产品
编 号：F061345
分子式：C28H31F3N4O6
分子量：576.56
分子式：C28H31F3N4O6
分子量：576.56
产品类型
规格
价格
是否有货
5mg
询价
询价
10mg
询价
询价
25mg
询价
询价
结构图
CAS No: 1186231-83-3
产品详情
生物活性：
TAK-441 is a highly potent and orally active hedgehog (Hh) signaling inhibitor with an IC50value of 4.4 nM. TAK-441 has strong antitumor activity in solid tumors.
体内研究：
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 (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 (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. Pharmacokinetic Parameters of TAK-441 in BALB/c-nu/nu mice (oral and Alzet infusion administration; 100 mg/kg; single).CompdMouse PK 10mg/kgMouse PK 100mg/kg
Cmax (lg/mL)AUC (lgh/mL)Cmax (lg/mL)AUC (lgh/mL)
12.6512.13.6332.3
11d5.6228.321.5206
Animal Model:rats and dogs
Dosage:1 mg/kg, 10 mg/kg
Administration:iv, 1 mg/kg; po, 10 mg/kg
Result:CompdMouse PK 10mg/kg
Vss(mL/kg)CL (mL/h/kg)AUC0–24h,iv(ng h/mL)AUC0–24h,po(ng h/mL)F (%)
Rat681.6 ± 81.6397.9 ± 10.12532.3 ± 69.18031.8 ± 1218.631.7
Dog2181.3 ± 82.8161.3 ± 35.65101.5 ± 685.545405.6 ± 5812.090.3 ± 8.8
Animal Model:BALB/c-nu/nu mice
Dosage:10 mg/kg, 100 mg/kg
Administration:oral; 10 mg/kg, 100 mg/kg
Result:Inhibits Gli1 mRNA in the tumor and skin with IC50 values of 0.0457 mg/mL and 0.113 mg/mL, respectively.
Animal Model: Ptc1+/-p53-/- mice
Dosage:1 and 25 mg/kg
Administration:oral, 1 and 25 mg/kg, QD for 14 days
Result:Showed strong antitumor activity and resulted in a dose-dependent PK profile by improving solubility.
体外研究：
TAK-441 (compound 11d) (0.03–1000 nM, 48 h) has potent activity in the Gli-luc reporter with an IC50 value of 4.4 nM and good solubility. TAK-441 (0.03–1000 nM, 48 h) inhibits Gli1 mRNA with IC50 values of 0.0457 and 0.113 mg/mlin the tumor and skin, respectively. TAK-441 (0.5-500 nM, 48-72 h) does not affect androgen withdrawal-induced Shh up-regulation or viability of LNCaP cells. TAK-441 (0.5-500 nM, 48-72 h) leads to delayed castration-resistant progression of LNCaP xenografts by disrupting paracrine Hh signaling with the tumor stroma.
TAK-441 is a highly potent and orally active hedgehog (Hh) signaling inhibitor with an IC50value of 4.4 nM. TAK-441 has strong antitumor activity in solid tumors.
体内研究：
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 (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 (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. Pharmacokinetic Parameters of TAK-441 in BALB/c-nu/nu mice (oral and Alzet infusion administration; 100 mg/kg; single).CompdMouse PK 10mg/kgMouse PK 100mg/kg
Cmax (lg/mL)AUC (lgh/mL)Cmax (lg/mL)AUC (lgh/mL)
12.6512.13.6332.3
11d5.6228.321.5206
Animal Model:rats and dogs
Dosage:1 mg/kg, 10 mg/kg
Administration:iv, 1 mg/kg; po, 10 mg/kg
Result:CompdMouse PK 10mg/kg
Vss(mL/kg)CL (mL/h/kg)AUC0–24h,iv(ng h/mL)AUC0–24h,po(ng h/mL)F (%)
Rat681.6 ± 81.6397.9 ± 10.12532.3 ± 69.18031.8 ± 1218.631.7
Dog2181.3 ± 82.8161.3 ± 35.65101.5 ± 685.545405.6 ± 5812.090.3 ± 8.8
Animal Model:BALB/c-nu/nu mice
Dosage:10 mg/kg, 100 mg/kg
Administration:oral; 10 mg/kg, 100 mg/kg
Result:Inhibits Gli1 mRNA in the tumor and skin with IC50 values of 0.0457 mg/mL and 0.113 mg/mL, respectively.
Animal Model: Ptc1+/-p53-/- mice
Dosage:1 and 25 mg/kg
Administration:oral, 1 and 25 mg/kg, QD for 14 days
Result:Showed strong antitumor activity and resulted in a dose-dependent PK profile by improving solubility.
体外研究：
TAK-441 (compound 11d) (0.03–1000 nM, 48 h) has potent activity in the Gli-luc reporter with an IC50 value of 4.4 nM and good solubility. TAK-441 (0.03–1000 nM, 48 h) inhibits Gli1 mRNA with IC50 values of 0.0457 and 0.113 mg/mlin the tumor and skin, respectively. TAK-441 (0.5-500 nM, 48-72 h) does not affect androgen withdrawal-induced Shh up-regulation or viability of LNCaP cells. TAK-441 (0.5-500 nM, 48-72 h) leads to delayed castration-resistant progression of LNCaP xenografts by disrupting paracrine Hh signaling with the tumor stroma.
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