BTK-IN-15 是一种新型的布鲁顿酪氨酸激酶 (BTK) 抑制剂，具有良好口服活性。BTK-IN-15 抑制BTK，IC50为 0.7 nM，并具有良好的激酶选择性和抗肿瘤活性，能诱导癌细胞凋亡 (apoptosis)。
| 生物活性 | BTK-IN-15 is a potentBruton's tyrosine kinase(BTK) inhibitor with highoralabsorption. BTK-IN-15 inhibitsBTKwith anIC50value of 0.7 nM. BTK-IN-15 displays excellent kinase selectivity, antitumor activity, and inducesapoptosis[1]. |
| IC50& Target | |
体外研究
(In Vitro) | BTK inhibition is an effective approach against B-cell malignancies[1].
BTK-IN-15 (compound 42) demonstrates inhibitory against TMD8 with an IC50value of 2.6 nM[1].
BTK-IN-15 (1 μM; 1 h) displays significant selectivity to BTK over EGFR kinase with 0.05% and 44% of the control, respectively[1].
BTK-IN-15 (0-1 mM; 72 h) exerts potent anti-proliferative activity against a human mantle cell lymphoma cell line (REC-1) with an IC50value of 1.7 nM[1].
BTK-IN-15 (0-1 mM; 2 h) inhibits BTK auto-phosphorylation with an IC50value of 1.49 nM[1].
BTK-IN-15 (0-100 nM; 48 h) arrests cell cycle at G1 phase and (0-1 mM; 72 h) induces apoptosis in TMD8[1].
BTK-IN-15 shows low hERG channel activity (IC50=4.38 μM), indicating low cardiotoxicity[1].
Western Blot Analysis[1] | Cell Line: | B-cell lymphoma (DLBCL) TMD8 cancer cells | | Concentration: | 0, 0.15, 0.46, 1.37, 4.12, 12.35, 37.04, 111, 333, 1000 nM | | Incubation Time: | 2 hours | | Result: | Inhibited BTK auto-phosphorylation at the Tyr223 site with an IC50value of 1.49 nM. |
Cell Cycle Analysis[1] | Cell Line: | B-cell lymphoma (DLBCL) TMD8 cancer cells | | Concentration: | 0, 10, 100 nM | | Incubation Time: | 48 hours | | Result: | Arrested cell cycle progression at G1 phase in a dose-dependent manner, the percentage of cells in the G0/G1 phase increased from 33.0 to 63.0% with a dose range of 1-100 nM. |
Apoptosis Analysis[1] | Cell Line: | B-cell lymphoma (DLBCL) TMD8 cancer cells | | Concentration: | 0, 10, 100, 1000 nM | | Incubation Time: | 72 hours | | Result: | Induced apoptosis of TMD8 cells in a weakly triggered concentration-dependent manner, with the apoptosis cell values of 19% (10 nM), 25.2% (100 nM), and 31.4% (1000 nM), respectively. |
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体内研究
(In Vivo) | BTK-IN-15 (compound 42) (12.5-50 mg/kg; p.o.; twice daily; 21 d) inhibits tumor growth (TGI = 104%) at a dosage of 50 mg/kg in mice[1].
BTK-IN-15 (300, 400, 500 mg/kg; p.o.; twice daily; 14 d) has biological safety and displays no affect against body weight in mice compared with control[1].
BTK-IN-15 (10 mg/kg; p.o.) shows a high oral bioavailability of 40.98% in mice[1].
Pharmacokinetics of BTK-IN-15 in Mice[1]
| Route | Dose (mg/kg) | Tmax(h) | Cmax(ng/mL) | AUC(0-t)(hong/mL) | AUC(0-∞)(hong/mL) | T1/2(h) | Vz(L/kg) | CL (L/h/kg) | F (%) | | i.v. | 2 | 0.03 | 2245.39 | 1471.35 | 718.33 | 0.67 | 2.79 | 2.87 | 40.98 | | p.o. | 10 | 0.39 | 1441.59 | 718.33 | 1472.06 | 0.59 | | | |
| Animal Model: | Female CB-17 SCID nude mice with TMD8 xenograft model[1] | | Dosage: | 12.5 mg/kg, 25 mg/kg, and 50 mg/kg | | Administration: | Oral gavage; twice daily; 21 days | | Result: | Inhibited tumor growth at a dosage of 50 mg/kg and reduced tumor volume after 21 days with a TGI of 104%.
Reduced the content of white blood cells, lymphocytes and monocytes, while showed no effect on red blood cell and platelets. |
| Animal Model: | ICR mice (acclimation for 5 days, 18-20 g)[1] | | Dosage: | 300, 400, 500 mg/kg | | Administration: | Oral gavage; 14 days | | Result: | Demonstrated no affect against body weight in mice compared with control. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
