azaguanineThe serum concentration of 8-azaguanine can be decreased when it is combined with Osimertinib.
8-chlorotheophyllineThe serum concentration of 8-chlorotheophylline can be decreased when it is combined with Osimertinib.
Additional Data Available
  • Extended Description
    Extended Description

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  • Severity
    Severity

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  • Evidence Level
    Evidence Level

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Food Interactions
Not Available

References

Synthesis Reference

Finlay MR, Anderton M, Ashton S, Ballard P, Bethel PA, Box MR, Bradbury RH, Brown SJ, Butterworth S, Campbell A, Chorley C, Colclough N, Cross DA, Currie GS, Grist M, Hassall L, Hill GB, James D, James M, Kemmitt P, Klinowska T, Lamont G, Lamont SG, Martin N, McFarland HL, Mellor MJ, Orme JP, Perkins D, Perkins P, Richmond G, Smith P, Ward RA, Waring MJ, Whittaker D, Wells S, Wrigley GL: Discovery of a potent and selective EGFR inhibitor (AZD9291) of both sensitizing and T790M resistance mutations that spares the wild type form of the receptor. J Med Chem. 2014 Oct 23;57(20):8249-67. doi: 10.1021/jm500973a. Epub 2014 Oct 1. Pubmed

General References
  1. Xu M, Xie Y, Ni S, Liu H: The latest therapeutic strategies after resistance to first generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) in patients with non-small cell lung cancer (NSCLC). Ann Transl Med. 2015 May;3(7):96. doi: 10.3978/j.issn.2305-5839.2015.03.60. [PubMed:26015938]
  2. Tan CS, Gilligan D, Pacey S: Treatment approaches for EGFR-inhibitor-resistant patients with non-small-cell lung cancer. Lancet Oncol. 2015 Sep;16(9):e447-59. doi: 10.1016/S1470-2045(15)00246-6. [PubMed:26370354]
  3. Ayeni D, Politi K, Goldberg SB: Emerging Agents and New Mutations in EGFR-Mutant Lung Cancer. Clin Cancer Res. 2015 Sep 1;21(17):3818-20. doi: 10.1158/1078-0432.CCR-15-1211. Epub 2015 Jul 13. [PubMed:26169963]
  4. Yosaatmadja Y, Silva S, Dickson JM, Patterson AV, Smaill JB, Flanagan JU, McKeage MJ, Squire CJ: Binding mode of the breakthrough inhibitor AZD9291 to epidermal growth factor receptor revealed. J Struct Biol. 2015 Dec;192(3):539-44. doi: 10.1016/j.jsb.2015.10.018. Epub 2015 Nov 2. [PubMed:26522274]
  5. Greig SL: Osimertinib: First Global Approval. Drugs. 2016 Feb;76(2):263-73. doi: 10.1007/s40265-015-0533-4. [PubMed:26729184]
  6. Shea M, Costa DB, Rangachari D: Management of advanced non-small cell lung cancers with known mutations or rearrangements: latest evidence and treatment approaches. Ther Adv Respir Dis. 2016 Apr;10(2):113-29. doi: 10.1177/1753465815617871. Epub 2015 Nov 30. [PubMed:26620497]
  7. Liao BC, Lin CC, Yang JC: Second and third-generation epidermal growth factor receptor tyrosine kinase inhibitors in advanced nonsmall cell lung cancer. Curr Opin Oncol. 2015 Mar;27(2):94-101. doi: 10.1097/CCO.0000000000000164. [PubMed:25611025]
  8. Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, Harris PL, Haserlat SM, Supko JG, Haluska FG, Louis DN, Christiani DC, Settleman J, Haber DA: Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004 May 20;350(21):2129-39. Epub 2004 Apr 29. [PubMed:15118073]
  9. Cross DA, Ashton SE, Ghiorghiu S, Eberlein C, Nebhan CA, Spitzler PJ, Orme JP, Finlay MR, Ward RA, Mellor MJ, Hughes G, Rahi A, Jacobs VN, Red Brewer M, Ichihara E, Sun J, Jin H, Ballard P, Al-Kadhimi K, Rowlinson R, Klinowska T, Richmond GH, Cantarini M, Kim DW, Ranson MR, Pao W: AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov. 2014 Sep;4(9):1046-61. doi: 10.1158/2159-8290.CD-14-0337. Epub 2014 Jun 3. [PubMed:24893891]
External Links
PubChem Compound
71496458
PubChem Substance
310265210
ChemSpider
31042598
BindingDB
50029668
ChEBI
90943
ChEMBL
CHEMBL3353410
PharmGKB
PA166131626
HET
YY3
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Osimertinib
ATC Codes
L01XE35 — Osimertinib
