WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H205847
CAS#: 1204313-51-8 (HCl)
Description: Icotinib, also known as BPI-2009, is an orally available quinazoline-based inhibitor of epidermal growth factor receptor (EGFR), with potential antineoplastic activity. Icotinib selectively inhibits the wild-type and several mutated forms of EGFR tyrosine kinase. This may lead to an inhibition of EGFR-mediated signal transduction and may inhibit cancer cell proliferation. EGFR, a receptor tyrosine kinase, is upregulated in a variety of cancer cell types.
Hodoodo Cat#: H205847
Name: Icotinib HCl
CAS#: 1204313-51-8 (HCl)
Chemical Formula: C22H22ClN3O4
Exact Mass: 0.00
Molecular Weight: 427.890
Elemental Analysis: C, 61.76; H, 5.18; Cl, 8.28; N, 9.82; O, 14.96
Related CAS #: 1204313-51-8 (HCl) 610798-31-7 (free base)
Synonym: BPI2009; BPI 2009; BPI-2009; Icotinib; Brand name: Conmana.
IUPAC/Chemical Name: N-(3-ethynylphenyl)-7,8,10,11,13,14-hexahydro-[1,4,7,10]tetraoxacyclododecino[2,3-g]quinazolin-4-amine hydrochloride
InChi Key: PNNGXMJMUUJHAV-UHFFFAOYSA-N
InChi Code: InChI=1S/C22H21N3O4.ClH/c1-2-16-4-3-5-17(12-16)25-22-18-13-20-21(14-19(18)23-15-24-22)29-11-9-27-7-6-26-8-10-28-20;/h1,3-5,12-15H,6-11H2,(H,23,24,25);1H
SMILES Code: C#CC1=CC(NC2=C3C=C(OCCOCCOCCO4)C4=CC3=NC=N2)=CC=C1.[H]Cl
Appearance: Light yellow solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info: Icotinib was approved in China in 2011.
| Biological target: | Icotinib Hydrochloride (BPI-2009) is an EGFR inhibitor with an IC50 of 5 nM. |
| In vitro activity: | Ten HCC (hepatocellular carcinoma) cell lines were selected to test their original EGFR-activation status and PDL1 protein level, and in vitro antiproliferation assays were also conducted to analyze the IC50 and further investigate the correlation between IC50 and protein level of phosphorylated EGFR and PDL1. Icotinib showed significant inhibitory effects only on HCC cell lines that had both higher p-EGFR and PDL1 protein level. Molecular mechanism study revealed that icotinib inhibited the phosphorylation of EGFR and PDL1 expression in cancer cells and activated apoptosis. Knocking down PDL1 significantly reduced the inhibitory effect of icotinib on HCC, and knocking in PDL1 increased the sensitivity of icotinib in HCC. These results suggest that icotinib has an inhibitory effect on a subgroup of HCC cells that have both higher p-EGFR and PDL1. Reference: Onco Targets Ther. 2018 Nov 21;11:8227-8237. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6254541/ |
| In vivo activity: | Huh7 cells were injected subcutaneously into the right limb, and when tumors had reached 100 mm3, the mice began to receive icotinib administration every 2 days. The whole treatment lasted 3 weeks. Tumor sizes in the control group increased significantly. Compared with the control group, tumor volumes in the icotinib treated group decreased dose-dependently, and the difference was statistically significant (Figure 6), which suggested that icotinib reduced sensitive HCC-tumor growth in vivo. Reference: Onco Targets Ther. 2018 Nov 21;11:8227-8237. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6254541/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 51.5 | 120.36 | |
| Ethanol | 7.0 | 16.36 |
The following data is based on the product molecular weight 427.89 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Sun J, Jiang W, Tian D, Guo Q, Shen Z. Icotinib inhibits the proliferation of hepatocellular carcinoma cells in vitro and in vivo dependently on EGFR activation and PDL1 expression. Onco Targets Ther. 2018 Nov 21;11:8227-8237. doi: 10.2147/OTT.S179844. PMID: 30538492; PMCID: PMC6254541. 2. Zhang S, Fu Y, Wang D, Wang J. Icotinib enhances lung cancer cell radiosensitivity in vitro and in vivo by inhibiting MAPK/ERK and AKT activation. Clin Exp Pharmacol Physiol. 2018 May 16. doi: 10.1111/1440-1681.12966. Epub ahead of print. PMID: 29770473. |
