product name TAK-700 (Orteronel)
Description: TAK-700 (aslo known as Orteronel) is a potent and highly selective, orally bioavailable non-steroidal androgen synthesis inhibitor of human 17,20-lyase inhibitor with IC50 of 38 nM, it exhibits >1000-fold selectivity over other CYPs (e.g. 11-hydroxylase and CYP3A4). TAK-700 has potential antiandrogen activity by binding to and inhibiting the steroid 17alpha-monooxygenase in both the testes and adrenal glands, thereby inhibiting androgen production. This may decrease androgen-dependent growth signaling and may inhibit cell proliferation of androgen-dependent tumor cells.
References: Bioorg Med Chem. 2011 Nov 1;19(21):6383-99; J Steroid Biochem Mol Biol. 2012 Apr;129(3-5):115-28.
307.35
Formula
C18H17N3O2
CAS No.
426219-18-3
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 61 mg/mL (198.5 mM)
Water: <1 mg/mL
Ethanol: 8 mg/mL (26.0 mM)
Solubility (In vivo)
0.5% methylcellulose: 30 mg/mL
Synonyms
other peoduct :
| In Vitro |
In vitro activity: In vitro, TAK-700 shows the potent inhibitory activity against rat and human steroid 17,20-lyase with IC50 of 54 nM and 38 nM, respectively. While other CYP isoforms including 11-hydroxylase and CYP3A4 are not significantly affected by TAK-700. In microsomes expressing human CYP isoforms, TAK-700 exhibit greater inhibitory effects on 17,20-lyase with IC50 of 19 nM compared to the other CYP isoforms. TAK-700 shows the inhibitory activity against monkey 17,20-lyase and 17-hydroxylase with IC50 of 27 nM and 38 nM, respectively. In monkey adrenal cells, TAK-700 inhibits the ACTH stimulated production of DHEA and androstenedione with IC50 of 110 nM and 130 nM, respectively. Moreover, TAK-700 also potently inhibits DHEA production in human adrenocortical tumor line H295R cells with IC50 of 37 nM. Kinase Assay: Cell Assay: |
|---|---|
| In Vivo | In cynomolgus monkeys, oral treatment of TAK-700 at a dose of 1 mg/kg markedly reduces serum testosterone and dehydroepiandrosterone (DHEA) levels. Oral treatment of TAK-700 at a dose of 1 mg/kg results in favorable pharmacokinetic parameters with Tmax, Cmax, t1/2 and AUC0-24 hours of 1.7 hours, 0.147 μg/mL, 3.8 hours and 0.727 μg h/mL, respectively. |
| Animal model | Adult male cynomolgus monkeys. |
| Formulation & Dosage | Dissolved in 0.5% methylcellulose; ≤1 mg/kg; Oral gavage |
| References | Bioorg Med Chem. 2011 Nov 1;19(21):6383-99; J Steroid Biochem Mol Biol. 2012 Apr;129(3-5):115-28. |
