Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C16H14BrN3O2.ClH |
| Molecular Weight | 396.666 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.COC1=CC2=NC=NC(NC3=CC=CC(Br)=C3)=C2C=C1OC
InChI
InChIKey=ZJOKWAWPAPMNIM-UHFFFAOYSA-N
InChI=1S/C16H14BrN3O2.ClH/c1-21-14-7-12-13(8-15(14)22-2)18-9-19-16(12)20-11-5-3-4-10(17)6-11;/h3-9H,1-2H3,(H,18,19,20);1H
| Molecular Formula | ClH |
| Molecular Weight | 36.461 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
| Molecular Formula | C16H14BrN3O2 |
| Molecular Weight | 360.205 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
DescriptionCurator's Comment: The description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/8824347 | https://www.ncbi.nlm.nih.gov/pubmed/24335566 | https://www.ncbi.nlm.nih.gov/pubmed/16279804
Curator's Comment: The description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/8824347 | https://www.ncbi.nlm.nih.gov/pubmed/24335566 | https://www.ncbi.nlm.nih.gov/pubmed/16279804
PD-153035 is a potent and selective ATP-competitive inhibitor of the epidermal growth factor receptor tyrosine kinase EGFR. PD 153035 shows a potent and selective inhibitory effect on tyrosine phosphorylation induced by EGF in Swiss 3T3 fibroblast and A-431 human epidermoid carcinoma cells. PD153035 shows dose-dependent growth inhibitory effects in cultures of EGF receptor-overexpressing human cancer cell lines (A431, Difi, DU145, MDA-MB-468, and ME180) and in nasopharyngeal carcinoma (NPC) cell lines (NPC-TW01, NPC-TW04, and HONE1). Pretreatment of EGFR inhibitors by 24 hours significantly enhances the cytotoxic effect of doxorubicin, paclitaxel, cisplatin, and 5-fluorouracil in NPCTW04 cells. PD153035 abolishes COX-2 expression induced by the PAR(2)-activating peptide 2-furoyl-LIGRLO-NH(2) (2fLI) in Caco-2 colon cancer cells. In A431 human epidermoid tumors grown as xenografts in immunodeficient nude mice, PD153035 at 80 mg/kg i.p. inhibit EGF receptor tyrosine kinase activity. PD153035 improves glucose tolerance, insulin sensitivity, and signaling and reduces subclinical inflammation in HFD-fed mice.
CNS Activity
Originator
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL2034 |
2.6 nM [IC50] | ||
Target ID: CHEMBL3009 |
49.0 nM [IC50] | ||
Target ID: CHEMBL2111431 |
70.0 nM [IC50] | ||
Target ID: CHEMBL1862 |
30.0 nM [IC50] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Diagnostic | Unknown Approved UseUnknown |
|||
| Primary | Unknown Approved UseUnknown |
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| inconclusive [EC50 5.0119 uM] | ||||
| inconclusive [IC50 10 uM] | ||||
| yes [IC50 0.3981 uM] | ||||
| yes [IC50 0.5012 uM] | ||||
| yes [IC50 1.62 uM] | ||||
| yes [IC50 1.9953 uM] | ||||
| yes [IC50 29.5 uM] | ||||
| yes [IC50 5.0119 uM] |
Drug as victim
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| yes | ||||
| yes |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Antitumor activity of a novel EGFR tyrosine kinase inhibitor against human lung carcinoma in vitro and in vivo. | 2009-02 |
|
| Curcumin attenuates EGF-induced AQP3 up-regulation and cell migration in human ovarian cancer cells. | 2008-10 |
|
| Priming with EGFR tyrosine kinase inhibitor and EGF sensitizes ovarian cancer cells to respond to chemotherapeutical drugs. | 2008-08-08 |
|
| HTS assays using a disease-relevant cell model for interrogating the MAP kinase pathway initiated by multiple receptors. | 2008-06 |
|
| [Molecular imaging of epidermal growth factor receptor in glioma-bearing rats]. | 2008-05 |
|
| Leptin stimulates the proliferation of human oesophageal adenocarcinoma cells via HB-EGF and Tgfalpha mediated transactivation of the epidermal growth factor receptor. | 2008 |
|
