DGIdb - OSIMERTINIB Drug Record

OSIMERTINIB chembl:CHEMBL3353410 ApprovedAntineoplastic

Alternate Names:

AZD-9291
AZD-9291 FREE BASE
OSIMERTINIB
TAGRISSO
AZD9291
TAGRISSO®
MERELETINIB (OBSOLETE INN)
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
MERELETINIB
AZD 9291
chembl:CHEMBL3353410
drugbank:09330
pubchem.compound:71496458
chemidplus:1421373-65-0
rxcui:1721560

Drug Info:

Drug Categories	acrylates
FDA Approval	Non-small cell lung cancer (with EGFR T790M mutation)
Drug Class	Kinase Inhibitor
Drug Categories	antineoplastic and immunomodulating agents
Drug Categories	breast cancer resistance protein inhibitors
Drug Categories	cytochrome p-450 cyp1a2 inducers (strength unknown)
Drug Categories	cytochrome p-450 cyp3a inhibitors
Drug Categories	cytochrome p-450 cyp3a substrates
Drug Categories	cytochrome p-450 cyp3a4 inducers
Drug Categories	cytochrome p-450 cyp3a4 inducers (strength unknown)
Drug Categories	cytochrome p-450 cyp3a4 inhibitors
Drug Categories	cytochrome p-450 cyp3a4 inhibitors (weak)
Drug Categories	cytochrome p-450 cyp3a4 substrates
Drug Categories	cytochrome p-450 cyp3a4 substrates (strength unknown)
Drug Categories	cytochrome p-450 enzyme inducers
Drug Categories	cytochrome p-450 enzyme inhibitors
Drug Categories	cytochrome p-450 substrates
Drug Categories	kinase inhibitor
Drug Categories	narrow therapeutic index drugs
Drug Categories	p-glycoprotein substrates
Drug Categories	tyrosine kinase inhibitors

(10 More Sources)

Publications:

Cho JH et al., 2020, Osimertinib for Patients With Non-Small-Cell Lung Cancer Harboring Uncommon EGFR Mutations: A Multicenter, Open-Label, Phase II Trial (KCSG-LU15-09)., J Clin Oncol
Yosaatmadja et al., 2015, Binding mode of the breakthrough inhibitor AZD9291 to epidermal growth factor receptor revealed., J. Struct. Biol.
Bahcall et al., 2016, Acquired METD1228V Mutation and Resistance to MET Inhibition in Lung Cancer., Cancer Discov
Konduri et al., 2016, EGFR Fusions as Novel Therapeutic Targets in Lung Cancer., Cancer Discov
Starrett JH et al., 2020, Drug Sensitivity and Allele Specificity of First-Line Osimertinib Resistance <i>EGFR</i> Mutations., Cancer Res
Castellano GM et al., 2019, A Novel Acquired Exon 20 EGFR M766Q Mutation in Lung Adenocarcinoma Mediates Osimertinib Resistance but is Sensitive to Neratinib and Poziotinib., J Thorac Oncol
Niu et al., 2014, Novel agents and strategies for overcoming EGFR TKIs resistance., Exp Hematol Oncol
Cross et al., 2014, AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer., Cancer Discov
Mok et al., 2017, Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer., N. Engl. J. Med.
Jänne et al., 2015, AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer., N. Engl. J. Med.
Eberlein et al., 2015, Acquired Resistance to the Mutant-Selective EGFR Inhibitor AZD9291 Is Associated with Increased Dependence on RAS Signaling in Preclinical Models., Cancer Res.
Greig, 2016, Osimertinib: First Global Approval., Drugs
Nukaga et al., 2017, Amplification of EGFR Wild-Type Alleles in Non-Small Cell Lung Cancer Cells Confers Acquired Resistance to Mutation-Selective EGFR Tyrosine Kinase Inhibitors., Cancer Res.
Ichihara et al., 2017, SFK/FAK Signaling Attenuates Osimertinib Efficacy in Both Drug-Sensitive and Drug-Resistant Models of EGFR-Mutant Lung Cancer., Cancer Res.
Gallant et al., 2015, EGFR Kinase Domain Duplication (EGFR-KDD) Is a Novel Oncogenic Driver in Lung Cancer That Is Clinically Responsive to Afatinib., Cancer Discov
Ercan et al., 2015, EGFR Mutations and Resistance to Irreversible Pyrimidine-Based EGFR Inhibitors., Clin. Cancer Res.
Ou et al., 2016, High MET amplification level as a resistance mechanism to osimertinib (AZD9291) in a patient that symptomatically responded to crizotinib treatment post-osimertinib progression., Lung Cancer
Ortiz-Cuaran et al., 2016, Heterogeneous Mechanisms of Primary and Acquired Resistance to Third-Generation EGFR Inhibitors., Clin. Cancer Res.
Thress et al., 2015, Acquired EGFR C797S mutation mediates resistance to AZD9291 in non-small cell lung cancer harboring EGFR T790M., Nat. Med.
Sequist et al., 2016, Osimertinib Responses After Disease Progression in Patients Who Had Been Receiving Rociletinib., JAMA Oncol
Kobayashi et al., 2015, EGFR Exon 18 Mutations in Lung Cancer: Molecular Predictors of Augmented Sensitivity to Afatinib or Neratinib as Compared with First- or Third-Generation TKIs., Clin. Cancer Res.
Moores et al., 2016, A Novel Bispecific Antibody Targeting EGFR and cMet Is Effective against EGFR Inhibitor-Resistant Lung Tumors., Cancer Res.
Peters et al., 2017, Compound Uncommon EGFR Mutations in a Patient with Advanced NSCLC and Durable Response to Sequential EGFR Targeted Therapies., J Thorac Oncol
Ballard et al., 2016, Preclinical Comparison of Osimertinib with Other EGFR-TKIs in EGFR-Mutant NSCLC Brain Metastases Models, and Early Evidence of Clinical Brain Metastases Activity., Clin. Cancer Res.
Ninomiya K et al., 2018, MET or NRAS amplification is an acquired resistance mechanism to the third-generation EGFR inhibitor naquotinib., Sci Rep