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
PDB Entries
4zau
FDA label
Download (183 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingOtherAdvanced (Inoperable) Non Small Cell Lung Cancer / Advanced Non Small Cell Lung Cancer2
1Active Not RecruitingOtherCarcinoma, Non-Small-Cell Lung With EGFR Mutation Positive1
1Active Not RecruitingOtherLung Cancer Non-Small Cell Cancer (NSCLC)1
1Active Not RecruitingTreatmentAdvanced Non Small Cell Lung Cancer1
1Active Not RecruitingTreatmentEGFR Mutation Positive Advanced Non Small Cell Lung Cancer1
1Active Not RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)3
1Active Not RecruitingTreatmentTumors, Solid1
1CompletedBasic ScienceHealthy Volunteers2
1CompletedOtherTumors, Solid1
1CompletedTreatmentHealthy Volunteers1
1CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
1CompletedTreatmentOncology1
1Not Yet RecruitingTreatmentNon-Small Cell Lung Cancer With Mutation in Epidermal Growth Factor Receptor (Disorder)1
1RecruitingOtherLung Cancer Non-Small Cell Cancer (NSCLC)1
1RecruitingTreatmentAdvanced Lung Non-Squamous Non-Small Cell Carcinoma / EGFR Activating Mutation / EGFR Exon 19 Deletion Mutation / EGFR NP_005219.2:p.G719X / EGFR NP_005219.2:p.L858R / EGFR NP_005219.2:p.L861Q / EGFR NP_005219.2:p.T790M / Metastatic Lung Non-Squamous Non-Small Cell Carcinoma / Recurrent Non-Small Cell Lung Carcinoma / Stage III Lung Non-Small Cell Cancer AJCC v7 / Stage III Non-Small Cell Lung Cancer / Stage III Non-Small Cell Lung Cancer AJCC v7 / Stage IIIA Lung Non-Small Cell Cancer AJCC v7 / Stage IIIA Non-Small Cell Lung Cancer / Stage IIIA Non-Small Cell Lung Cancer AJCC v7 / Stage IIIB Lung Non-Small Cell Cancer AJCC v7 / Stage IIIb Non-small Cell Lung Cancer / Stage IIIB Non-Small Cell Lung Cancer AJCC v7 / Stage IV Lung Non-Small Cell Cancer AJCC v7 / Stage IV Non-Small Cell Lung Cancer / Stage IV Non-Small Cell Lung Cancer AJCC v71
1RecruitingTreatmentAdvanced Solid Tumors / Advanced Solid Tumors Cancer / Malignancies1
1RecruitingTreatmentEGFR Activating Mutation / EGFR Exon 19 Deletion Mutation / EGFR Exon 20 Insertion Mutation / EGFR NP_005219.2:p.G719X / EGFR NP_005219.2:p.L858R / EGFR NP_005219.2:p.L861Q / EGFR NP_005219.2:p.T790M / EGFR T790M Mutation Negative / Metastatic Lung Non-Small Cell Carcinoma / Progressive Disease / Recurrent Lung Non-Small Cell Carcinoma / Recurrent Non-Small Cell Lung Carcinoma / Stage IV Lung Non-Small Cell Cancer AJCC v7 / Stage IV Non-Small Cell Lung Cancer / Stage IV Non-Small Cell Lung Cancer AJCC v71
1RecruitingTreatmentEGFR Activating Mutation / EGFR Exon 19 Deletion Mutation / EGFR NP_005219.2:p.G719X / EGFR NP_005219.2:p.L858R / EGFR NP_005219.2:p.L861Q / EGFR T790M Mutation Negative / Recurrent Lung Non-Small Cell Carcinoma / Recurrent Non-Small Cell Lung Carcinoma / Stage III Lung Non-Small Cell Cancer AJCC v7 / Stage III Non-Small Cell Lung Cancer AJCC v7 / Stage IIIA Lung Non-Small Cell Cancer AJCC v7 / Stage IIIA Non-Small Cell Lung Cancer / Stage IIIA Non-Small Cell Lung Cancer AJCC v7 / Stage IIIB Lung Non-Small Cell Cancer AJCC v7 / Stage IIIb Non-small Cell Lung Cancer / Stage IIIB Non-Small Cell Lung Cancer AJCC v7 / Stage IV Lung Non-Small Cell Cancer AJCC v7 / Stage IV Non-Small Cell Lung Cancer / Stage IV Non-Small Cell Lung Cancer AJCC v71
1RecruitingTreatmentEGFR Gene Mutations / Lung Cancer Metastatic1
1RecruitingTreatmentEGFR Positive Non-small Cell Lung Cancer1
1RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)3
1RecruitingTreatmentLung Cancers2
1RecruitingTreatmentMetastatic Non-Small Cell Lung Cancer1
1, 2Active Not RecruitingTreatmentAdvanced (Inoperable) Non Small Cell Lung Cancer / Advanced Non Small Cell Lung Cancer1
1, 2Active Not RecruitingTreatmentEGFR Gene Mutations / Lung Cancer Non-Small Cell Cancer (NSCLC)1
1, 2Active Not RecruitingTreatmentEGFR-mutant Lung Cancers / Lung Cancer Non-Small Cell Cancer (NSCLC)1
