WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H330109
CAS#: 248594-19-6 (mesylate)
Description: Erlotinib is an epidermal growth factor receptor inhibitor (EGFR inhibitor). Erlotinib HCl was approved. Erlotinib binds in a reversible fashion to the adenosine triphosphate (ATP) binding site of the receptor. For the signal to be transmitted, two EGFR molecules need to come together to form a homodimer. These then use the molecule of ATP to trans-phosphorylate each other on tyrosine residues, which generates phosphotyrosine residues, recruiting the phosphotyrosine-binding proteins to EGFR to assemble protein complexes that transduce signal cascades to the nucleus or activate other cellular biochemical processes. When erlotinib binds to EGFR, formation of phosphotyrosine residues in EGFR is not possible and the signal cascades are not initiated.
Hodoodo Cat#: H330109
Name: Erlotinib mesylate
CAS#: 248594-19-6 (mesylate)
Chemical Formula: C23H27N3O7S
Exact Mass: 0.00
Molecular Weight: 489.543
Elemental Analysis: C, 56.43; H, 5.56; N, 8.58; O, 22.88; S, 6.55
Related CAS #: 183319-69-9 (HCl) 183321-74-6 (free base) 248594-19-6 (mesylate)
Synonym: Erlotinib mesylate; CP-358,774; CP-358774; CP358774; OSI-774; OSI 774; OSI774.
IUPAC/Chemical Name: N-(3-Ethynylphenyl)-6,7-bis(2-methoxyethoxy)-4-quinazolinamine methansulfonic acid
InChi Key: PCBNMUVSOAYYIH-UHFFFAOYSA-N
InChi Code: InChI=1S/C22H23N3O4.CH4O3S/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;1-5(2,3)4/h1,5-7,12-15H,8-11H2,2-3H3,(H,23,24,25);1H3,(H,2,3,4)
SMILES Code: COCCOC1=CC2=NC=NC(NC3=CC=CC(C#C)=C3)=C2C=C1OCCOC.CS(=O)(O)=O
Appearance: 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
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:
| Biological target: | Erlotinib mesylate (OSI-744, CP358774, NSC 718781) is an EGFR inhibitor with IC50 of 2 nM in cell-free assays, >1000-fold more sensitive for EGFR than human c-Src or v-Abl. |
| In vitro activity: | The first indication of affinity of erlotinib for P-gp and BCRP was obtained in in vitro studies employing cells overexpressing BCRP and P-gp. A small but statistically significant difference in IC50 was found between BCRP/Bcrp1- or P-gp-overexpressing and WT cell lines, which is apparently in contrast with the high rates of transport of erlotinib observed in Transwell experiments in Bcrp1- or P-gp-overexpressing cells. A visual inspection of the plates obtained in the colony-forming assays reveals a significant difference in growth characteristics of the colonies between cell lines and at applied different concentrations of the drug. At the same erlotinib concentration, the colonies were bigger in size in the MDR1- and BCRP-expressing cells compared with WT cells, and in the same cell line, colonies were smaller (but still composed of at least 50 cells) at higher erlotinib concentrations. Therefore, the difference in the IC50 value only may not be fully representative for the effect of MDR1 or BCRP overexpression on the cytotoxicity of erlotinib. Reference: Mol Cancer Ther. 2008 Aug;7(8):2280-7. http://mct.aacrjournals.org/cgi/pmidlookup?view=long&pmid=18723475 |
| In vivo activity: | To quantitate the effect of the absence of P-gp and Bcrp1 on the in vivo pharmacokinetics of erlotinib hydrochloride, the pharmacokinetics after p.o. and i.p. administration of the drug in WT and in Bcrp1/Mdr1a/b−/− mice was investigated. Results obtained after oral administration revealed that there is a statistically significantly increased AUC of erlotinib in triple-knockout compared with WT-mice (P = 0.01). In addition, the bioavailability of oral erlotinib was significantly increased in Bcrp1/Mdr1a/b−/− mice, considering also the small and nonsignificant difference in the systemic clearance of erlotinib found between Bcrp1/Mdr1a/b−/− and WT mice. Therefore, effective inhibition of P-gp/BCRP in patients may significantly increase the systemic exposure to erlotinib, assuming that these results obtained in mice are representative for the clinical situation. Reference: Mol Cancer Ther. 2008 Aug;7(8):2280-7. http://mct.aacrjournals.org/cgi/pmidlookup?view=long&pmid=18723475 |
