产品
编 号：F756062
分子式：C25H33ClN6O5
分子量：533.02
分子式：C25H33ClN6O5
分子量：533.02
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CAS No: 2803329-86-2
产品详情
生物活性：
JAK3-IN-13 is a potent, selective and orally active JAK3 inhibitor with IC50 values of 4728, 2039, 8, 365 nM for NK1, JNK2, JNK3, Tyk2, respectively. JAK3-IN-13 shows antiproliferative activity. JAK3-IN-13 induces cell cycle arrest at G0/G1 phase. JAK3-IN-13 shows antitumor activity.
体内研究：
JAK3-IN-13 (5 mg/kg for i.v.; 15 mg/kg for p.o.) shows good PK properties and oral bioavailability of 20.66%.JAK3-IN-13 (12.5, 25, 50 mg/kg; p.o.; twice daily for 10 days) shows antitumor activity and inhibits the expression of phosphorylation JAK3, STAT3, STAT5, CDK2, CDK4, CDK6, cyclin B1, cyclin D3, and cyclin E1.Pharmacokinetic Parameters of JAK3-IN-13 in Male Sprague-Dawley rats.12ni.v.(5 mg/kg) p.o.(15 mg/kg)
anminal no.33
T1/2 (h)0.910.98
Cmax (ng/mL)911.33238.28
AUC(0-∞) (h·ng/mL)536.99333.50
CL (mL/min/kg)155.22
F %20.66
Male Sprague-Dawley rats, 5 mg/kg iv (5% DMSO + 10% solutol + 85% saline); 15 mg/kg po (0.5% HPMC in water)Animal Model:Male Sprague-Dawley rats
Dosage:5 mg/kg for i.v.; 15 mg/kg for p.o.
Administration:I.v. or p.o.
Result:Showed good PK properties and oral bioavailability of 20.66%.
Animal Model:Male CB17-SCID mice (U937 mouse xenograft model)
Dosage:12.5, 25, 50 mg/kg
Administration:P.o.; twice daily for 10 days (10 mg/kg; i.p.; once daily)
Result:Dose-dependently inhibited the growth of the U937 tumor and significantly inhibited the expression of phosphorylation JAK3, STAT3, and STAT5 as well as the cell cycle-related proteins.
体外研究：
JAK3-IN-13 (compound 12n) (10 μM; 72 h) shows antiproliferative activity in BaF3-JAK3M511I, U937, parental cells.JAK3-IN-13 inhibits the activity of TEL-JNK1, TEL-JNK2, JNK3M511I, JNK3 with IC50 values of 177.7, 134.2, 22.9, 1.2 nM, respectively.JAK3-IN-13 inhibits (0-800 nM; 0-24 h) decreases the expression of phosphorylation JAK3, STAT3, and STAT5 in a dose-dependent manner.JAK3-IN-13 inhibits (0-330 nM; 24 h) induces cell cycle arrest at G0/G1 phase and down-regulates the expression of cyclin-dependent kinase 2 (CDK2), CDK4, CDK6, cyclin B1, cyclin D3, and cyclin E1 in a concentration-dependent manner.
JAK3-IN-13 is a potent, selective and orally active JAK3 inhibitor with IC50 values of 4728, 2039, 8, 365 nM for NK1, JNK2, JNK3, Tyk2, respectively. JAK3-IN-13 shows antiproliferative activity. JAK3-IN-13 induces cell cycle arrest at G0/G1 phase. JAK3-IN-13 shows antitumor activity.
体内研究：
JAK3-IN-13 (5 mg/kg for i.v.; 15 mg/kg for p.o.) shows good PK properties and oral bioavailability of 20.66%.JAK3-IN-13 (12.5, 25, 50 mg/kg; p.o.; twice daily for 10 days) shows antitumor activity and inhibits the expression of phosphorylation JAK3, STAT3, STAT5, CDK2, CDK4, CDK6, cyclin B1, cyclin D3, and cyclin E1.Pharmacokinetic Parameters of JAK3-IN-13 in Male Sprague-Dawley rats.12ni.v.(5 mg/kg) p.o.(15 mg/kg)
anminal no.33
T1/2 (h)0.910.98
Cmax (ng/mL)911.33238.28
AUC(0-∞) (h·ng/mL)536.99333.50
CL (mL/min/kg)155.22
F %20.66
Male Sprague-Dawley rats, 5 mg/kg iv (5% DMSO + 10% solutol + 85% saline); 15 mg/kg po (0.5% HPMC in water)Animal Model:Male Sprague-Dawley rats
Dosage:5 mg/kg for i.v.; 15 mg/kg for p.o.
Administration:I.v. or p.o.
Result:Showed good PK properties and oral bioavailability of 20.66%.
Animal Model:Male CB17-SCID mice (U937 mouse xenograft model)
Dosage:12.5, 25, 50 mg/kg
Administration:P.o.; twice daily for 10 days (10 mg/kg; i.p.; once daily)
Result:Dose-dependently inhibited the growth of the U937 tumor and significantly inhibited the expression of phosphorylation JAK3, STAT3, and STAT5 as well as the cell cycle-related proteins.
体外研究：
JAK3-IN-13 (compound 12n) (10 μM; 72 h) shows antiproliferative activity in BaF3-JAK3M511I, U937, parental cells.JAK3-IN-13 inhibits the activity of TEL-JNK1, TEL-JNK2, JNK3M511I, JNK3 with IC50 values of 177.7, 134.2, 22.9, 1.2 nM, respectively.JAK3-IN-13 inhibits (0-800 nM; 0-24 h) decreases the expression of phosphorylation JAK3, STAT3, and STAT5 in a dose-dependent manner.JAK3-IN-13 inhibits (0-330 nM; 24 h) induces cell cycle arrest at G0/G1 phase and down-regulates the expression of cyclin-dependent kinase 2 (CDK2), CDK4, CDK6, cyclin B1, cyclin D3, and cyclin E1 in a concentration-dependent manner.
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