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| Targets |
The primary targets of TYRA-200 are FGFR1, FGFR2, and FGFR3. FGFRs are receptor tyrosine kinases (RTKs) involved in cell proliferation, survival, and differentiation. Mutations or fusions in FGFR2 are common drivers of intrahepatic cholangiocarcinoma. TYRA-200 acts as an antagonist by binding to the ATP‑binding pocket of these kinases, inhibiting their autophosphorylation and blocking downstream signaling pathways (e.g., RAS/MAPK, PI3K/AKT, JAK/STAT). This leads to the inhibition of tumor cell growth and proliferation, particularly in tumors driven by FGFR2 alterations.
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| ln Vitro |
In vitro, TYRA-200 is an orally active FGFR1/2/3 inhibitor. The specific IC₅0 values for FGFR1, FGFR2, and FGFR3 are not listed in the provided sources. The compound's activity is being studied in FGFR2-driven tumors, including both wild‑type and mutant FGFR2 models. It is highly selective, targeting FGFR1/2/3. It shows efficacy in cell viability assays using cancer cell lines with FGFR genetic alterations.
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| ln Vivo |
In vivo, TYRA-200 shows dose‑dependent tumor regression in both wild‑type FGFR2 and FGFR2 mutant mice models. In these animal models, oral administration of TYRA-200 leads to a significant reduction in tumor volume, indicating robust antitumor activity. The compound is being developed for the treatment of advanced or metastatic intrahepatic cholangiocarcinoma (IHCC) and other FGFR2‑driven solid tumors.
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| Enzyme Assay |
Non-cell-based (cell-free) experiments for TYRA-200 are used to determine its potency and selectivity against FGFR kinases. A standard protocol uses recombinant, active FGFR1, FGFR2, and FGFR3 enzymes in a kinase assay. The enzyme is incubated with a specific peptide substrate (e.g., a biotinylated substrate) and ATP in the presence of increasing concentrations of TYRA-200 (0.001-10 uM). The reaction proceeds for 30-60 minutes at room temperature. The phosphorylated substrate is detected using a homogeneous time-resolved fluorescence (HTRF) or AlphaScreen detection system. The IC₅0 values for each FGFR are calculated from dose-response curves. The selectivity is assessed by testing the compound against a panel of 50-100 other kinases.
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| Cell Assay |
Cell-based assays for TYRA-200 are conducted in cancer cell lines driven by FGFR2 alterations. Cells (e.g., SNU-16, KATO III gastric cancer cells with FGFR2 amplifications, or NIH3T3 cells transformed with FGFR2 fusions) are seeded in 96‑well plates. After overnight attachment, cells are treated with increasing concentrations of TYRA-200 (0.1-1000 nM) for 72 hours. Cell viability is measured by the CellTiter‑Glo (CTG) or MTT assay. The half‑maximal inhibitory concentration (IC₅0) is calculated. To confirm target engagement, cells are treated with the compound for 2-4 hours, and cell lysates are analyzed by Western blotting for phospho‑FGFR (p‑FGFR), phospho‑ERK (p‑ERK), and phospho‑AKT (p‑AKT).
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| Animal Protocol |
In vivo animal experiments for TYRA-200 are conducted in mouse xenograft models using human cancer cells harboring FGFR2 alterations. Nude mice are implanted subcutaneously with FGFR2‑driven tumor cells (e.g., SNU-16 or a patient‑derived xenograft (PDX) model of IHCC). When tumors reach a certain size (e.g., 150-200 mm3), mice are randomized to treatment groups. TYRA-200 is administered orally at doses of 1-100 mg/kg once or twice daily for 2-4 weeks. Tumor volume is measured by calipers twice weekly. Body weight is monitored as a general indicator of toxicity. At the end of the study, tumors are excised and weighed. Tumor tissue is analyzed for markers of FGFR pathway inhibition (p‑FGFR, p‑ERK, p‑AKT) by immunohistochemistry (IHC) or Western blotting. TYRA-200 shows dose‑dependent tumor regression in both wild‑type FGFR2 and FGFR2 mutant mice models.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for TYRA-200 are limited in the provided sources. The compound has a molecular formula of C23H24FN₇O2 and a molecular weight of 449.48 g/mol. As an orally active compound, it has good oral bioavailability and metabolic stability. The compound is a solid at room temperature and is stored at -20degC, protected from light. It is soluble in DMSO and organic solvents.
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| Toxicity/Toxicokinetics |
The toxicity of TYRA-200 has not been fully characterized. In the provided material, it is labeled as a hazardous ingredient and is described as "Toxic". Off‑target inhibition of FGFRs can cause hyperphosphatemia, retinal detachment, and nail changes. As a research chemical, standard safety precautions apply: the compound may be harmful if swallowed, inhaled, or absorbed through the skin. It may cause skin and eye irritation. It should be handled in a well-ventilated area (fume hood) with appropriate PPE (lab coat, gloves, safety goggles). The product is not for human or veterinary use.
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| References |
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| Additional Infomation |
Additional information: The compound has a CAS number of 2823289-77-4. It is also known as TYRA-200 and is an FGFR1/2/3 inhibitor. It is for research use only and is not for diagnostic or therapeutic use in humans. Synonyms include TYRA-200 and FGFR1/2/3 antagonist.
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| Molecular Formula |
C23H24FN7O2
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| Molecular Weight |
449.48
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| CAS # |
2823289-77-4
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| Appearance |
Off-white to light yellow 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 |
| 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 (~222.48 mM; with sonication)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (11.12 mM)(saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one)),clear solution.
For example, if 1 mL of working solution is to be prepared, you can Add 100 μL of 50.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix thoroughly. Then add 50 μL of Tween-80 to the above system and mix thoroughly. Finally, add 450 μL of physiological saline to bring the volume to 1 mL. Preparation of physiological saline: Dissolve 0.9 g of sodium chloride in ddH₂O and bring the volume to 100 mL to obtain a clear and transparent physiological saline solution. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 5 mg/mL (11.12 mM)(saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one)),clear solution. For example, if 1 mL of working solution is to be prepared, you can Add 100 μL of 50.0 mg/mL clarified DMSO stock solution to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2248 mL | 11.1240 mL | 22.2479 mL | |
| 5 mM | 0.4450 mL | 2.2248 mL | 4.4496 mL | |
| 10 mM | 0.2225 mL | 1.1124 mL | 2.2248 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
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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