A nucleoside analog and prodrug form of 2-CdATP
Cladribine is an adenosine deaminase inhibitor.Adenosine deaminase is an enzyme that involved in purine metabolism.
Cladribine is a well-known purine nucleoside analog with particular activity against lymphoproliferative disorders, such as hairy cell leukemia (HCL). In U266, RPMI8226 and MM1.S cells, Cladribine inhibited cell proliferation in a dose-dependant way with IC50 value of 2.43, 0.75 and 0.18 μmol/L, respectively. Apoptosis assays showed that Cladribine induced apoptosis of U266, RPMI8226 and MM1.S cells in a dose-dependant way [1]. In MM1.S cells, Cladribine (0.2uM) induces activation of caspase-3, -8, and -9 and PARP cleavage in a time-dependent way and reduces the phospho-STAT3 levels in a dose-dependent way. Also, Cladribine induces accumulation of DNA strand breaks and then activates the tumor suppressor p53 in lymphocytes [1].
In the treatment of indolent lymphoid malignancies, lower doses of Cladribine (5 mg/m2/week) are highly active and possibly better tolerated than standard doses [2].
参考文献:
[1]. Ma J, Wang S, Zhao M, et al. Therapeutic potential of cladribine in combination with STAT3 inhibitor against multiple myeloma. BMC Cancer, 2011, 11: 255.
[2]. Robak T, Korycka A, Robak E. Older and new formulations of cladribine. Pharmacology and clinical efficacy in hematological malignancies. Recent Pat Anticancer Drug Discov, 2006, 1(1): 23-38.
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