Allitinib tosylate

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Description:Allitinib, also known as AST1306 and ALS 1306, is a potent, selective, irreversible ErbB2 and EGFR inhibitor. AST-1306 inhibits the enzymatic activities of wild-type epidermal growth factor receptor (EGFR) and ErbB2 as well as EGFR resistant mutant in both cell-free and cell-based systems. AST1306 was found to function as an irreversible inhibitor, most likely through covalent interaction with Cys797 and Cys805 in the catalytic domains of EGFR and ErbB2, respectively. In vivo, AST1306 potently suppressed tumor growth in ErbB2-overexpressing adenocarcinoma xenograft and FVB-2/N(neu) transgenic breast cancer mouse models, but weakly inhibited the growth of EGFR-overexpressing tumor xenografts.

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Chemical Structure

Theoretical Analysis

MedKoo Cat#: 401070Name: Allitinib tosylateCAS#: 1050500-29-2 (tosylate)Chemical Formula: C31H26ClFN4O5SExact Mass: Molecular Weight: 621.0804Elemental Analysis: C, 59.95; H, 4.22; Cl, 5.71; F, 3.06; N, 9.02; O, 12.88; S, 5.16

Related CAS #:897383-62-9 (free base)1050500-29-2 (tosylate)1050500-25-8 (HCl)1050500-27-0 (phosphate)1050500-30-5 (mesylate)1050500-33-8 (oxalate)1050500-34-9 (acetate)1050500-46-3 (HBr)

Synonym:Allitinib tosylate; AST1306 TsOH; AST-1306 TsOH; AST 1306 TsOH; ALS1306 TsOH; ALS-1306 TsOH; ALS1306 TsOH; AST 6 TsOH; AST-6 TsOH; AST6 TsOH.

IUPAC/Chemical Name:N-[4-[[3-Chloro-4-[(3-fluorobenzyl)oxy]phenyl]amino]quinazolin-6-yl]acrylamide tosylate

InChi Key:ZMUKJEHWLJBODV-UHFFFAOYSA-N

InChi Code:InChI=1S/C24H18ClFN4O2.C7H8O3S/c1-2-23(31)29-17-6-8-21-19(11-17)24(28-14-27-21)30-18-7-9-22(20(25)12-18)32-13-15-4-3-5-16(26)10-15;1-6-2-4-7(5-3-6)11(8,9)10/h2-12,14H,1,13H2,(H,29,31)(H,27,28,30);2-5H,1H3,(H,8,9,10)

SMILES Code:C=CC(NC1=CC2=C(NC3=CC=C(OCC4=CC=CC(F)=C4)C(Cl)=C3)N=CN=C2C=C1)=O.OS(=O)(C5=CC=C(C)C=C5)=O

Technical Data

Additional Information

References

1: Xu J, Gong L, Qian Z, Song G, Liu J. ERBB4 promotes the proliferation of gastric cancer cells via the PI3K/Akt signaling pathway. Oncol Rep. 2018 Jun;39(6):2892-2898. doi: 10.3892/or.2018.6343. Epub 2018 Mar 30. PMID: 29620274.

2: Song G, Zhang H, Chen C, Gong L, Chen B, Zhao S, Shi J, Xu J, Ye Z. miR-551b regulates epithelial-mesenchymal transition and metastasis of gastric cancer by inhibiting ERBB4 expression. Oncotarget. 2017 Jul 11;8(28):45725-45735. doi: 10.18632/oncotarget.17392. PMID: 28501849; PMCID: PMC5542221.

3: Silva-Oliveira RJ, Melendez M, Martinho O, Zanon MF, de Souza Viana L, Carvalho AL, Reis RM. AKT can modulate the in vitro response of HNSCC cells to irreversible EGFR inhibitors. Oncotarget. 2017 Jun 7;8(32):53288-53301. doi: 10.18632/oncotarget.18395. PMID: 28881811; PMCID: PMC5581110.

4: Martinho O, Silva-Oliveira R, Cury FP, Barbosa AM, Granja S, Evangelista AF, Marques F, Miranda-Gonçalves V, Cardoso-Carneiro D, de Paula FE, Zanon M, Scapulatempo-Neto C, Moreira MA, Baltazar F, Longatto-Filho A, Reis RM. HER Family Receptors are Important Theranostic Biomarkers for Cervical Cancer: Blocking Glucose Metabolism Enhances the Therapeutic Effect of HER Inhibitors. Theranostics. 2017 Jan 15;7(3):717-732. doi: 10.7150/thno.17154. PMID: 28255362; PMCID: PMC5327645.

5: Silva-Oliveira RJ, Silva VA, Martinho O, Cruvinel-Carloni A, Melendez ME, Rosa MN, de Paula FE, de Souza Viana L, Carvalho AL, Reis RM. Cytotoxicity of allitinib, an irreversible anti-EGFR agent, in a large panel of human cancer- derived cell lines: KRAS mutation status as a predictive biomarker. Cell Oncol (Dordr). 2016 Jun;39(3):253-63. doi: 10.1007/s13402-016-0270-z. Epub 2016 Feb 26. PMID: 26920031.

6: Jiang JF, Chen XY, Zhong DF. [Metabolic research of domestically developed small molecule tyrosine kinase inhibitors]. Yao Xue Xue Bao. 2016 Feb;51(2):248-56. Chinese. PMID: 29856578.

7: Zhang H, Wang YJ, Zhang YK, Wang DS, Kathawala RJ, Patel A, Talele TT, Chen ZS, Fu LW. AST1306, a potent EGFR inhibitor, antagonizes ATP-binding cassette subfamily G member 2-mediated multidrug resistance. Cancer Lett. 2014 Aug 1;350(1-2):61-8. doi: 10.1016/j.canlet.2014.04.008. Epub 2014 Apr 18. PMID: 24747122.

8: Zhang J, Cao J, Li J, Zhang Y, Chen Z, Peng W, Sun S, Zhao N, Wang J, Zhong D, Zhang X, Zhang J. A phase I study of AST1306, a novel irreversible EGFR and HER2 kinase inhibitor, in patients with advanced solid tumors. J Hematol Oncol. 2014 Mar 11;7:22. doi: 10.1186/1756-8722-7-22. PMID: 24612546; PMCID: PMC4007625.

9: Lin L, Xie C, Gao Z, Chen X, Zhong D. Metabolism and pharmacokinetics of allitinib in cancer patients: the roles of cytochrome P450s and epoxide hydrolase in its biotransformation. Drug Metab Dispos. 2014 May;42(5):872-84. doi: 10.1124/dmd.113.056341. Epub 2014 Mar 5. PMID: 24598282.

10: Lin L, Gao Z, Chen X, Zhong D. Development and validation of a sensitive LC- MS/MS assay for the simultaneous quantification of allitinib and its two metabolites in human plasma. J Pharm Biomed Anal. 2013 Dec;86:49-55. doi: 10.1016/j.jpba.2013.07.003. Epub 2013 Jul 19. PMID: 23973791.

11: Xie H, Lin L, Tong L, Jiang Y, Zheng M, Chen Z, Jiang X, Zhang X, Ren X, Qu W, Yang Y, Wan H, Chen Y, Zuo J, Jiang H, Geng M, Ding J. AST1306, a novel irreversible inhibitor of the epidermal growth factor receptor 1 and 2, exhibits antitumor activity both in vitro and in vivo. PLoS One. 2011;6(7):e21487. doi: 10.1371/journal.pone.0021487. Epub 2011 Jul 18. PMID: 21789172; PMCID: PMC3138742.