PROTAC TTK degrader-2 是一种有效的TTK(苏氨酸酪氨酸激酶)PROTAC降解剂，在 COLO-205 和 HCT-116 细胞中的DC50值分别为 3.1 和 12.4 nM。PROTAC TTK degrader-2 在 COLO-205 人结直肠癌细胞异种移植小鼠模型中显示出靶向降解和抗癌效果。
| 生物活性 | PROTACTTK degrader-2 is a potentTTK(threonine tyrosine kinase)PROTACdegrader, withDC50values of 3.1 and 12.4 nM in COLO-205 and HCT-116 cell, respectively.PROTACTTK degrader-2 exhibits target degradation and anticancer efficacy in a xenograft mouse model of COLO-205 human colorectalcancercells[1]. |
| IC50& Target | DC50: 3.1 nM (TTK) in COLO-205, 12.4 nM (TTK) in HCT-116[1] |
体外研究
(In Vitro) | PROTAC TTK degrader-2 (compound 8j) (0-10 μM, 96 h) inhibits cancer cell proliferation[1].
PROTAC TTK degrader-2 (5 and 50 nM, 6 h) induces degradation ofTTKprotein in a dose-dependent manner[1].
Cell Proliferation Assay | Cell Line: | COLO-205 and HCT-116 cells[1] | | Concentration: | 0-10 μM | | Incubation Time: | 96 h | | Result: | Inhibited the growth of COLO-205 cancer cells with anIC50of 0.2 μM. |
Western Blot Analysis | Cell Line: | COLO-205, HCT-116 LOVO, HCT-8, and HCT-29 human colon cancer cell lines[1] | | Concentration: | 5, 50 nM | | Incubation Time: | 6 h | | Result: | Induced degradation ofTTKprotein in a dose-dependent manner. |
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体内研究
(In Vivo) | PROTAC TTK degrader-2 (8j) (10 mg/kg, IP, single) demonstrates reasonable pharmacokinetics profiles[1].
PROTAC TTK degrader-2 (10, 20 mg/kg, IP, once daily for 16 days) significantly reduces the TTK protein levels, and exhibits tumor-growth inhibition[1].
Pharmacokinetic Parameters of PROTAC TTK degrader-2 in male SD rats[1].
| 8j | | AUC (ng/mL*h) | 2333 | | T1/2(h) | 3.2 |
| Animal Model: | Male SD rats (, three animals per group)[1] | | Dosage: | 10 mg/kg, dissolved in mixed solvents (5% 20 mg/mL DMSO stock, 30% PG, 30% PEG400, and 35% Saline) | | Administration: | IP, single (Pharmacokinetic Analysis) | | Result: | Demonstrated reasonable pharmacokinetics profiles. |
| Animal Model: | Male CB17-SCID mice (xenograft mouse model of COLO-205 cells)[1] | | Dosage: | 10, 20 mg/kg | | Administration: | IP, once daily for 16 days | | Result: | Significantly reduced the TTK protein levels in animal tumor tissues, exhibited tumor-growth inhibition value of 36.7% upon 20 mg/kg dosing, did not cause a significant body weight loss of the animal. |
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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. |
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