TP-5801 TFA 是一种具有口服活性的非受体酪氨酸激酶 (TNK1) 抑制剂 (IC50=1.40 nM)，并表现出抗肿瘤活性。
IC50: 1.40 nM (TNK1)[1]
TP-5801 TFA is an orally active TNK1 (non-receptor tyrosine kinase) inhibitor (IC50=1.40 nM), and shows anti-tumor activity[1].
TP-5801 (10 pM-10 μM; 72 h) TFA 处理抑制 TNK1 驱动、BCR-ABL 驱动和 IL-3 驱动的 Ba/F3 细胞生长[1]。
TP-5801 (1 nM-10 μM; 10 d) TFA 抑制 TNK1 依赖性 L540 细胞生长[1]。
Cell Viability Assay[1]
| Cell Line: | Ba/F3 cells |
| Concentration: | 10 pM-10 μM |
| Incubation Time: | 72 hours |
| Result: | Inhibited TNK1-driven cell growth with IC50s of 76.78 and 36.95 nM against WT TNK1 and AAA mutant cells, respectively. Inhibited BCR-ABL-driven and IL-3-driven Ba/F3 cell growth with IC50s of 8.5 and 1.2 μM, respectively. |
Cell Viability Assay[1]
| Cell Line: | L540 cells |
| Concentration: | 1, 10, 100, and 1000 nM |
| Incubation Time: | 10 days |
| Result: | Inhibited TNK1-dependent L540 cell growth at low nM level. |
TP-5801 (oral gavage; 10 mg/kg; once) TFA 在小鼠肿瘤存活模型中有效果[1]。
TP-5801 (oral gavage; 50 mg/kg; once daily; 7 d) TFA 可抑制局部肿瘤生长[1]。
| Animal Model: | Female NOD/SCID mice injected with Ba/F3 luciferase cells expressing TNK1 AAA[1] |
| Dosage: | 10 mg/kg |
| Administration: | Oral gavage; 10 mg/kg; once |
| Result: | Showed no signs of toxicity and significantly prolonged lifespan. |
| Animal Model: | NOD/SCID mice implanted subcutaneously with Ba/F3 luciferase cells expressing TNK1 AAA or BCR-ABL[1] |
| Dosage: | 50 mg/kg |
| Administration: | Oral gavage; 50 mg/kg; once daily; 7 days |
| Result: | Reduced phospho-STAT3 in TNK1-driven xenografts at 2 hours post-treatment, and tumor burden in mice xenografted. |
[1]. Tsz-Yin Chan, et al. TNK1 is a ubiquitin-binding and 14-3-3-regulated kinase that can be targeted to block tumor growth. Nat Commun. 2021 Sep 9;12(1):5337.
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