1, 2Active Not RecruitingTreatmentEGFR-mutated NSCLC (Disorder)1
1, 2Active Not RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / Lung Cancers / NSCLC (Non-small Cell Lung Carcinoma)1
1, 2RecruitingTreatmentAdvanced Lung Carcinoma / EGFR Activating Mutation / EGFR Exon 19 Deletion Mutation / EGFR NP_005219.2:p.L858R / EGFR T790M Mutation Negative / Lung Non-Small Cell Carcinoma / Metastatic Lung Carcinoma / Stage IV Lung Cancer AJCC v8 / Stage IVA Lung Cancer AJCC v8 / Stage IVB Lung Cancer AJCC v81
1, 2RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)2
1, 2RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / Lung Cancers1
2Active Not RecruitingOtherLung Cancer Non-Small Cell Cancer (NSCLC)1
2Active Not RecruitingTreatmentEGFR Gene Mutations / Neoplasms, Lung1
2Active Not RecruitingTreatmentEGFR Mutation Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer1
2Active Not RecruitingTreatmentLocally Advanced or Metastatic NSCLC1
2Active Not RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)4
2Active Not RecruitingTreatmentLung Cancers / Targeted Therapy1
2Active Not RecruitingTreatmentNon Small Cell Lung Cancer Metastatic1
2CompletedTreatmentLocally Advanced or Metastatic Non Small Cell Lung Cancer Stage IIIb - IV1
2Enrolling by InvitationTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2Not Yet RecruitingTreatmentAdvanced Non-Small Cell Lung Cancer / EGFR T790M / Non-Small Cell Lung Cancer Stage IIIB2
2Not Yet RecruitingTreatmentEGFR Activating Mutation / Leptomeningeal Metastasis / Lung Cancer Non-Small Cell Cancer (NSCLC)1
2Not Yet RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2Not Yet RecruitingTreatmentLung Cancers1
2Not Yet RecruitingTreatmentMetastatic Non Small Cell Lung Cancer1
2RecruitingTreatmentAdenocarcinoma of the Lung / Neoplasms, Lung1
2RecruitingTreatmentAdenocarcinomas / Lung Cancer Non-Small Cell Cancer (NSCLC) / Squamous Cell Carcinoma (SCC)1
2RecruitingTreatmentAdvanced Malignant Neoplasm / Advanced Malignant Solid Neoplasm / Bladder Carcinoma / Carcinoma, Breast / Carcinoma, Colorectal / Carcinoma, Pancreatic / Cervical Carcinoma / Colon Carcinoma / Endometrial Carcinoma / Esophageal Carcinoma / Gastric Carcinoma / Gliomas / Head and Neck Carcinoma / Liver and Intrahepatic Bile Duct Carcinoma / Lung, Carcinoma / Malignant Lymphomas / Malignant Uterine Neoplasm / Melanoma / Ovarian Carcinoma / Plasma Cell Myeloma / Prostate Cancer / Rectal Carcinoma / Recurrent Bladder Carcinoma / Recurrent Breast Carcinoma / Recurrent Cervical Carcinoma / Recurrent Colon Carcinoma / Recurrent Colorectal Carcinoma / Recurrent Esophageal Carcinoma / Recurrent Gastric Carcinoma / Recurrent Gliomas / Recurrent Head and Neck Carcinoma / Recurrent Liver Carcinoma / Recurrent Lung Carcinoma / Recurrent Lymphoma / Recurrent Malignant Solid Neoplasm / Recurrent Melanoma / Recurrent Ovarian Carcinoma / Recurrent Pancreatic Carcinoma / Recurrent Plasma Cell Myeloma / Recurrent Prostate Carcinoma / Recurrent Rectal Carcinoma / Recurrent Skin Carcinoma / Recurrent Solid Neoplasm / Recurrent Thyroid Gland Carcinoma / Recurrent Uterine Corpus Carcinoma / Refractory Lymphomas / Refractory Malignant Neoplasm / Refractory Malignant Solid Neoplasm / Refractory Plasma Cell Myeloma / Renal Carcinoma / Skin Carcinoma / Solid Neoplasms / Thyroid Gland Carcinoma / Uterine Corpus Cancer1
2RecruitingTreatmentCancer, Advanced / EGFR Gene Mutations / Lung Cancer Non-Small Cell Cancer (NSCLC) / Metastatic Cancers1
2RecruitingTreatmentCarcinoma NOS1
2RecruitingTreatmentEGFR (Epidermal Growth Factor Receptor) Exon 19 Deletion Mutation / EGFR NP_005219.2:p.L858R / EGFR NP_005219.2:p.T790M / Stage I Non-Small Cell Lung Cancer / Stage I Non-Small Cell Lung Cancer AJCC (American Joint Committee on Cancer) v7 / Stage IA Non-small Cell Lung Cancer / Stage IA Non-Small Cell Lung Carcinoma AJCC v7 / Stage IB Non-small Cell Lung Cancer / Stage IB Non-Small Cell Lung Carcinoma AJCC v7 / Stage II Non-Small Cell Lung Cancer / Stage II Non-Small Cell Lung Cancer AJCC v7 / Stage IIA Non-small Cell Lung Cancer / Stage IIA Non-Small Cell Lung Carcinoma AJCC v7 / Stage IIB Non-small Cell Lung Cancer / Stage IIB Non-Small Cell Lung Carcinoma AJCC v7 / Stage IIIA Non-Small Cell Lung Cancer / Stage IIIA Non-Small Cell Lung Cancer AJCC v71
