Pelitinib

Pelitinib is an orally active 3-cyanoquinoline inhibitor of the ErbB receptor tyrosine kinase family, with its strongest reported activity against EGFR. Identified by CAS 257933-82-7, it has the formula C24H23ClFN5O2 and a molecular weight of 467.92 g/mol. The scaffold combines an ATP-site-binding quinoline core with an electrophilic acrylamide group that enables covalent target engagement. Exposure time and post-washout recovery are therefore important variables when designing experiments with this compound.

Application of EKB-569

EKB-569 is used to investigate irreversible EGFR inhibition in biochemical assays, EGFR-dependent cancer cells, and tumor xenografts. It allows researchers to compare covalent and reversible inhibitors, measure how long receptor suppression persists after compound removal, and connect changes in EGFR phosphorylation with downstream proliferation signals. Its clinical-stage history also makes it a useful benchmark for assessing whether sustained target engagement translates into cellular and in vivo activity. It is intended for laboratory research only.

In Vitro

In biochemical assays, pelitinib inhibits EGFR with a reported IC50 of 38.5 nM and is approximately 30-fold less potent against ErbB2. Weaker inhibition has been reported for other kinases, including Src, c-Met, Raf, and CDK4. In EGFR-responsive A431 and MDA-MB-468 cells, it reduces EGF-induced receptor phosphorylation and suppresses proliferation.

Pelitinib is represented in the Protein Data Bank under ligand code 93J. For EKB-569 PDB searches, this is the identifier to use. Structural records should be checked at the complex level before attributing a specific binding pose or EGFR interaction pattern directly to pelitinib.

In Vivo

Oral dosing inhibited tumor growth in xenograft models derived from EGFR-overexpressing human cancer cells. In a Phase I trial in advanced solid tumors, the maximum tolerated dose was 75 mg once daily on continuous and intermittent schedules. Grade 3 diarrhea was dose-limiting; rash, nausea, and asthenia were also reported. No major objective responses occurred, although two patients had prolonged stable disease. The catalogue record associates the compound with PF-05230915, while clinical publications predominantly use EKB-569.

Biochemical and Physiological Actions

The Pelitinib irreversible EGFR inhibitor mechanism involves two coordinated steps. The quinoline scaffold positions the molecule in the ATP-binding site, while the electrophilic acrylamide enables irreversible covalent engagement of EGFR, commonly attributed to reaction with Cys797. This prevents receptor autophosphorylation and reduces RAS–RAF–MEK–ERK and PI3K–AKT signaling involved in cell proliferation and survival. Because target occupancy persists after free compound is removed, signaling recovery depends on receptor turnover and new protein synthesis.

Features and Benefits of Pelitinib

• Nanomolar EGFR potency with irreversible, time-dependent target engagement.
• Suitable for phosphorylation, proliferation, washout, and recovery experiments.
• Oral activity demonstrated in xenograft and early clinical studies.
• Defined formula, molecular weight, and searchable Pelitinib SMILES representation.
• Useful for structural comparisons, although an EKB-569 PDB result requires ligand-level verification before being cited as a direct pelitinib complex.