JTT-654
JTT-654 is an orally active, potent and selective11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor. The IC50 of JTT-654 for 11β-HSD1 is 4.65, 0.97, and 0.74 nM in human, rat, and mouse recombinant enzymes, respectively. JTT-654 showed competitive inhibition against human recombinant enzyme. The IC50 value for human 11β-HSD2 is > 30 μM (human 11β-HSD2 is responsible for the reverse reaction against human 11β-HSD1). JTT-654 ameliorates insulin resistance and non-obese type 2 diabetes by inhibiting adipose tissue and liver 11β-HSD1.
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- No. CAS: 916828-66-5
- Fòrmula: C28H33F3N4O3
- Peso molecular:530.58
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Actividad biológica
Descripciòn
IC50 & Target
IC50: 4.65 ± 0.28 nM (human 11β-HSD1), 0.97 ± 0.019 nM (rat 11β-HSD1), 0.74 ± 0.050 nM (rat 11β-HSD1), > 30 μM (human 11β-HSD2)[1]
In Vitro
JTT-654 (0.1-10 μM, 24 h) shows inhibitory effects on angiotensinogen production in Cortisone (HY-17461)-treated 3T3-L1 adipocytes[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
JTT-654 (1-10 mg/kg, Orally, once daily for 4 d) significantly attenuates the effect of Cortisone (HY-17461) in Rats[1].
JTT-654 (1.5-15 mg/kg, Orally, twice daily, for 19 d) ameliorates insulin resistance and hyperglycemia in a non-obese type 2 diabetes rat model[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:SD rats (8 weeks old)[1]
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Dosage:1, 3, or 10 mg/kg
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Administration:Orally, single administration
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Result:The inhibitory effect for cortisone-cortisol conversion in liver and fat was dose dependent. In the 10 mg/kg JTT-654 group, the % inhibition in both tissues (Liver and Adipose) was almost 100% up to 8 h post-dose, and approximately 70% inhibition was still observed even at 24 h post-dose.
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Animal Model:Male Wistar rats (7-week-old)[1]
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Dosage:1, 3, 10 mg/kg
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Administration:Orally, once daily for 4 d, Cortisone was administered 1 h after JTT-654 administration on each day of dosing.
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Result:Significantly attenuated the increase in fasted plasma glucose and insulin levels in a dose-dependent manner.
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Animal Model:Non-obese type 2 diabetic Goto-Kakizaki (GK) Rats (8-week-old, male)[1]
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Dosage:1.5, 5, 15 mg/kg
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Administration:Orally, twice daily, for 19 d
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Result:Significantly reduced fasting plasma glucose and insulin levels, enhanced insulin-stimulated glucose oxidation in adipose tissue, and suppressed hepatic gluconeogenesis.
Ensayo clínico
| NCT Number | Sponsor | Condition | Start Date |
Phase
|
|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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No. CAS 916828-66-5
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Peso molecular 530.58
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Fòrmula C28H33F3N4O3
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SMILES
FC(F)(F)C1=CC=CC=C1[C@H]2CN(C(C3=C(C4CC4)N(C5CCN(C(C6(CC6)CO)=O)CC5)N=C3)=O)CC2
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
[1]. Heitaku S, et al. An 11-Beta Hydroxysteroid Dehydrogenase Type 1 Inhibitor, JTT-654 Ameliorates Insulin Resistance and Non-obese Type 2 Diabetes. Biol Pharm Bull. 2023;46(7):969-978. [Content Brief]
[2]. Heitaku S, et al. JTT-654, an 11-beta hydroxysteroid dehydrogenase type 1 inhibitor, improves hypertension and diabetic kidney injury by suppressing angiotensinogen production. J Pharmacol Sci. 2024 Apr;154(4):246-255. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
JTT-654 Related Classifications
HY-161449 Related Classifications
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