OSIMERTINIB EGFR

Interaction Score: 2.26

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? False

PMIDs:
31825714 26522274 27694386 27102076 32193290 31254668 24410791 24893891 27959700 25923549 25870145 26729184 28202511 28416483 26286086 25948633 27393507 27252416 25939061 26720284 26206867 27216193 28343545 27435396

Sources:
OncoKB FDA PharmGKB JAX-CKB CIViC TTD DrugBank COSMIC MyCancerGenome GuideToPharmacology ChemblInteractions CGI
OSIMERTINIB MET

Interaction Score: 0.77

Interaction Types & Directionality:

n/a

Interaction Info:

Approval Status Preclinical

Response Type resistant

Evidence Type Actionable

PMIDs:
27694386 29386539 27393507 27252416

Sources:
OncoKB JAX-CKB CIViC CGI
OSIMERTINIB NRAS

Interaction Score: 0.47

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type non-small cell lung carcinoma

Response Type resistant

Approval Status Preclinical

PMIDs:
25870145

Sources:
JAX-CKB
OSIMERTINIB KRAS

Interaction Score: 0.25

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical

Indication/Tumor Type non-small cell lung carcinoma

PMIDs:
25870145 27252416

Sources:
JAX-CKB
OSIMERTINIB ERBB2

Interaction Score: 0.22

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type lung adenocarcinoma

Response Type resistant

Approval Status Preclinical

PMIDs:
27252416

Sources:
JAX-CKB CGI

DrugBank: DB09330
- Version: 5.1.7
Alternate Names:

OSIMERTINIB DrugBank Drug Name

1421373-65-0 CAS Number

Tagrisso Drug Brand

Drug Info:

Drug Type small molecule

Drug Groups approved

Drug Categories acids, acyclic

Publications:

Yosaatmadja et al., 2015, Binding mode of the breakthrough inhibitor AZD9291 to epidermal growth factor receptor revealed., J. Struct. Biol.
MyCancerGenome: OSIMERTINIB
- Version: 20-Jun-2017
Alternate Names:

TAGRISSO Trade Name

Drug Info:

Drug Class Kinase Inhibitor

FDA Approval Non-small cell lung cancer (with EGFR T790M mutation)

Publications:

JAX-CKB: Osimertinib

Version: 27-September-2017

Alternate Names:

Drug Info:

Publications:

Eberlein et al., 2015, Acquired Resistance to the Mutant-Selective EGFR Inhibitor AZD9291 Is Associated with Increased Dependence on RAS Signaling in Preclinical Models., Cancer Res.

