Chemical structural formula analysis of pyrotinib/arini

Pyrotinib Maleate (Pyrotinib Maleate) is a small molecule irreversible inhibitor of tyrosine kinase, and its English name is Pyrotinib Maleate Tablets. Its molecular formula is C27H27N5O3·C4H4O4 (maleate form), which is a highly selective dual-target inhibitor of HER2 and EGFR. Its chemical structure design takes into account drug targeting, oral bioavailability and metabolic stability. It is an innovative molecule formed through medicinal chemistry optimization.

Structurally, pyrotinib contains a pyrrole ring, phenyl substituent and nitrogen-containing heterocycle. These structural features help enhance the binding ability to the ATP binding site of HER2 tyrosine kinase and form an irreversible covalent bond, allowing the drug to inhibit receptor activity for a long time. The phenyl substituent can improve the lipophilicity of the drug, thus improving its ability to penetrate cell membranes and facilitating oral absorption. In addition, the maleate portion of the pyrotinib molecule not only improves water solubility, but also contributes to the stability and bioavailability of oral dosage forms.

From a pharmacological mechanism, pyrotinib binds to the tyrosine kinase domains of HER2 and EGFR, blocks receptor autophosphorylation, inhibits the activation of downstream PI3K/AKT and MAPK signaling pathways, and ultimately inhibits tumor cell proliferation and induces apoptosis. This irreversible inhibitory mechanism has a longer duration of action and a lower incidence of drug resistance than reversible inhibitors. In addition, the inhibitory effect of pyrotinib on EGFR can synergistically inhibit the proliferation of HER2-positive tumors and improve clinical efficacy.

The chemical design of pyrotinib also takes into account the balance between selectivity and safety. It can minimize the impact on normal tissues of the heartHER2 and reduce the risk of cardiotoxicity. In preclinical studies, pyrotinib showed high selectivity and differentiated cytotoxicity, which was helpful in reducing adverse reactions in normal tissues.

Reference materials:https://synapse.patsnap.com/article/what-is-pyrotinib-maleate-used-for