| In vitro protocol: | 1. Sun J, Jiang W, Tian D, Guo Q, Shen Z. Icotinib inhibits the proliferation of hepatocellular carcinoma cells in vitro and in vivo dependently on EGFR activation and PDL1 expression. Onco Targets Ther. 2018 Nov 21;11:8227-8237. doi: 10.2147/OTT.S179844. PMID: 30538492; PMCID: PMC6254541. 2. Zhang S, Fu Y, Wang D, Wang J. Icotinib enhances lung cancer cell radiosensitivity in vitro and in vivo by inhibiting MAPK/ERK and AKT activation. Clin Exp Pharmacol Physiol. 2018 May 16. doi: 10.1111/1440-1681.12966. Epub ahead of print. PMID: 29770473. |
| In vivo protocol: | 1. Sun J, Jiang W, Tian D, Guo Q, Shen Z. Icotinib inhibits the proliferation of hepatocellular carcinoma cells in vitro and in vivo dependently on EGFR activation and PDL1 expression. Onco Targets Ther. 2018 Nov 21;11:8227-8237. doi: 10.2147/OTT.S179844. PMID: 30538492; PMCID: PMC6254541. 2. Zhang S, Fu Y, Wang D, Wang J. Icotinib enhances lung cancer cell radiosensitivity in vitro and in vivo by inhibiting MAPK/ERK and AKT activation. Clin Exp Pharmacol Physiol. 2018 May 16. doi: 10.1111/1440-1681.12966. Epub ahead of print. PMID: 29770473. |
1: Chen X, Zhu Q, Liu Y, Liu P, Yin Y, Guo R, Lu K, Gu Y, Liu L, Wang J, Wang Z, Røe OD, Shu Y, Zhu L. Icotinib is an active treatment of non-small-cell lung cancer: a retrospective study. PLoS One. 2014 May 16;9(5):e95897. doi: 10.1371/journal.pone.0095897. eCollection 2014. PubMed PMID: 24836053; PubMed Central PMCID: PMC4023939.
2: Pan H, Liu R, Li S, Fang H, Wang Z, Huang S, Zhou J. Effects of Icotinib on Advanced Non-Small Cell Lung Cancer with Different EGFR Phenotypes. Cell Biochem Biophys. 2014 Apr 29. [Epub ahead of print] PubMed PMID: 24777808.
3: Guan YS, He Q, Li M. Icotinib: activity and clinical application in Chinese patients with lung cancer. Expert Opin Pharmacother. 2014 Apr;15(5):717-28. doi: 10.1517/14656566.2014.890183. Epub 2014 Mar 4. PubMed PMID: 24588695.
4: Liang W, Wu X, Fang W, Zhao Y, Yang Y, Hu Z, Xue C, Zhang J, Zhang J, Ma Y, Zhou T, Yan Y, Hou X, Qin T, Dinglin X, Tian Y, Huang P, Huang Y, Zhao H, Zhang L. Network meta-analysis of erlotinib, gefitinib, afatinib and icotinib in patients with advanced non-small-cell lung cancer harboring EGFR mutations. PLoS One. 2014 Feb 12;9(2):e85245. doi: 10.1371/journal.pone.0085245. eCollection 2014. PubMed PMID: 24533047; PubMed Central PMCID: PMC3922700.
5: Liu D, Jiang J, Zhang L, Tan F, Wang Y, Zhang D, Hu P. Clinical pharmacokinetics of Icotinib, an anti-cancer drug: evaluation of dose proportionality, food effect, and tolerability in healthy subjects. Cancer Chemother Pharmacol. 2014 Apr;73(4):721-7. doi: 10.1007/s00280-014-2398-8. Epub 2014 Feb 1. PubMed PMID: 24488324.
6: Shao L, Zhang B, He C, Lin B, Song Z, Lou G, Yu X, Zhang Y. Efficacy and safety of icotinib in Chinese patients with advanced non-small cell lung cancer after failure of chemotherapy. Chin Med J (Engl). 2014;127(2):266-71. PubMed PMID: 24438614.
7: Guan Y, Zhao H, Meng J, Yan X, Jiao S. Dramatic response to high-dose icotinib in a lung adenocarcinoma patient after erlotinib failure. Lung Cancer. 2014 Feb;83(2):305-7. doi: 10.1016/j.lungcan.2013.12.002. Epub 2013 Dec 12. PubMed PMID: 24370197.
8: Zhao Q, Wang Y, Tang Y, Peng L. Icotinib combined with rapamycin in a renal transplant recipient with epidermal growth factor receptor-mutated non-small cell lung cancer: A case report. Oncol Lett. 2014 Jan;7(1):171-176. Epub 2013 Nov 5. PubMed PMID: 24348843; PubMed Central PMCID: PMC3861587.
9: Sun X, Zheng Y. Retreatment with icotinib in a patient with metastatic lung adenocarcinoma. Tumori. 2013 May-Jun;99(3):e124-6. doi: 10.1700/1334.14820. PubMed PMID: 24158081.
