Drug Details
| General Information of the Drug (ID: DR6823) | ||||
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| Name |
Osimertinib
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| Synonyms |
Tagrisso
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| Molecular Type |
Small molecule
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| Disease | Lung cancer [ICD-11: 2C25] | Approved | [1] | |
| Structure |
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Click to Download Mol2D MOL |
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| 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
Metabolism
The drug is metabolized via the CYP3A and dealkylation
Vd
The volume of distribution (Vd) of drug is 986 L
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| Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product | ||||
| Formula |
C28H33N7O2
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| PubChem CID | ||||
| 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
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| 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)
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| InChIKey |
DUYJMQONPNNFPI-UHFFFAOYSA-N
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| CAS Number |
CAS 1421373-65-0
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| GDSC | ||||
| TTD Drug ID | ||||
| DrugBank ID | ||||
| Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally | ||||||
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| 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
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| Molecule(s)
Regulation |
Down-regulation | Phosphorylation | CDCP1 | Molecule Info | ||
| Down-regulation | Phosphorylation | STAT3 | Molecule Info |
Pathway MAP
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| Down-regulation | Phosphorylation | YAP1 | Molecule Info |
Pathway MAP
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| 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
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| Molecule(s)
Regulation |
Up-regulation | Expression | ATF-4 | Molecule Info |
Pathway MAP
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| Up-regulation | Phosphorylation | EIF2S1 | Molecule Info |
Pathway MAP
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| 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
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| Molecule(s)
Regulation |
Down-regulation | Expression | MCL1 | Molecule Info |
Pathway MAP
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| 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
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| Molecule(s)
Regulation |
Down-regulation | Expression | MCL1 | Molecule Info |
Pathway MAP
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| 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. | |||||
| Target and Pathway | ||||
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| Target(s) | Epidermal growth factor receptor (EGFR) | Molecule Info | ||
| Proto-oncogene c-Met (MET) | Molecule Info | |||