| Biochemical assay-based selectivity profiling of clinically relevant kinase inhibitors on mutant forms of EGF receptor. | 2008 |
|
| Activation of epidermal growth factor receptor by metal-ligand complexes decreases levels of extracellular amyloid beta peptide. | 2008 |
|
| The DNA-binding epidermal growth factor-receptor inhibitor PD153035 and other DNA-intercalating cytotoxic drugs reactivate the expression of the retinoic acid receptor-beta tumor-suppressor gene in breast cancer cells. | 2007-11 |
|
| Assessment of 11C-labeled-4-N-(3-bromoanilino)-6,7-dimethoxyquinazoline as a positron emission tomography agent to monitor epidermal growth factor receptor expression. | 2007-09 |
|
| Signaling pathway for 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced TNF-alpha production in differentiated THP-1 human macrophages. | 2007-08-31 |
|
| Further characterization of the epidermal growth factor receptor ligand 11C-PD153035. | 2007-06-05 |
|
| Upregulation of retinoic acid receptor-beta by the epidermal growth factor-receptor inhibitor PD153035 is not mediated by blockade of ErbB pathways. | 2007-06 |
|
| Protein C is an autocrine growth factor for human skin keratinocytes. | 2007-05-04 |
|
| [Expressions of epidermal growth factor receptor signaling substances in gastric mucosal cells influenced by serum derived from rats treated with electroacupuncture at stomach meridian acupoints]. | 2007-05 |
|
| Blockage of epidermal growth factor receptor by quinazoline tyrosine kinase inhibitors suppresses growth of human hepatocellular carcinoma. | 2007-04-08 |
|
| Immortalization of human urothelial cells by human papillomavirus type 16 E6 and E7 genes in a defined serum-free system. | 2007-04 |
|
| EGF receptor clustering is induced by a 0.4 mT power frequency magnetic field and blocked by the EGF receptor tyrosine kinase inhibitor PD153035. | 2007-04 |
|
| Control of PDGF-induced reactive oxygen species (ROS) generation and signal transduction in human lens epithelial cells. | 2007-03-14 |
|
| Control of tight junctional sealing: role of epidermal growth factor. | 2007-02 |
|
| Epidermal growth factor receptor inhibition sensitizes renal cell carcinoma cells to the cytotoxic effects of bortezomib. | 2007-01 |
|
| QSAR analysis of tyrosine kinase inhibitor using modified ant colony optimization and multiple linear regression. | 2007-01 |
|
| EGFR-mediated expression of aquaporin-3 is involved in human skin fibroblast migration. | 2006-12-01 |
|
| The tyrosine kinase inhibitor PD153035: implication of labeling position on radiometabolites formed in vitro. | 2006-11 |
|
| UVB radiation induces expression of HIF-1alpha and VEGF through the EGFR/PI3K/DEC1 pathway. | 2006-10 |
|
| Asbestos-induced activation of cell signaling pathways in human bronchial epithelial cells. | 2006-08-16 |
|
| PPARgamma-regulated tight junction development during human urothelial cytodifferentiation. | 2006-08 |
|
| Inhibition of protein tyrosine phosphatase activity mediates epidermal growth factor receptor signaling in human airway epithelial cells exposed to Zn2+. | 2006-07-01 |
|
| Inhibition of EGFR/PI3K/AKT cell survival pathway promotes TSA's effect on cell death and migration in human ovarian cancer cells. | 2006-07 |
|
| Amphiregulin contributes to the transformed phenotype of human hepatocellular carcinoma cells. | 2006-06-15 |
|
| The epidermal growth factor receptor (EGFR)-S442F mutant displays increased affinity for neuregulin-2beta and agonist-independent coupling with downstream signalling events. | 2006-05-15 |
|
| Indole-3-carbinol-induced death in cancer cells involves EGFR downregulation and is exacerbated in a 3D environment. | 2006-05 |
|
| COX-2-mediated stimulation of the lymphangiogenic factor VEGF-C in human breast cancer. | 2006-04-24 |
|
