Drug Details

General Information of the Drug (ID: DR8028)
Name
Erlotinib
Synonyms
Erlotinin; Tarceva; Erlotinib Base; OSI 744; R 1415; CP 358,774; CP-358774; Erlotinib(Tarceva); Tarceva (TN); CP-358,774; Erlotinib, OS-774; N-(3-ethynylphenyl)[6,7-bis(2-methoxyethoxy)quinazolin-4-yl]amine; N-(3-Ethynylphenyl)-6,7-bis(2-methoxyethoxy)-4-quinazolinamine; N-(3-Ethynylphenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine; N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)-4-Quinazolinamine; [6,7-BIS(2-METHOXY-ETHOXY)QUINAZOLINE-4-YL]-(3-ETHYNYLPHENYL)AMINE; [6,7-Bis-(2-methoxy-ethoxy)-quinazolin-4-yl]-(3-ethynyl-phenyl)-amine; 4-[(3-Ethynylphenyl)amino]-6,7-bis(2-methoxyethoxy)quinazoline; 4-[(3-ethynylphenyl)amino]-6,7-bis(2-methoxyethoxy)quinazoline
    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

ADMET Property
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability
Bioavailability
59% of drug becomes completely available to its intended biological destination(s)
Clearance
The drug present in the plasma can be removed from the body at the rate of 1.69 mL/min/kg
Elimination
0.3% of drug is excreted from urine in the unchanged form
Half-life
The concentration or amount of drug in body reduced by one-half in 36.2 hours
Metabolism
The drug is metabolized via the liver
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 5.446 micromolar/kg/day
Unbound Fraction
The unbound fraction of drug in plasma is 0.07%
Vd
The volume of distribution (Vd) of drug is 232 L
Water Solubility
The ability of drug to dissolve in water is measured as 0.4 mg/mL
    Click to Show/Hide
    Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product
Formula
C22H23N3O4
PubChem CID
176870
Canonical SMILES
COCCOC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC=CC(=C3)C#C)OCCOC
InChI
1S/C22H23N3O4/c1-4-16-6-5-7-17(12-16)25-22-18-13-20(28-10-8-26-2)21(29-11-9-27-3)14-19(18)23-15-24-22/h1,5-7,12-15H,8-11H2,2-3H3,(H,23,24,25)
InChIKey
AAKJLRGGTJKAMG-UHFFFAOYSA-N
CAS Number
CAS 183321-74-6
GDSC
Erlotinib
TTD Drug ID
D07POC
DrugBank ID
DB00530
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Natural Product(s) Able to Enhance the Efficacy of This Drug
          Atractylenolide 1      Atractylodes macrocephala     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 Expression CYB5R2  Molecule Info 
Pathway MAP
Down-regulation Expression EZH2  Molecule Info 
Pathway MAP
                    In-vitro Model NCI-H1299 CVCL_0060 Lung large cell carcinoma Homo sapiens
A-549 CVCL_0023 Lung adenocarcinoma Homo sapiens
                    In-vivo Model A549 cells, carrying the luciferase reporter gene (1x107 cells), were subcutaneously injectinto the mice.
                    Experimental
                    Result(s)		 Targeting the PDK1- and HOTAIR-mediated downstream molecule EZH2 by the combination of ATL-1 and erlotinib potentially facilitates the development of an additional novel strategy to combat lung cancer.
          Betulinic Acid      Rubus alceifolius     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		 Down-regulation Expression CDK6  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation RB1  Molecule Info 
Pathway MAP
Up-regulation Expression SQSTM1  Molecule Info 
Pathway MAP
Down-regulation Expression TYMS  Molecule Info 
Pathway MAP
                    Biological
                    Regulation		 Induction Loss of mitochondrial membrane potential
                    In-vitro Model HCC827 CVCL_2063 Lung adenocarcinoma Homo sapiens
NCI-H1975 CVCL_1511 Lung adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Combining betulinic acid with an EGFR TKI improves drug efficacy in EGFR TKI-resistant lung cancer cells.
          Capsaicin      Capsicum annuum     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 [4]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Phosphorylation AKT1  Molecule Info 
Pathway MAP
Down-regulation Expression ERCC1  Molecule Info 
Pathway MAP
                    In-vitro Model A-549 CVCL_0023 Lung adenocarcinoma Homo sapiens
NCI-H1975 CVCL_1511 Lung adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Capsaicin enhances erlotinib-induced cytotoxicity via AKT inactivation and excision repair cross-complementary 1 (ERCC1) down-regulation in human lung cancer cells.
