Drug Details

General Information of the Drug (ID: DR6823)
Name
Osimertinib
Synonyms
Tagrisso
    Click to Show/Hide
Molecular Type
Small molecule
Disease Lung cancer [ICD-11: 2C25] Approved [1]
Structure
Click to Download Mol
2D MOL

3D MOL

    Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product
Formula
C28H33N7O2
PubChem CID
71496458
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
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
CAS Number
CAS 1421373-65-0
GDSC
Osimertinib
TTD Drug ID
D0O8GK
DrugBank ID
DB09330
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Natural Product(s) Able to Enhance the Efficacy of This Drug
          Pterostilbene      Vitis vinifera     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Phosphorylation CDCP1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation STAT3  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation YAP1  Molecule Info 
Pathway MAP
                    In-vitro Model MDA-MB-231 CVCL_0062 Breast adenocarcinoma Homo sapiens
PC-9 CVCL_B260 Lung adenocarcinoma Homo sapiens
NCI-H1975 CVCL_1511 Lung adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 The combination of osimertinib and pterostilbene reversed the osimertinib-induced STAT3, YAP1, and CUB domain-containing protein-1 (CDCP1) phosphorylation and slightly suppressed Src phosphorylation in PC9 and H1975 cells.
          Shikonin      Lithospermum erythrorhizon     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression ATF-4  Molecule Info 
Pathway MAP
Up-regulation Phosphorylation EIF2S1  Molecule Info 
Pathway MAP
                    Biological
                    Regulation		 Up-regulation ROS generation
                    In-vitro Model A-549 CVCL_0023 Lung adenocarcinoma Homo sapiens
NCI-H1299 CVCL_0060 Lung large cell carcinoma Homo sapiens
NCI-H460 CVCL_0459 Lung large cell carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Shikonin increased the anticancer activity of AZD9291 in primary wtEGFR NSCLC cells through ROS-mediated ER stress.
    β. A List of Natural Product(s) Able to Reverse the Resistance of This Drug
          Bufalin      Bufo gargarizans     Click to Show/Hide the Molecular Data of This NP
                 Reversing Drug Resistance     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [4]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression MCL1  Molecule Info 
Pathway MAP
                    In-vitro Model HCC827 CVCL_2063 Lung adenocarcinoma Homo sapiens
PC-9 CVCL_B260 Lung adenocarcinoma Homo sapiens
                    In-vivo Model Male BALB/c nude mice (4-6 weeks old, 18-22 g) were injected subcutaneously in the rear flank with 4 * 106 PC-9OR cells.
                    Experimental
                    Result(s)		 Degradation of MCL-1 by bufalin reverses acquired resistance to osimertinib in EGFR-mutant lung cancer.
          Honokiol      Magnolia officinalis     Click to Show/Hide the Molecular Data of This NP
                 Reversing Drug Resistance     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [5]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression MCL1  Molecule Info 
Pathway MAP
                    In-vitro Model PC-9 CVCL_B260 Lung adenocarcinoma Homo sapiens
HCC827 CVCL_2063 Lung adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Overcoming acquired resistance of EGFR-mutant NSCLC cells to the third generation EGFR inhibitor, osimertinib, with the natural product honokiol.
References
Reference 1 The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
Reference 2 Osimertinib and pterostilbene in EGFR-mutation-positive non-small cell lung cancer (NSCLC). Int J Biol Sci. 2019 Sep 7;15(12):2607-2614.
Reference 3 A natural anthraquinone derivative shikonin synergizes with AZD9291 against wtEGFR NSCLC cells through reactive oxygen species-mediated endoplasmic reticulum stress. Phytomedicine. 2020 Mar;68:153189.
Reference 4 Degradation of MCL-1 by bufalin reverses acquired resistance to osimertinib in EGFR-mutant lung cancer. Toxicol Appl Pharmacol. 2019 Sep 15;379:114662.
Reference 5 Overcoming acquired resistance of EGFR-mutant NSCLC cells to the third generation EGFR inhibitor, osimertinib, with the natural product honokiol. Mol Oncol. 2020 Apr;14(4):882-895.
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link