1058132-82-3

Basic information

• Product Name: Erlotinib IMpurity A
• Synonyms: Erlotinib IMpurity A;4-Quinazolinamine,N-(3-ethenylphenyl)-6,7-bis(2-methoxyethoxy)-;Erlotinib-3-vinyl Hydrochloride 2
• CAS NO: 1058132-82-3
• Molecular Formula: C22H25N3O4
• Molecular Weight: 395.4516
• EINECS: -0
• Mol File: 1058132-82-3.mol
• Article Data: 1

Chemical Properties

• Appearance: /
• CAS DataBase Reference: Erlotinib IMpurity A(CAS DataBase Reference)
• NIST Chemistry Reference: Erlotinib IMpurity A(1058132-82-3)
• EPA Substance Registry System: Erlotinib IMpurity A(1058132-82-3)

Safety Data

• Hazardous Substances Data: 1058132-82-3(Hazardous Substances Data)

Upstream product

• 183321-74-6 erlotinib 

Relevant articles and documents

Identification of ketene-reactive intermediate of erlotinib possibly responsible for inactivation of P450 enzymes

Erlotinib (ELT), a tyrosine kinase inhibitor, is widely used for the treatment of nonsmall cell lung cancer in clinic. Unfortunately, severe drug-induced liver injury and other adverse effects occurred during the treatment. Meanwhile, ELT has been reported to be a mechanism-based inactivator of cytochrome P450(CYPs) 3A4 and 3A5. The objectives of this study were to identify ketene intermediate of ELT and investigate the association of the acetylenic bioactivation with the enzyme inactivation caused by ELT. A ketene intermediate was detected in human microsomal incubations of ELT, using 4-bromobenzylamine as a trapping agent. CYPs 3A4 and 3A5 mainly contributedtothe bioactivation of ELT. Microsomal incubation study showed that the ketene intermediate covalently modified the enzyme protein at lysine residues and destroyed the structure of heme. The vinyl and ethyl analogs of ELT showed minor enzyme inhibitory effect (less than 20%), whereas ELT inactivated more than 60% of the enzyme. The present study providedanovel bioactivation pathway of ELT and facilitated the understanding of the mechanisms of ELT-induced mechanism-based enzyme inactivation and liver injury.