The following data is based on the product molecular weight 489.54 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. Marchetti S, de Vries NA, Buckle T, Bolijn MJ, van Eijndhoven MA, Beijnen JH, Mazzanti R, van Tellingen O, Schellens JH. Effect of the ATP-binding cassette drug transporters ABCB1, ABCG2, and ABCC2 on erlotinib hydrochloride (Tarceva) disposition in in vitro and in vivo pharmacokinetic studies employing Bcrp1-/-/Mdr1a/1b-/- (triple-knockout) and wild-type mice. Mol Cancer Ther. 2008 Aug;7(8):2280-7. doi: 10.1158/1535-7163.MCT-07-2250. PMID: 18723475. 2. Moyer JD, Barbacci EG, Iwata KK, Arnold L, Boman B, Cunningham A, DiOrio C, Doty J, Morin MJ, Moyer MP, Neveu M, Pollack VA, Pustilnik LR, Reynolds MM, Sloan D, Theleman A, Miller P. Induction of apoptosis and cell cycle arrest by CP-358,774, an inhibitor of epidermal growth factor receptor tyrosine kinase. Cancer Res. 1997 Nov 1;57(21):4838-48. PMID: 9354447. |
| In vitro protocol: | 1. Marchetti S, de Vries NA, Buckle T, Bolijn MJ, van Eijndhoven MA, Beijnen JH, Mazzanti R, van Tellingen O, Schellens JH. Effect of the ATP-binding cassette drug transporters ABCB1, ABCG2, and ABCC2 on erlotinib hydrochloride (Tarceva) disposition in in vitro and in vivo pharmacokinetic studies employing Bcrp1-/-/Mdr1a/1b-/- (triple-knockout) and wild-type mice. Mol Cancer Ther. 2008 Aug;7(8):2280-7. doi: 10.1158/1535-7163.MCT-07-2250. PMID: 18723475. 2. Moyer JD, Barbacci EG, Iwata KK, Arnold L, Boman B, Cunningham A, DiOrio C, Doty J, Morin MJ, Moyer MP, Neveu M, Pollack VA, Pustilnik LR, Reynolds MM, Sloan D, Theleman A, Miller P. Induction of apoptosis and cell cycle arrest by CP-358,774, an inhibitor of epidermal growth factor receptor tyrosine kinase. Cancer Res. 1997 Nov 1;57(21):4838-48. PMID: 9354447. |
| In vivo protocol: | 1. Marchetti S, de Vries NA, Buckle T, Bolijn MJ, van Eijndhoven MA, Beijnen JH, Mazzanti R, van Tellingen O, Schellens JH. Effect of the ATP-binding cassette drug transporters ABCB1, ABCG2, and ABCC2 on erlotinib hydrochloride (Tarceva) disposition in in vitro and in vivo pharmacokinetic studies employing Bcrp1-/-/Mdr1a/1b-/- (triple-knockout) and wild-type mice. Mol Cancer Ther. 2008 Aug;7(8):2280-7. doi: 10.1158/1535-7163.MCT-07-2250. PMID: 18723475. |
1: Gao JW, Zhan P, Qiu XY, Jin JJ, Lv TF, Song Y. Erlotinib-based doublet targeted therapy versus erlotinib alone in previously treated advanced non-small-cell lung cancer: a meta-analysis from 24 randomized controlled trials. Oncotarget. 2017 May 31;8(42):73258-73270. doi: 10.18632/oncotarget.18319. eCollection 2017 Sep 22. Review. PubMed PMID: 29069867; PubMed Central PMCID: PMC5641210.
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7: Xu W, Gong Y, Kuang M, Wu P, Cao C, Chen J, Tang C. Survival Benefit and Safety of Bevacizumab in Combination with Erlotinib as Maintenance Therapy in Patients with Metastatic Colorectal Cancer: A Meta-Analysis. Clin Drug Investig. 2017 Feb;37(2):155-165. doi: 10.1007/s40261-016-0465-0. Review. PubMed PMID: 27665469.
8: Gass-Jégu F, Gschwend A, Gairard-Dory AC, Mennecier B, Tebacher-Alt M, Gourieux B, Quoix É. Gastrointestinal perforations in patients treated with erlotinib: A report of two cases with fatal outcome and literature review. Lung Cancer. 2016 Sep;99:76-8. doi: 10.1016/j.lungcan.2016.06.012. Epub 2016 Jun 14. Review. PubMed PMID: 27565918.
9: Zhang S, Mao XD, Wang HT, Cai F, Xu J. Efficacy and safety of bevacizumab plus erlotinib versus bevacizumab or erlotinib alone in the treatment of non-small-cell lung cancer: a systematic review and meta-analysis. BMJ Open. 2016 Jun 30;6(6):e011714. doi: 10.1136/bmjopen-2016-011714. Review. PubMed PMID: 27363819; PubMed Central PMCID: PMC4932259.