2RecruitingTreatmentEGFR Activating Mutation / EGFR Exon 19 Deletion Mutation / EGFR NP_005219.2:p.L858R / EGFR NP_005219.2:p.T790M / Lung Cancer Non-Small Cell Cancer (NSCLC) / Lung Carcinoma Metastatic in the Brain / Lung Non-Small Cell Carcinoma / Metastatic Malignant Neoplasm in the Brain / Recurrent Non-Small Cell Lung Carcinoma1
2RecruitingTreatmentEGFR Exon 19 Deletion Mutation / EGFR NP_005219.2:p.L858R / EGFR NP_005219.2:p.T790M / Lung Cancer Non-Small Cell Cancer (NSCLC) / Lung Non-Small Cell Carcinoma / Malignant Neoplasms of Respiratory and Intrathoracic Organs / Recurrent Lung Non-Small Cell Carcinoma / Stage IIIB Lung Cancer AJCC v8 / Stage IV Lung Cancer AJCC v8 / Stage IVA Lung Cancer AJCC v8 / Stage IVB Lung Cancer AJCC v81
2RecruitingTreatmentEGFR Gene Amplification / EGFR Gene Mutations / Glioblastomas / Recurrent Glioblastoma / Supratentorial Glioblastoma / TP53 wt Allele1
2RecruitingTreatmentEGFR T790M / Fdg-PET / Lung Cancer Non-Small Cell Cancer (NSCLC)1
2RecruitingTreatmentFailed Tyrosine Kinase Inhibitors / Non-Small Cell Lung Cancer With EGFR T790M Mutation / With Brain and/or Leptomeningeal Metastasis1
2RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)10
2RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / Non-Small Cell Lung Cancer With Mutation in Epidermal Growth Factor Receptor (Disorder)1
2RecruitingTreatmentLung Cancers2
2RecruitingTreatmentMetastatic Brain Tumors / Non-small Cell Lung Cancer (NSCLC), Stage IV1
2SuspendedTreatmentAdvanced Lung Carcinoma / Advanced Lung Non-Small Cell Carcinoma / EGFR Exon 20 Insertion Mutation / Recurrent Lung Non-Small Cell Carcinoma / Recurrent Non-Small Cell Lung Carcinoma / Stage IIIB Lung Non-Small Cell Cancer AJCC v7 / Stage IIIb Non-small Cell Lung Cancer / Stage IIIB Non-Small Cell Lung Cancer AJCC v7 / Stage IV Lung Non-Small Cell Cancer AJCC v7 / Stage IV Non-Small Cell Lung Cancer / Stage IV Non-Small Cell Lung Cancer AJCC v71
2, 3CompletedTreatmentProgression Free Survival1
3Active Not RecruitingTreatmentAnticancer Treatment1
3Active Not RecruitingTreatmentLocally Advanced or Metastatic EGFR T790M+ NSCLC1
3Active Not RecruitingTreatmentMetastatic Non-Small Cell Lung Cancer1
3Active Not RecruitingTreatmentStage IB-IIIA Non-small Cell Lung Carcinoma1
3CompletedOtherLung Cancers1
3CompletedTreatmentLung Cancers1
3Not Yet RecruitingTreatmentAZD9291 / EGFR-TKI Resistant Mutation / Lung Cancer Non-Small Cell Cancer (NSCLC) / Metastatic Brain Tumors1
3RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
3RecruitingTreatmentNon Small Cell Lung Cancer (Stage III)1
4RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
Not AvailableActive Not RecruitingNot AvailableLung Cancer Non-Small Cell Cancer (NSCLC)2
Not AvailableCompletedNot AvailableT790M Positive NSCLC Patients1
Not AvailableNo Longer AvailableNot AvailableEGFR T790M Mutation Positive NSCLC1
Not AvailableNot Yet RecruitingNot AvailableImmune-Related Adverse Events / Lung Cancer Non-Small Cell Cancer (NSCLC)1
Not AvailableRecruitingNot AvailableLung Cancer Non-Small Cell Cancer (NSCLC)1
Not AvailableRecruitingOtherLocally Advanced or Metastatic NSCLC1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral40 mg
TabletOral80 mg
Tablet, film coatedOral40 1/1
Tablet, film coatedOral40 mg
Tablet, film coatedOral80 1/1
Tablet, film coatedOral80 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US8946235No2015-02-032032-08-08Us
US9732058No2017-08-152032-07-25Us
US10183020No2019-01-222035-01-02Us
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