          Cyclopamine      Veratrum californicum     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 [5]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression POU5F1  Molecule Info 
Pathway MAP
Down-regulation Expression PROM1  Molecule Info 
Pathway MAP
                    In-vitro Model Cells derived from glioblastoma patients Glioblastoma Homo sapiens
                    Experimental
                    Result(s)		 Synergic efficiency for erlotinib-cyclopamine association and provide a suitable in vitro model to explore drug combinations on GBM cells.
          Ellagic acid      Lagerstroemia speciosa     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 [6]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model Ba/F3 CVCL_0161 Healthy Mus musculus
WEHI-265.1 CVCL_3620 Mouse leukemia Mus musculus
                    In-vivo Model Ba/F3-insH cell line xenografts were generated by injecting 5*106 cells in 50% matrigel into six-to eight- week old male nu/nu nude mice.
                    Experimental
                    Result(s)		 The combination of ellagic acid with erlotinib has synergistic effects against EGFR H773_V774 insH mutation.
          Epigallocatechin gallate      Hamamelis virginiana     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 [7]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Phosphorylation AKT1  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP9  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation EGFR  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation ERK1  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
                    In-vitro Model Tu 177 CVCL_4913 Laryngeal squamous cell carcinoma Homo sapiens
Tu 212 CVCL_4915 Head and neck squamous cell carcinoma Homo sapiens
MDA-886Ln CVCL_6987 Laryngeal squamous cell carcinoma Homo sapiens
SqCC/Y1 CVCL_0551 Oral cavity squamous cell carcinoma Homo sapiens
                    In-vivo Model Animal models were constructed by injecting Tu212 cells (2*106) into the right flank of nude mice (athymic nu/nu).
                    Experimental
                    Result(s)		 The combined treatment resulted in significantly greater inhibition of tumor growth and delayed tumor progression as a result of increased apoptosis, decreased cell proliferation and reduced pEGFR and pAKT compared to the single agent treatment groups.
          Metformin      Galega officinalis     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 [8]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vivo Model Clinical trial
                    Experimental
                    Result(s)		 Metformin and EGFR-TKI have a synergistic effect in the treatment of DM2 NSCLC patients harboring EGFR-activating mutations.
          Shikonin      Lithospermum erythrorhizon     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 [9]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Phosphorylation AKT1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation EGFR  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation PLCG1  Molecule Info 
Pathway MAP
                    In-vitro Model U-87MG ATCC CVCL_0022 Glioblastoma Homo sapiens
DK-MG CVCL_1173 Glioblastoma Homo sapiens
SNB-19 CVCL_0535 Glioblastoma Homo sapiens
BS-153 CVCL_S444 Glioblastoma Homo sapiens
A-172 CVCL_0131 Glioblastoma Homo sapiens
T98G CVCL_0556 Glioblastoma Homo sapiens
U-251MG CVCL_0021 Astrocytoma Homo sapiens
                    Experimental
                    Result(s)		 Shikonin not only dose-dependently inhibited EGFR phosphorylation and decreased phosphorylation of EGFR downstream molecules, including AKT, P44/42MAPK and PLCgamma1, but also together with erlotinib synergistically inhibited deltaEGFR phosphorylation in U87MG.
          Triptolide      Tripterygium hypoglaucum     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 [10]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Phosphorylation AKT1  Molecule Info 
Pathway MAP
Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Up-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation EGFR  Molecule Info 
Pathway MAP
                    In-vitro Model NCI-H1975 CVCL_1511 Lung adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Combined treatment with triptolide and tyrosine kinase inhibitors synergistically enhances apoptosis in non-small cell lung cancer H1975 cells but not H1299 cells through EGFR/Akt pathway.
    β. A List of Natural Product(s) Able to Reverse the Resistance of This Drug
          Ampelopsin      Ampelopsis cordata     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 [11]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression CYBB  Molecule Info 
Pathway MAP
                    In-vitro Model NCI-H1975 CVCL_1511 Lung adenocarcinoma Homo sapiens
NCI-H1650 CVCL_1483 Lung adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 The combination of erlotinib and ampelopsin induces cell death via the Nox2-ROS-Bim pathway, and ampelopsin could be used as a novel anti-cancer agent combined with EGFR-TKI to overcome resistance to erlotinib in EGFR-mutant NSCLC.