Ichihara et al., 2017, SFK/FAK Signaling Attenuates Osimertinib Efficacy in Both Drug-Sensitive and Drug-Resistant Models of EGFR-Mutant Lung Cancer., Cancer Res.

JAX-CKB: AZD9291

Version: 27-September-2017

Alternate Names:

Drug Info:

Publications:

Eberlein et al., 2015, Acquired Resistance to the Mutant-Selective EGFR Inhibitor AZD9291 Is Associated with Increased Dependence on RAS Signaling in Preclinical Models., Cancer Res.

Ortiz-Cuaran et al., 2016, Heterogeneous Mechanisms of Primary and Acquired Resistance to Third-Generation EGFR Inhibitors., Clin. Cancer Res.

Bahcall et al., 2016, Acquired METD1228V Mutation and Resistance to MET Inhibition in Lung Cancer., Cancer Discov

CIViC: OSIMERTINIB

Version: 14-September-2020

Alternate Names:

Drug Info:

Publications:

Cho JH et al., 2020, Osimertinib for Patients With Non-Small-Cell Lung Cancer Harboring Uncommon EGFR Mutations: A Multicenter, Open-Label, Phase II Trial (KCSG-LU15-09)., J Clin Oncol

Starrett JH et al., 2020, Drug Sensitivity and Allele Specificity of First-Line Osimertinib Resistance <i>EGFR</i> Mutations., Cancer Res

Castellano GM et al., 2019, A Novel Acquired Exon 20 EGFR M766Q Mutation in Lung Adenocarcinoma Mediates Osimertinib Resistance but is Sensitive to Neratinib and Poziotinib., J Thorac Oncol

GuideToPharmacology: 223366052
- Version: 29-September-2020
Alternate Names:

OSIMERTINIB GuideToPharmacology Ligand Name

Drug Info:

Publications:
TTD: AZD9291
- Version: 2020.06.01
Alternate Names:

D0RT2C TTD Drug ID

Drug Info:

Publications:
ChemblDrugs: chembl:CHEMBL3353410
- Version: ChEMBL_27
Alternate Names:

Drug Info:

Publications:
PharmGKB: osimertinib
- Version: 18-August-2020
Alternate Names:

Drug Info:

Publications:
ChemblInteractions: CHEMBL3353410
- Version: chembl_23
Alternate Names:

Drug Info:

Publications:
CGI: Osimertinib
- Version: 27-September-2017
Alternate Names:

Drug Info:

Publications:
OncoKB: Osimertinib
- Version: 23-July-2020
Alternate Names:

Drug Info:

Publications:
FDA: Osimertinib
- Version: 04-September-2020
Alternate Names:

Drug Info:

Publications:
COSMIC: Osimertinib
- Version: 4-Sep-2020
Alternate Names:

Drug Info:

Publications:

Specific Action of the Ligand	Inhibition
Endogenous Drug?	False
Direct Interaction?	False

Approval Status	Preclinical
Response Type	resistant
Evidence Type	Actionable

Indication/Tumor Type	non-small cell lung carcinoma
Response Type	resistant
Approval Status	Preclinical

Indication/Tumor Type	lung adenocarcinoma
Response Type	resistant
Approval Status	Preclinical

OSIMERTINIB	DrugBank Drug Name
1421373-65-0	CAS Number
Tagrisso	Drug Brand

Drug Type	small molecule
Drug Groups	approved
Drug Categories	acids, acyclic

OSIMERTINIB Drug Record

OSIMERTINIB chembl:CHEMBL3353410 ApprovedAntineoplastic

Alternate Names:

Drug Info:

Publications:

OSIMERTINIB EGFR

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Specific Action of the Ligand Inhibition Endogenous Drug? False Direct Interaction? False

PMIDs: 31825714 26522274 27694386 27102076 32193290 31254668 24410791 24893891 27959700 25923549 25870145 26729184 28202511 28416483 26286086 25948633 27393507 27252416 25939061 26720284 26206867 27216193 28343545 27435396

Sources: OncoKB FDA PharmGKB JAX-CKB CIViC TTD DrugBank COSMIC MyCancerGenome GuideToPharmacology ChemblInteractions CGI

OSIMERTINIB MET

Interaction Types & Directionality: n/a

Interaction Info: Approval Status Preclinical Response Type resistant Evidence Type Actionable

