A Comprehensive Monograph on Bosutinib (DB06616): From Molecular Design to Clinical Application in Chronic Myelogenous Leukemia

Section 1: Introduction and Overview of Bosutinib

1.1 Executive Summary

Bosutinib is an orally administered, second-generation small molecule drug classified as a tyrosine kinase inhibitor (TKI).[1] It is marketed globally under the brand name Bosulif® by Pfizer, following its initial synthesis and development by Wyeth.[2] The medication holds a distinct and important position in the therapeutic armamentarium for Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML), a hematologic malignancy driven by the aberrant BCR-ABL fusion protein.[1]

The pharmacological distinction of bosutinib lies in its mechanism as a potent, dual inhibitor that targets both the primary pathogenic driver of CML, the BCR-ABL kinase, and members of the SRC-family of kinases (SFKs).[6] This dual inhibitory activity provides a broader spectrum of action compared to first-generation TKIs and contributes to its efficacy in patient populations that have developed resistance to prior therapies.[9]

Its primary approved indications span the treatment of adult and, more recently, pediatric patients with Ph+ CML.[6] It is utilized in both newly diagnosed patients and those who have demonstrated resistance or intolerance to previous TKI therapies.[5] The clinical profile of bosutinib is characterized by robust efficacy and a unique, manageable toxicity profile. The most notable adverse events are a high incidence of early-onset, low-grade gastrointestinal toxicities, particularly diarrhea. However, this is counterbalanced by a comparatively lower risk of the serious cardiovascular and vascular adverse events that are associated with other second-generation TKIs, a feature that significantly influences its placement in clinical practice.[12]

1.2 The Evolving Role of Bosutinib in CML Therapy