| Identification | Back Directory | [Name]
TAK-441 | [CAS]
1186231-83-3 | [Synonyms]
TAK-441
6-ethyl-N-[1-(2-hydroxyacetyl)piperidin-4-yl]-1-methyl-4-oxo-5-phenacyl-3-(2,2,2-trifluoroethoxy)pyrrolo[3,2-c]pyridine-2-carboxamide
1H-Pyrrolo[3,2-c]pyridine-2-carboxamide, 6-ethyl-4,5-dihydro-N-[1-(2-hydroxyacetyl)-4-piperidinyl]-1-methyl-4-oxo-5-(2-oxo-2-phenylethyl)-3-(2,2,2-trifluoroethoxy)- | [Molecular Formula]
C28H31F3N4O6 | [MDL Number]
MFCD25976857 | [MOL File]
1186231-83-3.mol | [Molecular Weight]
576.56 |
| Chemical Properties | Back Directory | [Boiling point ]
761.6±60.0 °C(Predicted) | [density ]
1.40±0.1 g/cm3(Predicted) | [form ]
Solid | [pka]
13.88±0.10(Predicted) | [color ]
Off-white to light yellow |
| Hazard Information | Back Directory | [Uses]
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[1][2][3]. | [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[1].
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[1].
TAK-441 (iv, 1 mg/kg; po, 10 mg/kg) is able to achieve sufficient exposure following oral administration in rats and dogs[1].
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[1].
Pharmacokinetic Parameters of TAK-441 in BALB/c-nu/nu mice (oral and Alzet infusion administration; 100 mg/kg; single)[1].
| Compd | | | Mouse PK 10mg/kg | | | | Mouse PK 100mg/kg | | | | Cmax (lg/mL) | | AUC (lgh/mL) | | Cmax (lg/mL) | | AUC (lgh/mL) | | 1 | | 2.65 | | 12.1 | | 3.63 | | 32.3 | | 11d | | 5.62 | | 28.3 | | 21.5 | | 206 | |
| Animal Model: | rats and dogs[1] | | Dosage: | 1 mg/kg, 10 mg/kg | | Administration: | iv, 1 mg/kg; po, 10 mg/kg | | Result: | | Compd | | | Mouse PK 10mg/kg | | | | Vss(mL/kg) | CL (mL/h/kg) | AUC0–24h,iv(ng h/mL) | AUC0–24h,po(ng h/mL) | F (%) | | Rat | 681.6 ± 81.6 | 397.9 ± 10.1 | 2532.3 ± 69.1 | 8031.8 ± 1218.6 | 31.7 | | Dog | 2181.3 ± 82.8 | 161.3 ± 35.6 | 5101.5 ± 685.5 | 45405.6 ± 5812.0 | 90.3 ± 8.8 | |
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| Animal Model: | BALB/c-nu/nu mice[1] | | 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[1] | | 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. |
| [References]
[1] Tomohiro Ohashi, et al. Discovery of the investigational drug TAK-441, a pyrrolo[3,2-c]pyridine derivative, as a highly potent and orally active hedgehog signaling inhibitor: modification of the core skeleton for improved solubility. Bioorg Med Chem. 2012 DOI:10.1016/j.bmc.2012.07.034
[2] Akifumi Kogame, et al. Pharmacokinetic and pharmacodynamic modeling of hedgehog inhibitor TAK-441 for the inhibition of Gli1 messenger RNA expression and antitumor efficacy in xenografted tumor model mice. Drug Metab Dispos DOI:10.1124/dmd.112.049650
[3] Naokazu Ibuki, et al. TAK-441, a novel investigational smoothened antagonist, delays castration-resistant progression in prostate cancer by disrupting paracrine hedgehog signaling. Int J Cancer. 2013 Oct 15;133(8):1955-66. DOI:10.1002/ijc.28193 |
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| Company Name: |
NCE Biomedical Co.,Ltd.
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| Tel: |
4000-027-021 |24 +86-13986109188 | +86-15623472865 | +81-08033611988 |
| Website: |
www.approvedhomemanagement.com/ShowSupplierProductsList15748/0.htm |
| Company Name: |
SPIRO PHARMA
|
| Tel: |
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| Website: |
www.spiropharma.com.cn |
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