10: Shi Y, Zhang L, Liu X, Zhou C, Zhang L, Zhang S, Wang D, Li Q, Qin S, Hu C, Zhang Y, Chen J, Cheng Y, Feng J, Zhang H, Song Y, Wu YL, Xu N, Zhou J, Luo R, Bai C, Jin Y, Liu W, Wei Z, Tan F, Wang Y, Ding L, Dai H, Jiao S, Wang J, Liang L, Zhang W, Sun Y. Icotinib versus gefitinib in previously treated advanced non-small-cell lung cancer (ICOGEN): a randomised, double-blind phase 3 non-inferiority trial. Lancet Oncol. 2013 Sep;14(10):953-61. doi: 10.1016/S1470-2045(13)70355-3. Epub 2013 Aug 13. PubMed PMID: 23948351.
11: Camidge DR. Icotinib: kick-starting the Chinese anticancer drug industry. Lancet Oncol. 2013 Sep;14(10):913-4. doi: 10.1016/S1470-2045(13)70385-1. Epub 2013 Aug 13. PubMed PMID: 23948350.
12: Yang X, Zhang H, Qin N, Li X, Nong J, Lv J, Wu Y, Zhang Q, Zhang S. [Clinical observation of icotinib hydrochloride in first-line therapy for pulmonary adenocarcinoma]. Zhongguo Fei Ai Za Zhi. 2013 Jul;16(7):364-8. doi: 10.3779/j.issn.1009-3419.2013.07.06. Chinese. PubMed PMID: 23866667.
13: Nong J, Qin N, Wang J, Yang X, Zhang H, Wu Y, Lv J, Zhang Q, Zhang S. [Clinical effects for patients with recurrent advanced non-small cell lung cancer treated with icotinib hydrochloride]. Zhongguo Fei Ai Za Zhi. 2013 May;16(5):240-5. doi: 10.3779/j.issn.1009-3419.2013.05.05. Chinese. PubMed PMID: 23676980.
14: Lv C, Ma Y, Feng Q, Fang F, Bai H, Zhao B, Yan S, Wu N, Zheng Q, Li S, Chen J, Wang J, Feng Y, Wang Y, Pei Y, Fang J, Yang Y. A pilot study: sequential gemcitabine/cisplatin and icotinib as induction therapy for stage IIB to IIIA non-small-cell lung adenocarcinoma. World J Surg Oncol. 2013 Apr 26;11:96. doi: 10.1186/1477-7819-11-96. PubMed PMID: 23621919; PubMed Central PMCID: PMC3643858.
15: Gao Z, Chen W, Zhang X, Cai P, Fang X, Xu Q, Sun Y, Gu Y. Icotinib, a potent and specific EGFR tyrosine kinase inhibitor, inhibits growth of squamous cell carcinoma cell line A431 through negatively regulating AKT signaling. Biomed Pharmacother. 2013 Jun;67(5):351-6. doi: 10.1016/j.biopha.2013.03.012. Epub 2013 Apr 2. PubMed PMID: 23602321.
16: Mu X, Zhang Y, Qu X, Hou K, Kang J, Hu X, Liu Y. Ubiquitin ligase Cbl-b is involved in icotinib (BPI-2009H)-induced apoptosis and G1 phase arrest of EGFR mutation-positive non-small-cell lung cancer. Biomed Res Int. 2013;2013:726375. doi: 10.1155/2013/726375. Epub 2013 Mar 19. PubMed PMID: 23586056; PubMed Central PMCID: PMC3615596.
17: Song Z, Yu X, Cai J, Shao L, Lin B, He C, Zhang B, Zhang Y. [Efficacy of icotinib for advanced non-small cell lung cancer patients with EGFR status identified]. Zhongguo Fei Ai Za Zhi. 2013 Mar;16(3):138-43. doi: 10.3779/j.issn.1009-3419.2013.03.04. Chinese. PubMed PMID: 23514942.
18: Gu A, Shi C, Xiong L, Chu T, Pei J, Han B. Efficacy and safety evaluation of icotinib in patients with advanced non-small cell lung cancer. Chin J Cancer Res. 2013 Feb;25(1):90-4. doi: 10.3978/j.issn.1000-9604.2012.12.07. PubMed PMID: 23372346; PubMed Central PMCID: PMC3555305.
19: Zhao Q, Wang YN, Wang B. Spared pre-irradiated area in pustular lesions induced by icotinib showing decreased expressions of CD1a+ langerhans cells and FGFR2. Jpn J Clin Oncol. 2013 Feb;43(2):200-4. doi: 10.1093/jjco/hys209. Epub 2012 Dec 21. PubMed PMID: 23264674.
20: Zheng Y, Fang W, Xu N. Hand-foot syndrome in a patient with metastatic lung adenocarcinoma induced by high-dose icotinib: A case report and review of the literature. Oncol Lett. 2012 Dec;4(6):1341-1343. Epub 2012 Sep 10. PubMed PMID: 23205134; PubMed Central PMCID: PMC3506748.
