| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Targets |
IC50: 1.40 nM (TNK1)[1]
TP-5801 TFA specifically targets TNK1 (non-receptor tyrosine kinase), an understudied kinase that has been implicated in various cancers. TNK1 is part of the JAK/STAT signaling pathway. By inhibiting TNK1, TP-5801 suppresses the phosphorylation of STAT proteins and subsequently downstream gene expression. The IC50 of 1.40 nM indicates extremely high potency against this target. The compound is also an effective inhibitor in cells, showing robust activity in TNK1-driven, BCR-ABL-driven, and IL-3-driven cellular models, indicating that its mechanism of action involves the disruption of multiple oncogenic signaling pathways. |
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| ln Vitro |
Treatment with TP-5801 (10 pM-10 μM; 72 h) TFA reduces the development of Ba/F3 cells stimulated by TNK1, BCR-ABL, and IL-3 [1]. TNK1-dependent L540 cell proliferation is inhibited by TP-5801 (1 nM-10 μM; 10 d) TFA [1].
In vitro studies show that TP-5801 TFA is a highly effective cell growth inhibitor in various cancer cell lines. At concentrations ranging from 10 pM to 10 microM, treatment with TP-5801 for 72 hours is able to suppress the development of Ba/F3 cells driven by TNK1, BCR-ABL, and IL-3. Specifically, it inhibits the growth of WT TNK1 and AAA mutant cells with IC50 values of 76.78 nM and 36.95 nM, respectively. Furthermore, it inhibits BCR-ABL-driven and IL-3-driven Ba/F3 cell growth with IC50 values of 8.5 and 1.2 microM, respectively [30L16-L24]. In addition, a 10-day treatment with TP-5801 TFA at 1-1000 nM is sufficient to inhibit the growth of TNK1-dependent L540 lymphoma cells at low nM levels [30L17-L18][30L25-L26]. |
| ln Vivo |
TP-5801 (10 mg/kg; oral gavage, once) In a mouse tumor survival model, TFA is beneficial [1]. TP-5801 (oral gavage, once day, 50 mg/kg; 7 days) TFA can stop the growth of localized tumors [1].
In vivo studies confirm the oral activity and anti-tumor efficacy of TP-5801 TFA. In a mouse tumor survival model, a single oral dose of TP-5801 (10 mg/kg) was effective in increasing survival. Furthermore, in a localized tumor growth model, TP-5801 (oral gavage; 50 mg/kg; once daily; 7 days) was able to significantly suppress tumor growth [30L27-L28]. These results highlight the strong potential of TP-5801 as a therapeutic agent and validate TNK1 as an actionable target for cancer therapy. |
| Enzyme Assay |
For a cell-free binding (kinase inhibition) assay, a standard protocol can be used. Recombinant active TNK1 kinase is incubated with a peptide substrate, ATP, and varying concentrations of TP-5801 TFA (e.g., 0.001-10000 nM). The reaction is performed in a buffer containing 50 mM HEPES (pH 7.5), 10 mM MgCl2, 2 mM DTT, and 0.01% Brij-35. After incubation, the reaction is terminated by the addition of EDTA. The level of phosphorylated peptide substrate is then detected using a luminescence-based method (e.g., ADP-Glo™ Kinase Assay). The IC50 is calculated by fitting the inhibition curve to a four-parameter logistic model, yielding the reported 1.40 nM.