    Learn more

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0224 mg/mLALOGPS
logP4.47ALOGPS
logP4.49ChemAxon
logS-4.4ALOGPS
pKa (Strongest Acidic)13.64ChemAxon
pKa (Strongest Basic)8.87ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area87.55 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity150.32 m3·mol-1ChemAxon
Polarizability56.84 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as n-alkylindoles. These are compounds containing an indole moiety that carries an alkyl chain at the 1-position.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Indoles and derivatives
Sub Class
N-alkylindoles
Direct Parent
N-alkylindoles
Alternative Parents
Aminophenyl ethers / Methoxyanilines / Indoles / Phenoxy compounds / Methoxybenzenes / Anisoles / Dialkylarylamines / Alkyl aryl ethers / Aminopyrimidines and derivatives / N-methylpyrroles
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Substituents
N-alkylindole / Indole / Methoxyaniline / Aminophenyl ether / Anisole / Phenol ether / Tertiary aliphatic/aromatic amine / Dialkylarylamine / Aniline or substituted anilines / Phenoxy compound
show 27 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Ubiquitin protein ligase binding
Specific Function
Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TG...
Gene Name
EGFR
Uniprot ID
P00533
Uniprot Name
Epidermal growth factor receptor
Molecular Weight
134276.185 Da
References
  1. Yosaatmadja Y, Silva S, Dickson JM, Patterson AV, Smaill JB, Flanagan JU, McKeage MJ, Squire CJ: Binding mode of the breakthrough inhibitor AZD9291 to epidermal growth factor receptor revealed. J Struct Biol. 2015 Dec;192(3):539-44. doi: 10.1016/j.jsb.2015.10.018. Epub 2015 Nov 2. [PubMed:26522274]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
Inducer
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inducer
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Osimertinib FDA label [File]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da

Drug created on November 18, 2015 10:23 / Updated on November 14, 2019 16:36