PMIDs: 27694386 29386539 27393507 27252416

Sources: OncoKB JAX-CKB CIViC CGI

OSIMERTINIB NRAS

Interaction Types & Directionality: n/a

Interaction Info: Indication/Tumor Type non-small cell lung carcinoma Response Type resistant Approval Status Preclinical

PMIDs: 25870145

Sources: JAX-CKB

OSIMERTINIB KRAS

Interaction Types & Directionality: n/a

Interaction Info: Evidence Type Actionable Approval Status Preclinical Indication/Tumor Type non-small cell lung carcinoma

PMIDs: 25870145 27252416

Sources: JAX-CKB

OSIMERTINIB ERBB2

Interaction Types & Directionality: n/a

Interaction Info: Indication/Tumor Type lung adenocarcinoma Response Type resistant Approval Status Preclinical

PMIDs: 27252416

Sources: JAX-CKB CGI

DrugBank: DB09330

Alternate Names: OSIMERTINIB DrugBank Drug Name 1421373-65-0 CAS Number Tagrisso Drug Brand

Drug Info: Drug Type small molecule Drug Groups approved Drug Categories acids, acyclic

Publications: Yosaatmadja et al., 2015, Binding mode of the breakthrough inhibitor AZD9291 to epidermal growth factor receptor revealed., J. Struct. Biol.

MyCancerGenome: OSIMERTINIB

Alternate Names: TAGRISSO Trade Name

Drug Info: Drug Class Kinase Inhibitor FDA Approval Non-small cell lung cancer (with EGFR T790M mutation)

Publications:

JAX-CKB: Osimertinib

Alternate Names:

Drug Info:

JAX-CKB: AZD9291

Alternate Names:

Drug Info:

CIViC: OSIMERTINIB

Alternate Names:

Drug Info:

GuideToPharmacology: 223366052

Alternate Names: OSIMERTINIB GuideToPharmacology Ligand Name

Drug Info:

Publications:

TTD: AZD9291

Alternate Names: D0RT2C TTD Drug ID

Drug Info:

Publications:

ChemblDrugs: chembl:CHEMBL3353410

Alternate Names:

Drug Info:

Publications:

PharmGKB: osimertinib

Alternate Names:

Drug Info:

Publications:

ChemblInteractions: CHEMBL3353410

Alternate Names:

Drug Info:

Publications:

CGI: Osimertinib

Alternate Names:

Drug Info:

Publications:

OncoKB: Osimertinib

Alternate Names:

Drug Info:

Publications:

FDA: Osimertinib

Alternate Names:

Drug Info:

Publications:

COSMIC: Osimertinib

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? False

PMIDs:
31825714 26522274 27694386 27102076 32193290 31254668 24410791 24893891 27959700 25923549 25870145 26729184 28202511 28416483 26286086 25948633 27393507 27252416 25939061 26720284 26206867 27216193 28343545 27435396

Sources:
OncoKB FDA PharmGKB JAX-CKB CIViC TTD DrugBank COSMIC MyCancerGenome GuideToPharmacology ChemblInteractions CGI

Interaction Types & Directionality:

n/a

Interaction Info:

Approval Status Preclinical

Response Type resistant

Evidence Type Actionable

PMIDs:
27694386 29386539 27393507 27252416

Sources:
OncoKB JAX-CKB CIViC CGI

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type non-small cell lung carcinoma

Response Type resistant

Approval Status Preclinical

PMIDs:
25870145

Sources:
JAX-CKB

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical

Indication/Tumor Type non-small cell lung carcinoma

PMIDs:
25870145 27252416

Sources:
JAX-CKB

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type lung adenocarcinoma

Response Type resistant

Approval Status Preclinical

PMIDs:
27252416

Sources:
JAX-CKB CGI

Alternate Names:

OSIMERTINIB DrugBank Drug Name

1421373-65-0 CAS Number

Tagrisso Drug Brand

Drug Info:

Drug Type small molecule

Drug Groups approved

Drug Categories acids, acyclic

Publications:

Yosaatmadja et al., 2015, Binding mode of the breakthrough inhibitor AZD9291 to epidermal growth factor receptor revealed., J. Struct. Biol.

Alternate Names:

TAGRISSO Trade Name

Drug Info:

Drug Class Kinase Inhibitor

FDA Approval Non-small cell lung cancer (with EGFR T790M mutation)

Alternate Names:

OSIMERTINIB GuideToPharmacology Ligand Name

Alternate Names:

D0RT2C TTD Drug ID