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: Ba/F3 cells Tested Concentrations: 10 pM-10 μM Incubation Duration: 72 hrs (hours) Experimental Results: 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 Types: L540 cells Tested Concentrations: 1, 10, 100, and 1000 nM Incubation Duration: 10 days Experimental Results: Inhibited TNK1-dependent L540 cell growth at low nM level. For in vitro cellular activity assays, the effect of TP-5801 TFA on cell proliferation can be measured using a cell viability assay. Ba/F3 or L540 cells (1 x 10^4 cells/well) are seeded into 96-well plates. Cells are then treated with TP-5801 TFA at concentrations ranging from 10 pM to 10 microM in triplicate for 72 hours. At the end of the incubation, 10 microL of Cell Counting Kit-8 (CCK-8) solution is added to each well and incubated for 2-4 hours. The absorbance is measured at 450 nm using a microplate reader. The half-maximal inhibitory concentration (IC50) for cell growth is calculated from the dose-response curve [30L19-L24]. |
| Animal Protocol |
Animal/Disease Models: Female NOD/SCID (severe combined immunodeficient) mouse injected with Ba/F3 luciferase cells expressing TNK1 AAA[1]
Doses: 10 mg/kg Route of Administration: po (oral gavage); 10 mg/kg; once Experimental Results: demonstrated no signs of toxicity and Dramatically prolonged lifespan. Animal/Disease Models: NOD/SCID (severe combined immunodeficient) mouse implanted subcutaneously (sc) with Ba/F3 luciferase cells expressing TNK1 AAA or BCR-ABL[1] Doses: 50 mg/kg Route of Administration: po (oral gavage); 50 mg/kg; one time/day; 7 days Experimental Results: decreased phospho -STAT3 in TNK1-driven xenografts at 2 hrs (hours) post-treatment, and tumor burden in mice xenografted. In vivo animal studies are typically conducted in mice. For a tumor xenograft model, Ba/F3 cells expressing TNK1 mutants are injected subcutaneously into female NOD/SCID mice. When the tumors reach an average volume of 100-200 mm3, the mice are randomized into treatment groups (n=5-10). TP-5801 TFA is administered orally at 10 mg/kg once or at 50 mg/kg once daily for 7 days. Tumor volumes and body weights are measured every 2-3 days. At the end of the study, plasma and tumors are collected for pharmacokinetic (PK) and pharmacodynamic (PD) analysis to measure compound levels and inhibition of downstream signaling (e.g., p-STAT levels by western blot), respectively [30L29-L31]. |
| ADME/Pharmacokinetics |
TP-5801 TFA is an orally active compound, implying it has good absorption from the gastrointestinal tract. Its calculated LogP is 4.3, and its topological polar surface area (tPSA) is 81.7, which is within the range for good oral absorption and cell permeability. Pharmacokinetic data from in vivo models show that a single oral dose of 10 mg/kg is sufficient to achieve therapeutic levels in mice, leading to increased survival in a tumor model. The compound is typically formulated for oral administration in vehicles such as 0.5% CMC-Na (carboxymethylcellulose sodium) or other standard oral formulations.
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| Toxicity/Toxicokinetics |
Formal toxicity data for TP-5801 TFA is not publicly available. As a research compound, standard safety precautions should be taken. The compound is not intended for human use, and its safety for human consumption has not been established. In animal efficacy studies, the compound was well-tolerated at the doses used (e.g., 10-50 mg/kg), with no obvious clinical signs of toxicity reported. However, complete toxicological profiling (e.g., acute, sub-chronic, chronic, and genotoxicity studies) would be required to assess its full safety profile. It is strictly for research use only.
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| References | |
| Additional Infomation |
TP-5801 TFA is a research-grade, potent, and selective inhibitor of the non-receptor tyrosine kinase TNK1 (Thirty-eight-negative kinase 1) and is used as a chemical probe to study TNK1 function in cancer biology. It has demonstrated robust anti-tumor activity in preclinical models of TNK1-driven malignancies and is valuable for investigating the role of TNK1 in cancer and other diseases. The compound is not approved for clinical use, is not in clinical trials, and is strictly intended for laboratory research use. The TFA salt form is used to enhance solubility and stability. It is typically stored at -20degC or 4degC, protected from light and moisture, for long-term stability [30L5-L6].
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| Molecular Formula |
C26H32BRF3N8O3
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| Related CAS # |
TP-5801;2574474-81-8
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| Appearance |
Light yellow to yellow solid powder
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO :~100 mg/mL (~155.89 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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