| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| Targets |
TP-0427736 HCl targets ALK5 (activin receptor-like kinase 5), also known as TGF-β type I receptor (TGF-βRI), a membrane-bound serine/threonine kinase. ALK5 is a key component of the TGF-β signaling pathway, which regulates cell growth, differentiation, apoptosis, and immune responses. By inhibiting ALK5 kinase activity with high potency (IC50 = 2.72 nM), TP-0427736 HCl blocks TGF-β-induced Smad2/3 phosphorylation and downstream signaling.
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| ln Vitro |
TP-0427736 HCl is a potent ALK5 kinase inhibitor with an IC50 of 2.72 nM, showing 300-fold selectivity over ALK3 (IC50 = 836 nM). It inhibits TGF-β1-induced Smad2/3 phosphorylation in A549 cells with an IC50 of 8.68 nM. The compound reduces TGF-β-induced growth inhibition in human outer root sheath cells and prolongs the hair follicle growth phase in mice. It is used in research on fibrosis, cancer, and other TGF-β-related diseases.
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| ln Vivo |
In vivo, TP-0427736 HCl prolongs the hair follicle growth phase (anagen) in mice. As a potent ALK5 inhibitor, it is expected to exhibit anti-fibrotic, anti-tumor, and immunomodulatory effects in vivo by blocking TGF-β signaling. Specific in vivo efficacy data and detailed animal model studies for other indications are not extensively documented. The compound is intended for research use only.
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| Enzyme Assay |
The in vitro kinase assay for TP-0427736 HCl typically involves measuring the inhibition of ALK5 kinase activity. Recombinant ALK5 kinase is incubated with varying concentrations of TP-0427736 HCl (typically 0.001-100 µM) in the presence of ATP and a peptide substrate. The kinase activity is measured by monitoring the phosphorylation of the substrate using radiometric (33P-ATP) or fluorescence-based detection methods. The IC50 value (2.72 nM) is determined by plotting the percentage of inhibition against compound concentration.
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| Cell Assay |
In vitro cellular assays for TP-0427736 HCl typically involve treating A549 cells or other TGF-β-responsive cell lines with the compound at concentrations ranging from 0.001 to 10 µM for 1-24 hours. Cells are stimulated with TGF-β1, and Smad2/3 phosphorylation is assessed by Western blot. The IC50 for inhibition of Smad2/3 phosphorylation (8.68 nM) is determined. Cell viability and proliferation are assessed using standard assays. The compound is dissolved in DMSO and diluted in cell culture medium.
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| Animal Protocol |
In vivo animal studies for TP-0427736 HCl typically involve administration to mice via oral gavage or intraperitoneal injection at doses determined from preliminary studies. Hair follicle growth phase prolongation is assessed in mouse models. Fibrosis models, tumor xenograft models, or other TGF-β-related disease models could be used to evaluate efficacy. Tissue samples are collected for histological and biochemical analysis. The compound's pharmacokinetics and pharmacodynamics are evaluated in these models.
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| ADME/Pharmacokinetics |
TP-0427736 HCl has a molecular weight of 334.85 g/mol and formula C14H11ClN4S2. Purity is >98%. Recommended storage is powder at -20°C for 3 years and in solvent at -20°C for 6 months. The compound is soluble in DMSO and other organic solvents. Detailed PK parameters such as half-life, Cmax, AUC, and bioavailability would require experimental determination.
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| Toxicity/Toxicokinetics |
TP-0427736 HCl is intended for research use only and is not approved for human therapeutic applications. As a TGF-β signaling inhibitor, the compound may affect normal physiological processes regulated by TGF-β, which could contribute to potential toxicity. Standard preclinical toxicity assessments would include acute toxicity studies in rodents, repeated-dose toxicity studies, and assessment of off-target effects. Appropriate safety precautions should be taken when handling.
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| References | |
| Additional Infomation |
TP-0427736 HCl (CAS 2459963-17-6) is a potent ALK5 kinase inhibitor with an IC50 of 2.72 nM, showing 300-fold selectivity over ALK3 (IC50 = 836 nM). It has a molecular weight of 334.85 g/mol and formula C14H11ClN4S2. TP-0427736 HCl inhibits TGF-β1-induced Smad2/3 phosphorylation in A549 cells (IC50 = 8.68 nM) and prolongs the hair follicle growth phase in mice. It is also known as TP0427736 hydrochloride and TP-427736.
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| Molecular Formula |
C14H11CLN4S2
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|---|---|
| Molecular Weight |
334.8469
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| Exact Mass |
334.011
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| CAS # |
2459963-17-6
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| Related CAS # |
TP0427736;864374-00-5
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| PubChem CID |
137277519
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| Appearance |
Light yellow to yellow solid powder
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
21
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| Complexity |
356
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=CSC(=N1)C2=C(N=CN2)C3=CC4=C(C=C3)N=CS4.Cl
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| InChi Key |
DBKPLYNIVZJPCU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C14H10N4S2.ClH/c1-8-5-19-14(18-8)13-12(15-6-16-13)9-2-3-10-11(4-9)20-7-17-10;/h2-7H,1H3,(H,15,16);1H
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| Chemical Name |
6-[5-(4-methyl-1,3-thiazol-2-yl)-1H-imidazol-4-yl]-1,3-benzothiazole;hydrochloride
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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) |
H2O : ~3.33 mg/mL (~9.94 mM)
DMSO : ~2 mg/mL (~5.97 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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9864 mL | 14.9321 mL | 29.8641 mL | |
| 5 mM | 0.5973 mL | 2.9864 mL | 5.9728 mL | |
| 10 mM | 0.2986 mL | 1.4932 mL | 2.9864 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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