ALLITINIB

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C24H18ClFN4O2
Molecular Weight	448.877
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

FC1=CC(COC2=CC=C(NC3=C4C=C(NC(=O)C=C)C=CC4=NC=N3)C=C2Cl)=CC=C1

InChI

InChIKey=MVZGYPSXNDCANY-UHFFFAOYSA-N

InChI=1S/C24H18ClFN4O2/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/h2-12,14H,1,13H2,(H,29,31)(H,27,28,30)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21789172
Curator's Comment: description was created based on several sources, including: https://www.ncbi.nlm.nih.gov/pubmed/24612546 | http://adisinsight.springer.com/drugs/800032292

AST-1306, also known as Allitinib, is an orally active potent, selective, irreversible inhibitor of the HER family of receptor tyrosine kinases. 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 potently suppressed tumor growth in ErbB2-overexpressing adenocarcinoma xenograft and FVB-2/N(neu) transgenic breast cancer mouse models. Allitinib is in Phase I clinical trial for the treatment of advanced solid tumors. Serious adverse effects detected were: diarrhea, dehydration and hyperbilirubinemia.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Epidermal growth factor receptor erbB1 58 Target ID: CHEMBL203 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21789172 \| https://www.ncbi.nlm.nih.gov/pubmed/24598282	Inhibitor 8297	0.5 nM [IC50]
Receptor protein-tyrosine kinase erbB-2 35 Target ID: CHEMBL1824 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21789172 \| https://www.ncbi.nlm.nih.gov/pubmed/24598282	Inhibitor 8297	3.0 nM [IC50]
Receptor protein-tyrosine kinase erbB-4 12 Target ID: CHEMBL3009 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21789172	Inhibitor 8297	0.8 nM [IC50]
Cytochrome P450 3A4/3A5 6 Target ID: CHEMBL2111472 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24598282	Substrate 661

Conditions

Condition	Modality	Targets	Highest Phase	Product
Advanced solid cancer 28 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24612546	Primary		Phase I 428	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
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.	2016 Jun	26920031

Patents

Sample Use Guides

In Vivo Use Guide

1000 mg three times daily

Route of Administration: Oral

In Vitro Use Guide

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 uM/L, respectively.

Name

Type

Language

ALLITINIB

Common Name

English

AST1306

Common Name

English

N-(4-((3-CHLORO-4-((3-FLUOROBENZYL)OXY)PHENYL)AMINO)QUINAZOLIN-6-YL)ACRYLAMIDE

Systematic Name

English