JAK3-IN-13 是一种有效、选择性和口服活性的JAK3抑制剂，对 NK1、JNK2、JNK3、Tyk2 的IC50值分别为 4728、2039、8、365 nM。JAK3-IN-13 显示出抗增殖活性。JAK3-IN-13诱导细胞周期停滞在 G0/G1 期。JAK3-IN-13 具有抗肿瘤活性。

JAK3-IN-13 is a potent, selective and orally active JAK3 inhibitor with IC 50 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 [1].

JAK3-IN-13 (compound 12n) (10 μM; 72 h) shows antiproliferative activity in BaF3-JAK3 M511I, U937, parental cells [1]. JAK3-IN-13 inhibits the activity of TEL-JNK1, TEL-JNK2, JNK3 M511I, JNK3 with IC 50 values of 177.7, 134.2, 22.9, 1.2 nM, respectively [1]. JAK3-IN-13 inhibits (0-800 nM; 0-24 h) decreases the expression of phosphorylation JAK3, STAT3, and STAT5 in a dose-dependent manner [1]. 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 [1]. Cell Proliferation Assay [1] Cell Line: BaF3-JAK3 M511I, U937, parental, COLO-205, H1299, HCT-116, MDA-MB-231, AGS, HL 7702 cells Concentration: 10 μM Incubation Time: 72 h Result: Showed antiproliferative activity with IC 50 s of 22.9, 20.2, 165.1 nM for BaF3-JAK3 M511I, U937, parental cells, and >10, >10, >10, >10, >10, 3.27 μM for COLO-205, H1299, HCT-116, MDA-MB-231, AGS, HL 7702 cells, respectively. Western Blot Analysis [1] Cell Line: U937 cells Concentration: 0-800 nM Incubation Time: 0-24 h Result: Dose-dependently suppressed the phosphorylation of JAK3, STAT3, and STAT5 and achieved near-complete inhibition at 200 nM. Cell Cycle Analysis [1] Cell Line: U937 cells Concentration: 0-330 nM Incubation Time: 24 h Result: Induced cell cycle arrest at G0/G1 phase and down-regulated 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 (5 mg/kg for i.v.; 15 mg/kg for p.o.) shows good PK properties and oral bioavailability of 20.66% [1]. 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 [1]. Pharmacokinetic Parameters of JAK3-IN-13 in Male Sprague-Dawley rats [1]. 12n i.v.(5 mg/kg) p.o.(15 mg/kg) anminal no. 3 3 T 1/2 (h) 0.91 0.98 C max (ng/mL) 911.33 238.28 AUC (0-∞) (h·ng/mL) 536.99 333.50 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) [1] Animal Model: Male Sprague-Dawley rats [1] 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) [1] 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.

C25H33ClN6O5

533.02

(< 1 mg/ml refers to the product slightly soluble or insoluble )
Powder: -20°C for 3 years
In solvent: -80°C for 2 years