| Size | Price | Stock | Qty |
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| 100mg |
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| 1g | |||
| Other Sizes |
| Targets |
The primary target of DDR-TRK-1 is Discoidin Domain Receptor 1 (DDR1), a receptor tyrosine kinase that belongs to the DDR family. DDR1 is activated by various types of collagen, particularly collagen types I-IV, and is involved in the regulation of cell adhesion, proliferation, migration, and extracellular matrix remodeling. Unlike other receptor tyrosine kinases, DDRs have a unique discoidin homology domain in their extracellular region that mediates collagen binding. DDR1 is frequently overexpressed in various cancers and fibrotic diseases, where it promotes tumor progression, invasion, and fibrosis. DDR-TRK-1 also inhibits the TRK kinase family (tropomyosin receptor kinases), which are involved in neuronal development and are implicated in certain cancers. The compound's dual inhibition of DDR1 and TRK kinases makes it a valuable tool for studying the roles of these kinases in disease.
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| ln Vitro |
DDR-TRK-1 is a potential contender, having an IC50 of 9.4 nM against DDR1. DDR-TRK-1 also has reasonable pharmacokinetic (PK) qualities, with an oral bioavailability of 66.8% and a T1/2 value of 1.25 hours at a dosage of 20 mg/kg in rats. DDR-TRK-1 had a greater AUC value in mice compared to rats, indicating effective absorption. The DDR1 inhibition of DDR1-IN-3 is further verified by evaluating its affinity for the DDR1 protein. DDR-TRK-1 is demonstrated to bind strongly to DDR1, with a binding constant (Kd) of 4.7 nM [1].
In vitro, DDR-TRK-1 demonstrates potent and selective inhibition of DDR1 with an IC₅₀ of 9.4 nM. It also inhibits the TRK kinase family. The compound effectively inhibits colony formation and migration of Panc-1 pancreatic cancer cells, indicating its potential to suppress tumor cell proliferation and invasiveness. In cellular models of lung fibrosis, DDR-TRK-1 inhibits signaling and expression of fibrotic markers and fibrotic features such as hydroxyproline expression. This suggests that the compound may have therapeutic potential in fibrotic diseases where DDR1 signaling drives pathological extracellular matrix deposition. The compound's high selectivity for DDR1 over other kinases is a key feature that minimizes off-target effects. The in vitro activity of DDR-TRK-1 supports its use as a chemical probe for studying DDR1 and TRK kinase biology. |
| ln Vivo |
In a dose-dependent way, DDR-TRK-1 averts these pathogenic alterations brought on by BLM. The expression levels of fibrotic markers, such as fibronectin and α-smooth muscle actin (SMA), in lung tissue lysates are consistent with our observations. Additional analyses also show that the delivery of DDR-TRK-1 suppresses the amount of hydroxyproline, a special amino acid present in collagen, in a dose-dependent manner. All of the aforementioned information points to the therapeutic potential of DDR-TRK-1 against pulmonary fibrosis caused by BLM[1].
In vivo, DDR-TRK-1 has demonstrated activity in mouse models of lung fibrosis, where it inhibits fibrotic features such as hydroxyproline expression. This indicates that the compound can effectively reach its target tissues and modulate DDR1-mediated fibrotic processes in a living organism. The compound's reasonable pharmacokinetic properties, including an oral bioavailability of 66.8% in rats and a half-life of 1.25 hours, support its use in in vivo studies. The ability to inhibit colony formation and migration of pancreatic cancer cells in vitro suggests potential antitumor activity that could be further evaluated in xenograft models. However, comprehensive in vivo efficacy studies in cancer models have not been extensively reported. The compound's dual inhibition of DDR1 and TRK kinases may provide additional therapeutic benefits in diseases where both pathways are implicated. |
| Enzyme Assay |
In vitro enzyme assays for DDR-TRK-1 typically measure its ability to inhibit the kinase activity of DDR1 and TRK family members. Kinase assays are performed using purified recombinant DDR1 or TRK kinases, a peptide substrate, and ATP. The transfer of phosphate from ATP to the substrate is measured using radioactive (³³P-ATP) or fluorescence-based methods. The assay is performed in the presence of varying concentrations of DDR-TRK-1, and IC₅₀ values are determined from dose-response curves. Selectivity profiling against a panel of kinases is conducted to confirm the compound's specificity for DDR1 and TRK kinases. Additionally, binding assays such as surface plasmon resonance (SPR) can be used to measure the compound's affinity for DDR1. These biochemical assays are essential for characterizing the compound's potency and selectivity.
