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Tinostamustine

CAS No. : 1236199-60-2

MCE 国际站：Tinostamustine

产品活性：Tinostamustine (EDO-S101) 是 HDAC 的广谱抑制剂；抑制 HDAC1，HDAC2 和 HDAC3 的 IC₅₀ 值分别为 6 nM，9 nM，9 nM 和 25 nM。

研究领域：Cell Cycle/DNA Damage  |  Epigenetics

作用靶点：HDAC

In Vitro: Tinostamustine inhibits HDAC activity in rat peripheral blood mononuclear cells (PBMCs) in a cellular assay by approximately 90% one hour after dosing with 10mg/kg i.v. HDAC inhibition in PBMCs could not be increased with higher doses up to 50mg/kg. Tinostamustine triggers apoptosis and shows strong antitumor activity in HL60 and Daudi cells. Initial in vitro experiments in HL60 cells shows an activation of the intrinsic pathway of apoptosis with cleavage of caspases 3, 9 and PARP and a marked reduction of anti-apoptotic proteins XIAP and Mcl-1.

In Vivo: Intracellular HDAC inhibition of Tinostamustine, which occurs rapidly after dosing is at maximum activity already at the lowest dose of 10mg/kg and lasts for about 12-16 hours. Exposure to Tinostamustine causes a strong DNA repair response evidenced by activation of pH2AX and p53 in tumors taken from mice bearing subcutaneous human Burkitt’s lymphoma. Tumors of BL rapidly shrink or are completely eradicated after i.v. administration of Tinostamustine.

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