产品
编 号：F750329
分子式：C24H20F2N4O2
分子量：434.44
分子式：C24H20F2N4O2
分子量：434.44
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CAS No: 2244061-66-1
产品详情
生物活性：
TYK2-IN-12 (compound 30) is an orally active, potent and selective TYK2 (tyrosine kinase 2) inhibitor, with a Ki of 0.51 nM. TYK2-IN-12 inhibits IL-12 induced IFNγ, with IC50 values of 2.7 and 7.0 μM in human and mouse whole blood, respectively. TYK2-IN-12 can be used for psoriasis research.
体内研究：
TYK2-IN-12 (compound 30) (0-100 mg/kg, PO, daily for 10 days) dose-dependently reduces immune responses.TYK2-IN-12 (3 mg/kg (IV), 10 mg/kg (PO), once) shows moderate clearance and volumes of distribution, and exhibits moderate to good oral absorption.Pharmacokinetic Parameters of TYK2-IN-12 in male C57Bl/6 mice and smale Sprague-Dawley rats.SpeciesMouse Rat
PPB Fumax (h)0.0610.10
CL (mL/min/kg)2827
t1/2 (h)1.81.6
Vd (L/kg)1.21.9
F (%)>9032
Animal Model:C57BL/6 mice (IL-23 induced inflammation model)
Dosage:0, 10, 30, and 100 mg/kg
Administration:PO, daily for 10 days
Result:Dose-dependently reduced immune responses, with up to 74 % inhibition of ear swelling and 96 % inhibition of tissue levels of IL-17A at 100 mg/kg, highlighting the crucial role of TYK2 in IL-23 induced IL-17 and tissue inflammation. Exhibited improved skin histology and a dose-dependent reduction of spleen weight.
Animal Model:Male C57Bl/6 mice, male SD rats
Dosage:3 mg/kg (IV), 10 mg/kg (PO)
Administration:IV or PO, once (Pharmacokinetic Analysis)
Result:Showed moderate clearance and volumes of distribution of 1.2 L/Kg and 1.9 L/Kg, respectively in mouse and rat IV PK, and exhibited moderate to good oral absorption, with oral bioavailabilities of 32-100%.
体外研究：
TYK2-IN-12 (compound 30) shows 90, 43, and 13-fold selectivity over JAK1, JAK2, and JAK3, respectively.TYK2-IN-12 exhibits excellent selectivity over hERG (IC50 > 30 μM) and over a panel of 10 cytochrome P450 enzymes (IC50s > 30 μM against CYP450s 3A4, 3D6, 2C9, 2C8, 1A2, 2A6, 2B6, 2C19, 2E1, and 3A5).TYK2-IN-12 shows cell-based potency and selectivity in human PBMC by blockade of IL-12 induced phospho-STAT4, GM-CSF induced phospho-STAT5, and IL-2 induced phospho-STAT5, with IC50 values of 0.10 μM, 4.1 μM and 0.25 μM, respectively.
TYK2-IN-12 (compound 30) is an orally active, potent and selective TYK2 (tyrosine kinase 2) inhibitor, with a Ki of 0.51 nM. TYK2-IN-12 inhibits IL-12 induced IFNγ, with IC50 values of 2.7 and 7.0 μM in human and mouse whole blood, respectively. TYK2-IN-12 can be used for psoriasis research.
体内研究：
TYK2-IN-12 (compound 30) (0-100 mg/kg, PO, daily for 10 days) dose-dependently reduces immune responses.TYK2-IN-12 (3 mg/kg (IV), 10 mg/kg (PO), once) shows moderate clearance and volumes of distribution, and exhibits moderate to good oral absorption.Pharmacokinetic Parameters of TYK2-IN-12 in male C57Bl/6 mice and smale Sprague-Dawley rats.SpeciesMouse Rat
PPB Fumax (h)0.0610.10
CL (mL/min/kg)2827
t1/2 (h)1.81.6
Vd (L/kg)1.21.9
F (%)>9032
Animal Model:C57BL/6 mice (IL-23 induced inflammation model)
Dosage:0, 10, 30, and 100 mg/kg
Administration:PO, daily for 10 days
Result:Dose-dependently reduced immune responses, with up to 74 % inhibition of ear swelling and 96 % inhibition of tissue levels of IL-17A at 100 mg/kg, highlighting the crucial role of TYK2 in IL-23 induced IL-17 and tissue inflammation. Exhibited improved skin histology and a dose-dependent reduction of spleen weight.
Animal Model:Male C57Bl/6 mice, male SD rats
Dosage:3 mg/kg (IV), 10 mg/kg (PO)
Administration:IV or PO, once (Pharmacokinetic Analysis)
Result:Showed moderate clearance and volumes of distribution of 1.2 L/Kg and 1.9 L/Kg, respectively in mouse and rat IV PK, and exhibited moderate to good oral absorption, with oral bioavailabilities of 32-100%.
体外研究：
TYK2-IN-12 (compound 30) shows 90, 43, and 13-fold selectivity over JAK1, JAK2, and JAK3, respectively.TYK2-IN-12 exhibits excellent selectivity over hERG (IC50 > 30 μM) and over a panel of 10 cytochrome P450 enzymes (IC50s > 30 μM against CYP450s 3A4, 3D6, 2C9, 2C8, 1A2, 2A6, 2B6, 2C19, 2E1, and 3A5).TYK2-IN-12 shows cell-based potency and selectivity in human PBMC by blockade of IL-12 induced phospho-STAT4, GM-CSF induced phospho-STAT5, and IL-2 induced phospho-STAT5, with IC50 values of 0.10 μM, 4.1 μM and 0.25 μM, respectively.
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