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| Cell Assay |
In vitro cell-based assays for DDR-TRK-1 evaluate its effects on cellular functions such as proliferation, migration, and fibrotic marker expression. Panc-1 pancreatic cancer cells are commonly used to assess the compound's ability to inhibit colony formation and cell migration. For fibrosis studies, lung fibroblasts or other collagen-responsive cells are treated with DDR-TRK-1 in the presence or absence of collagen stimulation. Fibrotic markers such as α-SMA, collagen I, and fibronectin are measured by Western blot or qPCR. Hydroxyproline content, a measure of collagen deposition, can be quantified in cell culture supernatants or cell lysates. Cell viability assays (MTT or CellTiter-Glo) are performed to distinguish antiproliferative effects from cytotoxicity. These assays confirm the compound's mechanism of action and provide functional data on its cellular activity.
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| Animal Protocol |
In vivo animal studies for DDR-TRK-1 have been conducted in mouse models of lung fibrosis. In a typical study, lung fibrosis is induced by intratracheal administration of bleomycin or other fibrotic agents. Mice are then treated with DDR-TRK-1 via oral administration, given its favorable oral bioavailability. Endpoints include assessment of lung hydroxyproline content as a measure of collagen deposition, histological evaluation of lung fibrosis using Masson's trichrome staining, and measurement of fibrotic marker expression by immunohistochemistry or qPCR. For cancer studies, potential xenograft models using DDR1-expressing cancer cell lines could be employed, with endpoints including tumor growth inhibition and assessment of DDR1 signaling in tumor tissue. These studies are crucial for validating the compound's therapeutic potential in vivo.
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| ADME/Pharmacokinetics |
DDR-TRK-1 demonstrates reasonable pharmacokinetic properties, with an oral bioavailability of 66.8% in rats at a dose of 20 mg/kg and a half-life (T₁/₂) of 1.25 hours. This favorable oral bioavailability supports its use in in vivo studies via oral administration. The compound's molecular weight and chemical properties suggest it has drug-like characteristics suitable for systemic administration. Detailed pharmacokinetic parameters such as volume of distribution, clearance, and protein binding are not extensively reported in the publicly available literature. The compound's metabolic stability and potential for drug-drug interactions would need to be characterized in further studies. Its reasonable PK profile, combined with potent DDR1 inhibition, makes DDR-TRK-1 a promising tool compound for studying DDR1-related diseases in vivo.
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| Toxicity/Toxicokinetics |
Specific toxicity data for DDR-TRK-1 is not extensively reported in the publicly available literature. As a kinase inhibitor, its selectivity profile is a key determinant of its toxicity. The compound's high selectivity for DDR1 and TRK kinases over other kinases suggests a potentially favorable safety profile. However, comprehensive toxicology studies, including assessments of genotoxicity, acute and chronic toxicity, and effects on major organ systems, would be required before clinical development. The compound is currently classified as a research-grade chemical and is not intended for human use. Standard laboratory safety precautions should be followed when handling DDR-TRK-1. Any potential off-target effects related to TRK kinase inhibition, given the role of TRKs in neuronal development and function, would need to be carefully evaluated.
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| References | |
| Additional Infomation |
DDR-TRK-1 (compound 6j) is a potent and highly selective inhibitor of Discoidin Domain Receptor 1 (DDR1) with an IC₅₀ of 9.4 nM. It also inhibits the TRK kinase family, making it a dual inhibitor. The compound demonstrates reasonable pharmacokinetic properties, including 66.8% oral bioavailability in rats and a half-life of 1.25 hours. DDR-TRK-1 inhibits colony formation and migration of Panc-1 pancreatic cancer cells and shows efficacy in mouse models of lung fibrosis by reducing fibrotic markers and hydroxyproline expression. It is a valuable research tool for studying DDR1 and TRK kinase biology in cancer and fibrotic diseases. The compound has not received FDA approval for any indication and is intended for laboratory use only.
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| Molecular Formula |
C26H23F3N6O
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|---|---|
| Exact Mass |
492.188
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| CAS # |
1912357-12-0
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| PubChem CID |
121231414
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
4.1
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
36
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| Complexity |
763
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C[C@H]1CN(CC2=C1C=CC(=C2)C(=O)NC3=CC(=CC(=C3)C(F)(F)F)N4C=C(N=C4)C)C5=CN=CN=C5
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| InChi Key |
CMJJZRAAQMUAFH-INIZCTEOSA-N
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| InChi Code |
InChI=1S/C26H23F3N6O/c1-16-11-34(23-9-30-14-31-10-23)13-19-5-18(3-4-24(16)19)25(36)33-21-6-20(26(27,28)29)7-22(8-21)35-12-17(2)32-15-35/h3-10,12,14-16H,11,13H2,1-2H3,(H,33,36)/t16-/m0/s1
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| Chemical Name |
(4R)-4-methyl-N-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]-2-pyrimidin-5-yl-3,4-dihydro-1H-isoquinoline-7-carboxamide
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| Synonyms |
DDR-TRK1; DDRTRK-1; DDR-TRK-1
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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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