| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
TrkA 99 nM (IC50) TrkB 81 μM (IC50) TrkC 25 μM (IC50)
TrkA (tropomyosin receptor kinase A). TrkA-IN-1 is a selective TrkA inhibitor, with an IC50 of 99 nM in a cell-based assay. It has reduced potency against other family members, TrkB (IC50 = 81 microM) and TrkC (IC50 = 25 microM). |
|---|---|
| ln Vitro |
TrkA-IN-1 potently inhibits TrkA in a cell-based assay, which measures the inhibition of NGF-stimulated TrkA phosphorylation. This selectivity for TrkA over TrkB and TrkC is critical for pain research, as it allows for the dissection of TrkA-specific pathways without off-target effects on the other Trk receptors, which are involved in neuronal survival and development.
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| ln Vivo |
TrkA-IN-1 has demonstrated analgesic activity in preclinical models of pain. By inhibiting TrkA, it blocks the NGF signaling cascade. NGF is a well-established mediator of pain and inflammation, and its inhibition is a validated strategy for treating chronic pain conditions. This makes TrkA-IN-1 a valuable tool for pain research.
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| Enzyme Assay |
Cell-free binding assays are performed using recombinant human TrkA enzyme. The enzyme is incubated with a substrate (e.g., poly(Glu,Tyr) peptide) and ATP. The compound is added, and kinase activity is measured by a homogeneous time-resolved fluorescence (HTRF) method. The IC50 is calculated from a dose-response curve.
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| Cell Assay |
Cell-based TrkA inhibition assays are performed using a human neuroblastoma cell line (e.g., SH-SY5Y) that expresses TrkA. Cells are treated with a range of TrkA-IN-1 concentrations before being stimulated with NGF. The level of phosphorylated TrkA (p-TrkA) in the cell lysates is measured by a sandwich ELISA using a phospho-specific antibody.
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| Animal Protocol |
To assess analgesic activity, a rodent model of NGF-induced hyperalgesia is used. Rats are injected intraplantarly with NGF to induce a localized pain response. TrkA-IN-1 is administered orally or intraperitoneally. Mechanical allodynia is then measured using von Frey filaments to determine the compound's effect on reversing NGF-induced pain behavior.
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| ADME/Pharmacokinetics |
No specific PK data are reported. The molecular weight is 392.45 (C25H20N4O), and the CAS number is 1680179-43-4. It is soluble in DMSO. For in vivo studies, the compound is typically formulated in a mixture of 10% DMSO, 40% PEG300, 5% Tween-80, and 45% saline to achieve a clear solution for injection.
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| Toxicity/Toxicokinetics |
No specific toxicity data are reported. As a TrkA inhibitor, the primary toxicity risk in a research context is on-target. While TrkA is a target for pain, it also plays a role in the nervous system. The compound is a research chemical and not for human use. It is not an approved drug.
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| References | |
| Additional Infomation |
Other information: TrkA-IN-1 is a chemical probe for studying the function of TrkA in pain and inflammation. Its selectivity over TrkB and TrkC is a key differentiator. It is a valuable tool for validating TrkA as a therapeutic target in drug discovery for chronic pain conditions like osteoarthritis and lower back pain.
|
| Molecular Formula |
C25H20N4O
|
|---|---|
| Molecular Weight |
392.4525
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| Exact Mass |
392.163
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| CAS # |
1680179-43-4
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| PubChem CID |
117967296
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| Appearance |
White to yellow solid powder
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| LogP |
4.2
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
30
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| Complexity |
570
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(N([H])C1=C([H])N=C(C([H])([H])[H])N=C1C1C([H])=C([H])C([H])=C([H])C=1[H])N([H])C1([H])C2=C([H])C([H])=C([H])C([H])=C2C2=C([H])C([H])=C([H])C([H])=C12
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| InChi Key |
PKOROKYRNIDSPX-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H20N4O/c1-16-26-15-22(23(27-16)17-9-3-2-4-10-17)28-25(30)29-24-20-13-7-5-11-18(20)19-12-6-8-14-21(19)24/h2-15,24H,1H3,(H2,28,29,30)
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| Chemical Name |
1-(9H-fluoren-9-yl)-3-(2-methyl-4-phenylpyrimidin-5-yl)urea
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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: 8.33 mg/mL (21.23 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 1 mg/mL (2.55 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1 mg/mL (2.55 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 10.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5481 mL | 12.7405 mL | 25.4810 mL | |
| 5 mM | 0.5096 mL | 2.5481 mL | 5.0962 mL | |
| 10 mM | 0.2548 mL | 1.2740 mL | 2.5481 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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