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TAK-441

CAS No. : 1186231-83-3

MCE 站：TAK-441

产品活性：TAK-441 (compound 11d) 是一种高效的口服 hedgehog (Hh) 信号抑制剂，其IC₅₀值为 4.4 nM，。TAK-441 (compound 11d) 具有较强的抗肿瘤活性。

研究领域：Stem Cell/Wnt

作用靶点：Hedgehog

In Vitro: TAK-441 (compound 11d) has potent activity in the Gli-luc reporter with an IC₅₀ value of 4.4 nM ａnd good solubility. TAK-441 inhibits Gli1 mRNA with IC₅₀ values of 0.0457 ａnd 0.113 mg/ml in the tumor ａnd skin, respectively. TAK-441 does not affect androgen withdrawal-induced Shh up-regulation orviability of LNCaP cells. TAK-441 leads to delayed castration-resistant progression of LNCaP xenografts by disrupting paracrine Hh signaling with the tumor stroma.

In Vivo: TAK-441 (compound 11d) (oral; 10 mg/kg, 100 mg/kg) has favorable exposure ａnd good oral absorption in BALB/c-nu/nu mice.
TAK-441 (compound 11d) (oral, 1 ａnd 25 mg/kg, QD for 14 days) has strong antitumor activity ａnd can achieve dose-dependent plasma ａnd tumor concentrations by improving the solubility of TAK-441 in Ptc1^+/-p53^-/- mice bearing medulloblastoma allografts.
TAK-441 (compound 11d) (iv, 1 mg/kg; po, 10 mg/kg) is able to achieve sufficient exposure following oral administration in rats ａnd dogs.TAK-441 (oral; 1, 10, ａnd 25 mg/kg) shows dose-dependent antitumor activity in xenografted mice, the IC₅₀ value for the tumor growth inhibition is 0.075 mg/ml. TAK-441 (oral ａnd Alzet infusion administration; 100 mg/kg; single) inhibits Gli1 mRNA in the tumor ａnd skin with IC₅₀ values of 0.0457 mg/ml ａnd 0.113 mg/ml, respectively.

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