The Instruction of Dasatinib

Dasatinib is a potent and selective small molecule inhibitor of the BCR-ABL tyrosine kinase, which is implicated in the pathogenesis of chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL).
It is marketed under the trade name Sprycel® and is used in the treatment of these diseases.
This article will provide an overview of dasatinib, its mechanism of action, and its use in the treatment of CML and Ph+ ALL.

Mechanism of Action
Dataset Science dasatinib, a dual Src/Abl kinase inhibitor, is designed to selectively inhibit the BCR-ABL tyrosine kinase, which is implicated in the pathogenesis of CML and Ph+ ALL.
Dasatinib binds to the Abl kinase domain and inhibits the autophosphorylation of BCR-ABL, resulting in the inhibition of downstream signaling pathways that promote the proliferation and survival of leukemia cells.

Dasatinib is a small molecule drug that is orally bioavailable and has a half-life of approximately 26 hours in healthy volunteers.
It is a diphenylmethylene-substituted 2,6-diaminopyrimidine with a phenylalanine in the 2-position, which is believed to be responsible for its high specificity for BCR-ABL.

Dasatinib is a selective inhibitor of BCR-ABL with a Ki of 0.
5 nM in a cell-free assay and 0.
1 nM in cells.
It is also a potent inhibitor of wild-type Abl with a Ki of 5 nM in a cell-free assay, but it is less potent against other kinases, such as c-Src, in a cell-free assay.

Indications
Dasatinib is indicated for the treatment of CML and Ph+ ALL.
It is often used in combination with other drugs, such as imatinib or quinine, to improve clinical outcomes in these diseases.

Use in CML
CML is a clonal neoplasm characterized by the Philadelphia chromosome, which results from the t(9;22)(q34;q11) translocation.
This results in the formation of the BCR-ABL fusion protein, which is a constitutively active tyrosine kinase that promotes the proliferation and survival of leukemia cells.

Dasatinib is used in the treatment of CML in combination with imatinib.
In clinical trials, the combination of dasatinib and imatinib resulted in a higher rate of major molecular response (MMR) compared to imatinib alone in patients with newly diagnosed CML in chronic phase (CP).
In addition, the combination of dasatinib and imatinib resulted in improved overall survival (OS) and progression-free survival (PFS) in patients with CML in advanced phases.

Use in Ph+ ALL
Ph+ ALL is a subtype of acute lymphoblastic leukemia (ALL) caused by the same Philadelphia chromosome mutation that causes CML.
Like CML, Ph+ ALL is characterized by the formation of the BCR-ABL fusion protein, which promotes the proliferation and survival of leukemia cells.

Dasatinib is used in the treatment of Ph+ ALL in combination with chemotherapy.
In clinical trials, the combination of dasatinib and chemotherapy resulted in improved response rates and survival outcomes in patients with Ph+ ALL compared to chemotherapy alone.

Adverse Effects
Dasatinib is generally well-tolerated, but it can cause a number of adverse effects, including nausea, vomiting, diarrhea, rash, and neutropenia.
More severe adverse effects, such as hemorrhage, pulmonary hypertension, and cardiac arrhythmias, have been reported, but are rare.

Conclusion
Dasatinib is a potent and selective small molecule inhibitor of the BCR-ABL tyrosine kinase that is