10: Wang Y, Hu GF, Zhang QQ, Tang N, Guo J, Liu LY, Han X, Wang X, Wang ZH. Efficacy and safety of gemcitabine plus erlotinib for locally advanced or metastatic pancreatic cancer: a systematic review and meta-analysis. Drug Des Devel Ther. 2016 Jun 13;10:1961-72. doi: 10.2147/DDDT.S105442. eCollection 2016. Review. PubMed PMID: 27358556; PubMed Central PMCID: PMC4912328.
11: Zheng MH, Sun HT, Xu JG, Yang G, Huo LM, Zhang P, Tian JH, Yang KH. Combining Whole-Brain Radiotherapy with Gefitinib/Erlotinib for Brain Metastases from Non-Small-Cell Lung Cancer: A Meta-Analysis. Biomed Res Int. 2016;2016:5807346. doi: 10.1155/2016/5807346. Epub 2016 Feb 24. Review. PubMed PMID: 27006948; PubMed Central PMCID: PMC4783530.
12: Brower JV, Robins HI. Erlotinib for the treatment of brain metastases in non-small cell lung cancer. Expert Opin Pharmacother. 2016;17(7):1013-21. doi: 10.1517/14656566.2016.1165206. Epub 2016 Mar 30. Review. PubMed PMID: 26967582.
13: Awad R, Nott L. Radiation recall pneumonitis induced by erlotinib after palliative thoracic radiotherapy for lung cancer: Case report and literature review. Asia Pac J Clin Oncol. 2016 Mar;12(1):91-5. doi: 10.1111/ajco.12447. Epub 2016 Feb 5. Review. PubMed PMID: 26846159.
14: Jensen LH. Clinical aspects and perspectives of erlotinib in the treatment of patients with biliary tract cancer. Expert Opin Investig Drugs. 2016;25(3):359-65. doi: 10.1517/13543784.2016.1142973. Epub 2016 Feb 6. Review. PubMed PMID: 26781267.
15: Ma H, Tian X, Zeng XT, Zhang Y, Wang Y, Wang F, Zhou JG. The Efficacy of Erlotinib Versus Conventional Chemotherapy for Advanced Nonsmall-Cell Lung Cancer: A PRISMA-Compliant Systematic Review With Meta-Regression and Meta-Analysis. Medicine (Baltimore). 2016 Jan;95(2):e2495. doi: 10.1097/MD.0000000000002495. Review. PubMed PMID: 26765461; PubMed Central PMCID: PMC4718287.
16: Zhou JG, Tian X, Cheng L, Zhou Q, Liu Y, Zhang Y, Bai YJ, Ma H. The Risk of Neutropenia and Leukopenia in Advanced Non-Small Cell Lung Cancer Patients Treated With Erlotinib: A Prisma-Compliant Systematic Review and Meta-Analysis. Medicine (Baltimore). 2015 Oct;94(40):e1719. doi: 10.1097/MD.0000000000001719. Review. Erratum in: Medicine (Baltimore). 2015 Dec;94(51):e003b. PubMed PMID: 26448029; PubMed Central PMCID: PMC4616758.
17: Xu JL, Jin B, Ren ZH, Lou YQ, Zhou ZR, Yang QZ, Han BH. Chemotherapy plus Erlotinib versus Chemotherapy Alone for Treating Advanced Non-Small Cell Lung Cancer: A Meta-Analysis. PLoS One. 2015 Jul 6;10(7):e0131278. doi: 10.1371/journal.pone.0131278. eCollection 2015. Review. PubMed PMID: 26147288; PubMed Central PMCID: PMC4493135.
18: Greenhalgh J, Bagust A, Boland A, Dwan K, Beale S, Hockenhull J, Proudlove C, Dundar Y, Richardson M, Dickson R, Mullard A, Marshall E. Erlotinib and gefitinib for treating non-small cell lung cancer that has progressed following prior chemotherapy (review of NICE technology appraisals 162 and 175): a systematic review and economic evaluation. Health Technol Assess. 2015 Jun;19(47):1-134. doi: 10.3310/hta19470. Review. PubMed PMID: 26134145; PubMed Central PMCID: PMC4781386.
19: Ellis PM, Coakley N, Feld R, Kuruvilla S, Ung YC. Use of the epidermal growth factor receptor inhibitors gefitinib, erlotinib, afatinib, dacomitinib, and icotinib in the treatment of non-small-cell lung cancer: a systematic review. Curr Oncol. 2015 Jun;22(3):e183-215. doi: 10.3747/co.22.2566. Review. PubMed PMID: 26089730; PubMed Central PMCID: PMC4462541.
20: Landi L, Cappuzzo F. Experience with erlotinib in the treatment of non-small cell lung cancer. Ther Adv Respir Dis. 2015 Aug;9(4):146-63. doi: 10.1177/1753465815588053. Epub 2015 Jun 10. Review. PubMed PMID: 26063687.
