Dasatinib

Dasatinib is a potent, orally active small-molecule inhibitor of multiple tyrosine kinases, including Bcr-Abl, Src family kinases, c-Kit, PDGFR, and EphA2. It inhibits Src, Abl, Lck, and c-Kit with an IC₅₀ of 0.8 nM, 1 nM, 0.4 nM, and 79 nm, respectively. Originally developed as a second-generation treatment for chronic myeloid leukemia (CML), it is widely used in cancer research and cell signaling studies due to its broad kinase inhibition profile.

Key features and applications include:

• Multi-Targeted Inhibition: Blocks both receptor and non-receptor tyrosine kinases, including drug-resistant Bcr-Abl mutants.
• Cancer Research: Used to study leukemia, solid tumors, and kinase-driven malignancies.
• Cell Signaling Studies: Investigates pathways involving Src, Abl, and PDGFR signaling.
• Immunology: Modulates T-cell activation and natural killer (NK) cell function.
• Fibrosis Models: Explored for its anti-fibrotic effects in liver and lung disease models.
• Autophagy & Apoptosis: Induces programmed cell death and autophagy in various cancer cell lines.

Relevant disease states include:

• Chronic Myeloid Leukemia (CML): FDA-approved for treatment of CML, especially in cases resistant to imatinib.
• Acute Lymphoblastic Leukemia (ALL): Effective in Philadelphia chromosome-positive (Ph+) ALL.
• Solid Tumors: Investigated in breast, prostate, and pancreatic cancers for its anti-proliferative effects.
• Fibrotic Diseases: Studied for its potential to reduce fibrosis by targeting PDGFR and Src pathways.
• Neurodegenerative Disorders: Explored for neuroprotective effects via modulation of kinase signaling.