| Suppression of pro-metastasis phenotypes expression in malignant pleural mesothelioma by the PI3K inhibitor LY294002 or the MEK inhibitor UO126. | 2006-04-20 |
|
| Transforming growth factor alpha attenuates the functional expression of AMPA receptors in cortical GABAergic neurons. | 2006-04 |
|
| Opposite effect of ERK1/2 and JNK on p53-independent p21WAF1/CIP1 activation involved in the arsenic trioxide-induced human epidermoid carcinoma A431 cellular cytotoxicity. | 2006-01 |
|
| Epidermal growth factor-, transforming growth factor-beta-, retinoic acid- and 1,25-dihydroxyvitamin D3-regulated expression of the novel protein PTPIP51 in keratinocytes. | 2006 |
|
| Anilinodialkoxyquinazolines: screening epidermal growth factor receptor tyrosine kinase inhibitors for potential tumor imaging probes. | 2005-11-17 |
|
| Targeted inhibition of transient activation of the EGFR-mediated cell survival pathway enhances paclitaxel-induced ovarian cancer cell death. | 2005-11 |
|
| p38 and EGF receptor kinase-mediated activation of the phosphatidylinositol 3-kinase/Akt pathway is required for Zn2+-induced cyclooxygenase-2 expression. | 2005-11 |
|
| Mechanism of thymus- and activation-regulated chemokine (TARC)/CCL17 production and its modulation by roxithromycin. | 2005-09 |
|
| Transient activation of EGFR/AKT cell survival pathway and expression of survivin contribute to reduced sensitivity of human melanoma cells to betulinic acid. | 2005-09 |
|
| Heparin-binding epidermal growth factor-like growth factor stimulates cell proliferation in cerebral cortical cultures through phosphatidylinositol 3'-kinase and mitogen-activated protein kinase. | 2005-08-15 |
|
| Up-regulation in endothelin-1 by Helicobacter pylori lipopolysaccharide interferes with gastric mucin synthesis via epidermal growth factor receptor transactivation. | 2005-08 |
|
| Autocrine regulation of human urothelial cell proliferation and migration during regenerative responses in vitro. | 2005-05-15 |
|
| Positive and negative transcriptional regulation of aromatase expression in human breast cancer tissue. | 2005-05 |
|
| The selective epidermal growth factor receptor tyrosine kinase inhibitor PD153035 suppresses expression of prometastasis phenotypes in malignant pleural mesothelioma cells in vitro. | 2005-05 |
|
| Inhibition of the epidermal growth factor receptor increases expression of genes that stimulate inflammation, apoptosis, and cell attachment. | 2005-04 |
|
| Comparison of ELISA-based tyrosine kinase assays for screening EGFR inhibitors. | 2005 |
|
| Porphyromonas gingivalis lipopolysaccharide-induced up-regulation in endothelin-1 interferes with salivary mucin synthesis via epidermal growth factor receptor transactivation. | 2004-10 |
Patents
Sample Use Guides
Nude mice were treated i.p. with PD-153035 as a single dose 80 mg/kg
Route of Administration:
Intraperitoneal
A43l, MDA-MB-231, MDA-MB-453, MDA-MB-468, SK-BR-3, DU145, and Difi cells were used for activity evaluation. Cells were seeded in six well plates (model 3046; Falcon, Lincoln Park, NJ) at l0^4 cells/well. The next day, cells were changed to medium containing 0.5% FBS for 18 h, and then PD153035 (0.125, 0.25, 0.5 and 2.5 mkM) was added to the cultures. After 72 h of treatment, cells were washed once with PBS, harvested with 0.1% human trypsin-l mM EDTA in PBS, and counted with a Coulter counter.
| Substance Class |
Chemical
Created
by
admin
on
Edited
Mon Mar 31 18:06:44 GMT 2025
by
admin
on
Mon Mar 31 18:06:44 GMT 2025
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| Record UNII |
AHJ252P69N
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| Record Status |
Validated (UNII)
|
| Record Version |
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AHJ252P69N
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