TP-5801

TP-5801 is an orally active TNK1 (non-receptor tyrosine kinase) inhibitor (IC50=1.40 nM), and shows anti-tumor activity[1].

Research Areas >> Cancer

Signaling Pathways >> Others >> Others

IC50: 1.40 nM (TNK1)[1]

TP-5801 (10 pM-10 mM; 72 h) treatment inhibits TNK1-driven, BCR-ABL-driven and IL-3-driven Ba/F3 cell growth[1]. TP-5801 (1 nM-10 μM; 10 d) inhibits TNK1-dependent L540 cell growth[1]. Cell Viability Assay[1] Cell Line: Ba/F3 cells Concentration: 10 pM -10 mM 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) treatment shows efficacy in the mouse survival model[1]. TP-5801 (oral gavage; 50 mg/kg; once daily; 7 d) treatment can inhibit localized tumor growth[1]. Animal Model: Female NOD/SCID mice injected with Ba/F3 luc 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 luc 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.