Allitinib tosylate
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MedKoo CAT#: 401070

CAS#: 1050500-29-2 (tosylate)

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.


Chemical Structure

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Allitinib tosylate
CAS# 1050500-29-2 (tosylate)

Theoretical Analysis

MedKoo Cat#: 401070
Name: Allitinib tosylate
CAS#: 1050500-29-2 (tosylate)
Chemical Formula: C31H26ClFN4O5S
Exact Mass:
Molecular Weight: 621.0804
Elemental Analysis: C, 59.95; H, 4.22; Cl, 5.71; F, 3.06; N, 9.02; O, 12.88; S, 5.16

Price and Availability

Size Price Availability Quantity
5.0mg USD 150.0 Same day
10.0mg USD 250.0 Same day
25.0mg USD 450.0 Same day
50.0mg USD 750.0 Same day
100.0mg USD 1150.0 Same day
200.0mg USD 1850.0 Same day
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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

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, not in water

Shelf Life: >5 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

Biological target: Allitinib tosylate is an EGFR and ErbB2 inhibitor with IC50s of 0.5 and 3 nM, respectively.
In vitro activity: The antiproliferative effects of AST1306 were evaluated in a panel of human cancer cell lines with varying levels of EGFR and ErbB2 expression. As shown in Fig. 5A, AST1306 effectively suppressed the proliferation of human cancer cell lines; however, the IC50 values varied widely among them. The Calu-3 lung adenocarcinoma and BT474 breast cancer cell line, containing high levels of ErbB2, were more sensitive to AST1306, with IC50 values of 0.23 and 0.97 µmol/L, respectively. In contrast, cell lines with high levels of EGFR but lower levels of ErbB2 (MDA-MB-468, A549 and NCI-H23) or high levels of both ErbB2 and EGFR (SK-OV-3) were less sensitive to AST1306, with an IC50 values ranging from 6.2 to 7.5 µmol/L. The MCF-7 cell line, which expresses low levels of both EGFR and ErbB2, was the least sensitive to AST1306, with IC50 value of 16.0 µmol/L. These results indicate that AST1306 inhibits the proliferation of human cancer cell lines in vitro, and suggest that ErbB2 expression is associated with a consistently higher sensitivity to AST1306 across the various cell lines tested. Reference: Reference: PLoS One. 2011;6(7):e21487. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3138742/
In vivo activity: The antitumor activity of AST1306 was measured in two different human ovarian cancer xenograft nude mice models (SK-OV-3 and HO-8910), and two different human lung cancer xenograft nude mice models (Calu-3 and A549). As shown in Fig. 6A, twice daily oral administration of AST1306 caused a dramatic suppression of tumor growth in SK-OV-3 and Calu-3 xenograft models. In SK-OV-3 models, tumors almost completely disappeared after treatment with AST1306 for 7 d. In contrast, AST1306 only slightly suppressed tumor growth in HO-8910 and A549 xenograft models (Fig. 6A). These results demonstrate that the antitumor efficacy of AST1306 is greater in ErbB2-overexpressing tumor models than in models expressing low levels of ErbB2. Reference: PLoS One. 2011;6(7):e21487. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3138742/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 35.0 56.35
DMF 25.0 40.25
DMF:PBS (pH 7.2) (1:3) 0.25 0.4
Ethanol 1.0 1.61

Preparing Stock Solutions

The following data is based on the product molecular weight 621.0804 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.

Recalculate based on batch purity %
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. 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. 2. 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.
In vitro protocol: 1. 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.
In vivo protocol: 1. 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.

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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.



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