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- Gefitinib (ZD1839)
Gefitinib (ZD1839)
Gefitinib, also known as ZD1839 or Iressa, is a potent and orally-bioavailable small-molecule inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase with 50% inhibition concentration IC50 values of 0.033 μM and 0.027 μM in A431 membrane prep and baculovirus lysate respectively. Gefitinib binds to the kinase ATP binding site of EGFR interfering with the binding of adenosine triphosphate, which suppresses the EGFR tyrosine kinase activity and resultant signal transduction of EGFR. Gefitinib exhibits anti-angiogenic activities in a wide range of human tumor types, including head and neck, prostate, breast, ovarian, colon, small-cell lung and non-small-cell lung cancer. Moreover, geftinib has also been found to reduce proliferation, induce cell cycle arrest and increase apoptosis.
Reference
M. Ranson and S. Wardell. Gefitinib, a novel, orally administered agent for the treatment of cancer. Journal of Clinical Pharmacy and Therapeutics (2004) 29, 95-103
Joachim Von Pawel. Gefitinib (Iressa, ZD1839): a novel targeted approach for the treatment of solid tumors. Bull Cancer 2004; 91(5): E70-E76
- 1. Jing Ma, Chao Dong, et al. "Dual Target of EGFR and mTOR Suppress Triple Negative Breast Cancer Cell Growth Via Regulation The Phosphorylation of mTOR Downstream Proteins." Breast Cancer (Dove Med Press). 2023 Jan 17;15:11-24. PMID: 36691572
- 2. Corina M Stewart, Alexandra Phan, et al. "Ebola virus triggers receptor tyrosine kinase-dependent signaling to promote the delivery of viral particles to entry-conducive intracellular compartments." PLoS Pathog. 2021 Jan 29;17(1):e1009275. PMID: 33513206
- 3. Priscilla Cheung, Jordi Xiol, et al. "Regenerative Reprogramming of the Intestinal Stem Cell State via Hippo Signaling Suppresses Metastatic Colorectal Cancer." Cell Stem Cell. 2020 Oct 1;27(4):590-604.e9. PMID: 32730753
- 4. Lina Zhao, Ting Qiu, et al. "SGCE Promotes Breast Cancer Stem Cells by Stabilizing EGFR." Adv Sci (Weinh). 2020 Jun 8;7(14):1903700. PMID: 32714745
- 5. Lee YC, Wang LJ, et al. "Inhibition of EGFR pathway promotes the cytotoxicity of ABT-263 in human leukemia K562 cells by blocking MCL1 upregulation." Biochem Pharmacol. 2020;178:114047. PMID: 32446890
- 6. White SM, Avantaggiati ML, et al. "YAP/TAZ Inhibition Induces Metabolic and Signaling Rewiring Resulting in Targetable Vulnerabilities in NF2-Deficient Tumor Cells." Dev Cell. 2019 May 6;49(3):425-443.e9. PMID: 31063758
- 7. She K, Fang S, et al. "SCD1 is required for EGFR-targeting cancer therapy of lung cancer via re-activation of EGFR/PI3K/AKT signals." Cancer Cell Int. 2019 Apr 18;19:103. PMID: 31019378
- 8. Chen Z, Tian D, et al. "Apigenin Combined With Gefitinib Blocks Autophagy Flux and Induces Apoptotic Cell Death Through Inhibition of HIF-1α, c-Myc, p-EGFR, and Glucose Metabolism in EGFR L858R+T790M-Mutated H1975 Cells." Front Pharmacol. 2019 Mar 22;10:260. PMID: 30967777
- 9. Huang SZ, Wei MN, et al. "Targeting TF-AKT/ERK-EGFR Pathway Suppresses the Growth of Hepatocellular Carcinoma." Front Oncol. 2019 Mar 15;9:150. PMID: 30931258
- 10. Hu WT, Yeh CC, et al. "The O-glycosylating enzyme GALNT2 suppresses the malignancy of gastric adenocarcinoma by reducing EGFR activities." Am J Cancer Res. 2018 Sep 1;8(9):1739-1751. PMID: 30323967
- 11. Cheriyan VT, Alsaab H, et al. "A CARP-1 functional mimetic compound is synergistic with BRAF-targeting in non-small cell lung cancers." Oncotarget. 2018 Jul 3;9(51):29680-29697. PMID: 30038713
- 12. Shih CH, Chang YJ, et al. "EZH2-mediated upregulation of ROS1 oncogene promotes oral cancer metastasis." Oncogene. 2017 Nov 23;36(47):6542-6554. PMID: 28759046
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 446.90 |
| Cas No. | 184475-35-2 |
| Formula | C22H24ClFN4O3 |
| Synonyms | Iressa, ZD-1839, Gefitinib |
| Solubility | ≥22.34 mg/mL in DMSO; insoluble in H2O; ≥2.48 mg/mL in EtOH with ultrasonic |
| Chemical Name | N-(3-chloro-4-fluorophenyl)-7-methoxy-6-(3-morpholin-4-ylpropoxy)quinazolin-4-amine |
| SDF | Download SDF |
| Canonical SMILES | COC1=C(C=C2C(=C1)N=CN=C2NC3=CC(=C(C=C3)F)Cl)OCCCN4CCOCC4 |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment: [1] | |
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Cell lines |
BT-474 cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
1 μM, 24 hours |
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Applications |
A 24-h treatment of BT-474 cells with 1 μM ZD1839 increased the G1 fraction from 74 to 88% and reduced the proportion of cells in S from 15 to 4%. Simultaneous with the accumulation of cells in G1 was complete elimination of both active Akt and MAPK, as measured with phosphospecific antibodies, without changes in the content of total Akt and MAPK. Consistent with the inhibition of Akt activity, phosphorylation of GSK-3β, a target of the Akt kinase, was reduced. Cyclin D1 and Cdk4 were also reduced, whereas protein levels of the Cdk inhibitor p27 were up-regulated. |
| Animal experiment: [1] | |
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Animal models |
Female Balb/C athymic nude mice injected with BT-474 cells |
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Dosage form |
Oral administration, 200 mg/kg/day |
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Applications |
Mice were randomly allocated to either no treatment, ZD1839, Herceptin, or the combination. ZD1839 completely prevented tumor growth but did not induce complete remissions. Herceptin alone induced complete remission in two of seven, whereas the combination resulted in three of eight complete responses. No mice exhibited treatment-related toxicity. Three mice treated with ZD1839 plus Herceptin, in which tumors regressed completely, remained tumor free for >6 months after discontinuation of therapy and had no detectable tumor at necropsy. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Moulder S L, Yakes F M, Muthuswamy S K, et al. Epidermal growth factor receptor (HER1) tyrosine kinase inhibitor ZD1839 (Iressa) inhibits HER2/neu (erbB2)-overexpressing breast cancer cells in vitro and in vivo. Cancer research, 2001, 61 (24): 8887-8895. |
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| Description | Gefitinib (ZD-1839) is an inhibitor of EGFR for Tyr1173, Tyr992, Tyr1173 and Tyr992 in the NR6wtEGFR and NR6W cells with IC50 of 37 nM, 37 nM, 26 nM and 57 nM, respectively. | |||||
| Targets | Tyr1173 (NR6wtEGFR cells) | Tyr992 (NR6wtEGFR cells) | Tyr1173 (NR6W cells) | Tyr992 (NR6W cells) | ||
| IC50 | 37 nM | 37nM | 26 nM | 57 nM | ||
Quality Control & MSDS
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