          Celastrol      Celastrus strigillosus     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 [12]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Phosphorylation AKT1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation EGFR  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation ERK1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation STAT3  Molecule Info 
Pathway MAP
                    In-vitro Model A-549 CVCL_0023 Lung adenocarcinoma Homo sapiens
NCI-H1975 CVCL_1511 Lung adenocarcinoma Homo sapiens
                    In-vivo Model Each mouse (five-week-old BALB/c nude mice) was subcutaneously injected with 2 * 106 H1975 lung carcinoma cells in logarithmic growth phase.
                    Experimental
                    Result(s)		 Celastrol improves the therapeutic efficacy of EGFR-TKIs for non-small-cell lung cancer by overcoming EGFR T790M drug resistance.
          Silibinin      Carduus marianus     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 [13]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Phosphorylation AKT1  Molecule Info 
Pathway MAP
Down-regulation Expression EGFR  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation ERK1  Molecule Info 
Pathway MAP
                    In-vitro Model A-549 CVCL_0023 Lung adenocarcinoma Homo sapiens
NCI-H460 CVCL_0459 Lung large cell carcinoma Homo sapiens
NCI-H1299 CVCL_0060 Lung large cell carcinoma Homo sapiens
NCI-H1975 CVCL_1511 Lung adenocarcinoma Homo sapiens
HCC827 CVCL_2063 Lung adenocarcinoma Homo sapiens
LK2 CVCL_W132 Ovarian carcinoma Homo sapiens
PC-9 CVCL_B260 Lung adenocarcinoma Homo sapiens
293T GNE CVCL_0V13 Healthy Homo sapiens
                    In-vivo Model Tumors were grown by implanting 5*106 cells in Matrigel into female SCID mice flanks.
                    Experimental
                    Result(s)		 Combined treatment with silibinin and epidermal growth factor receptor tyrosine kinase inhibitors overcomes drug resistance caused by T790M mutation.
Target and Pathway
Target(s) Epidermal growth factor receptor (EGFR)  Molecule Info  [14]
KEGG Pathway MAPK signaling pathway Click to Show/Hide
2 ErbB signaling pathway
3 Ras signaling pathway
4 Rap1 signaling pathway
5 Calcium signaling pathway
6 Cytokine-cytokine receptor interaction
7 HIF-1 signaling pathway
8 FoxO signaling pathway
9 Endocytosis
10 PI3K-Akt signaling pathway
11 Dorso-ventral axis formation
12 Focal adhesion
13 Adherens junction
14 Gap junction
15 Regulation of actin cytoskeleton
16 GnRH signaling pathway
17 Estrogen signaling pathway
18 Oxytocin signaling pathway
19 Epithelial cell signaling in Helicobacter pylori infection
20 Hepatitis C
21 Pathways in cancer
22 Proteoglycans in cancer
23 MicroRNAs in cancer
24 Pancreatic cancer
25 Endometrial cancer
26 Glioma
27 Prostate cancer
28 Melanoma
29 Bladder cancer
30 Non-small cell lung cancer
31 Central carbon metabolism in cancer
32 Choline metabolism in cancer
NetPath Pathway IL4 Signaling Pathway Click to Show/Hide
2 EGFR1 Signaling Pathway
Panther Pathway Cadherin signaling pathway Click to Show/Hide
2 EGF receptor signaling pathway
Pathway Interaction Database LPA receptor mediated events Click to Show/Hide
2 Signaling events mediated by PTP1B
3 Arf6 signaling events
4 Signaling events mediated by TCPTP
5 Thromboxane A2 receptor signaling
6 SHP2 signaling
7 Regulation of Telomerase
8 EGF receptor (ErbB1) signaling pathway
9 EGFR-dependent Endothelin signaling events
10 Posttranslational regulation of adherens junction stability and dissassembly
11 Direct p53 effectors
12 ErbB1 downstream signaling
13 Urokinase-type plasminogen activator (uPA) and uPAR-mediated signaling
14 E-cadherin signaling in keratinocytes
15 ErbB receptor signaling network
16 Internalization of ErbB1
17 Stabilization and expansion of the E-cadherin adherens junction
18 a6b1 and a6b4 Integrin signaling
19 Syndecan-3-mediated signaling events
Reactome Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants Click to Show/Hide
2 SHC1 events in ERBB2 signaling
3 PLCG1 events in ERBB2 signaling
4 PIP3 activates AKT signaling
5 GRB2 events in EGFR signaling
6 GAB1 signalosome
7 SHC1 events in EGFR signaling
8 EGFR downregulation
9 GRB2 events in ERBB2 signaling
10 PI3K events in ERBB2 signaling
11 EGFR Transactivation by Gastrin
12 Constitutive Signaling by Aberrant PI3K in Cancer
13 Constitutive Signaling by EGFRvIII
14 RAF/MAP kinase cascade
WikiPathways ErbB Signaling Pathway Click to Show/Hide
2 Regulation of Actin Cytoskeleton
3 EGF/EGFR Signaling Pathway
4 MAPK Signaling Pathway
5 Focal Adhesion
6 Aryl Hydrocarbon Receptor Pathway
7 Extracellular vesicle-mediated signaling in recipient cells
8 TCA Cycle Nutrient Utilization and Invasiveness of Ovarian Cancer
9 Hair Follicle Development: Cytodifferentiation (Part 3 of 3)
10 Bladder Cancer
11 Hair Follicle Development: Induction (Part 1 of 3)
12 Signaling by ERBB4
13 Signaling by ERBB2
14 Gastrin-CREB signalling pathway via PKC and MAPK
15 PIP3 activates AKT signaling
16 Nanoparticle-mediated activation of receptor signaling
17 Aryl Hydrocarbon Receptor
18 Spinal Cord Injury
19 Integrated Pancreatic Cancer Pathway
20 Gastric cancer network 2
21 AGE/RAGE pathway
22 Signaling Pathways in Glioblastoma
23 Arylhydrocarbon receptor (AhR) signaling pathway
24 miR-targeted genes in muscle cell - TarBase
25 miR-targeted genes in lymphocytes - TarBase
26 miR-targeted genes in epithelium - TarBase
27 Integrated Breast Cancer Pathway
28 Signaling by EGFR
29 L1CAM interactions
References
Reference 1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4920).
Reference 2 Repression of PDK1- and LncRNA HOTAIR-Mediated EZH2 Gene Expression Contributes to the Enhancement of Atractylenolide 1 and Erlotinib in the Inhibition of Human Lung Cancer Cells. Cell Physiol Biochem. 2018;49(4):1615-1632.
Reference 3 Effects and mechanisms of betulinic acid on improving EGFR TKI-resistance of lung cancer cells. Environ Toxicol. 2018 Nov;33(11):1153-1159.
Reference 4 Capsaicin enhances erlotinib-induced cytotoxicity via AKT inactivation and excision repair cross-complementary 1 (ERCC1) down-regulation in human lung cancer cells. Toxicol Res (Camb). 2019 Mar 12;8(3):459-470.
Reference 5 Cyclopamine cooperates with EGFR inhibition to deplete stem-like cancer cells in glioblastoma-derived spheroid cultures. Neuro Oncol. 2012 Dec;14(12):1441-51.
Reference 6 Combination effects of ellagic acid with erlotinib in a Ba/F3 cell line expressing EGFR H773_V774 insH mutation. Thorac Cancer. 2020 Aug;11(8):2101-2111.
Reference 7 Synergistic inhibition of head and neck tumor growth by green tea (-)-epigallocatechin-3-gallate and EGFR tyrosine kinase inhibitor. Int J Cancer. 2008 Sep 1;123(5):1005-14.
Reference 8 Synergistic effects of metformin in combination with EGFR-TKI in the treatment of patients with advanced non-small cell lung cancer and type 2 diabetes. Cancer Lett. 2015 Dec 1;369(1):97-102.
Reference 9 Shikonin and its derivatives inhibit the epidermal growth factor receptor signaling and synergistically kill glioblastoma cells in combination with erlotinib. Int J Cancer. 2015 Sep 15;137(6):1446-56.
Reference 10 Combined Treatment with Triptolide and Tyrosine Kinase Inhibitors Synergistically Enhances Apoptosis in Non-small Cell Lung Cancer H1975 Cells but Not H1299 Cells through EGFR/Akt Pathway. Chem Pharm Bull (Tokyo). 2019 Aug 1;67(8):864-871.
Reference 11 Combination treatment with erlotinib and ampelopsin overcomes erlotinib resistance in NSCLC cells via the Nox2-ROS-Bim pathway. Lung Cancer. 2017 Apr;106:115-124.
Reference 12 Celastrol improves the therapeutic efficacy of EGFR-TKIs for non-small-cell lung cancer by overcoming EGFR T790M drug resistance. Anticancer Drugs. 2018 Sep;29(8):748-755.
Reference 13 Combined treatment with silibinin and epidermal growth factor receptor tyrosine kinase inhibitors overcomes drug resistance caused by T790M mutation. Mol Cancer Ther. 2010 Dec;9(12):3233-43.
Reference 14 Quantitative prediction of fold resistance for inhibitors of EGFR. Biochemistry. 2009 Sep 8;48(35):8435-48.
 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      
 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      
 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      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link