| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Targets |
ITD-1 targets the TGFβ type II receptor (TβRII) and induces its degradation. It inhibits TGFβ2 signaling with high efficacy (92%). It blocks Smad and MAPK activation. It has little or no inhibition of activin, Wnt, or BMP signaling pathways.
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| ln Vitro |
To find out if ITD-1 blocks Activin A/Nodal and/or TGFβ signaling, which use the same intracellular signaling cascade through Smad4, HEK293T cells were transfected with a Smad4 response element driving luciferase (SBE4-Luc). ITD-1 effectively blocks the phosphorylation of effector SMAD2/3 proteins induced by TGFβ2, with only a minimal response to Activin A. ITD-1 is an activin A weakening of the signal and partial adapters that suppresses TGFβ2 signaling with a similar efficacy (92% vs. 99%, respectively), however less potent than the ACVR1B/TGFBR1 alternative SB-431542 (IC50= 850 nM vs. 70 nM). ITD-1 preferentially increases secretion to cardiomyocytes from undefinable mesoderm, but not to endothelial cells or vascular smooth muscle. The function of TGFβ signaling in regulating the production of cardiomyocytes from multipotent cardiovascular progenitor cells is revealed by ITD-1 [1].
ITD-1 inhibits calcium transients in mouse HL-1 cells and inhibits Activin receptor and TGBR2 signaling in activin A-stimulated human HEK293T cells. It promotes the differentiation of uncommitted mesoderm into cardiomyocytes. Its IC50 is 0.4–0.8 µM for intracellular signaling. |
| ln Vivo |
ITD-1 is used to study the role of TGFβ signaling in development and disease. By inhibiting TGFβ, it promotes cardiomyocyte fate in embryonic stem cell differentiation models. Its selective inhibition of TGFβ signaling makes it a valuable tool for studying this pathway in vivo.
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| Enzyme Assay |
The in vitro activity of ITD-1 is assessed in enzyme assays measuring its ability to inhibit TGFβ receptor kinase activity. This involves using purified TβRI or TβRII kinase domains and measuring their ability to phosphorylate a substrate in the presence of the compound. IC50 values are determined.
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| Cell Assay |
In vitro cellular assays for ITD-1 involve treating cells with the compound and measuring its effect on TGFβ-induced Smad2/3 phosphorylation. This is typically done by Western blot. Its effect on target gene expression is measured by qPCR or reporter gene assays. Its ability to promote cardiomyocyte differentiation is assessed in ESC cultures.
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| Animal Protocol |
In vivo animal models for ITD-1 are not detailed in the provided sources. As a research tool, it is likely used in zebrafish or mouse models to study the role of TGFβ signaling in development and tissue regeneration. Its effects on cardiac differentiation and repair would be of particular interest.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic data for ITD-1 is not provided. It is a small molecule with a molecular weight of 408.5 g/mol. Its properties as a research compound are established for in vitro and potentially in vivo use. Its solubility and stability are characterized for laboratory use.
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| Toxicity/Toxicokinetics |
Toxicological data for ITD-1 is not detailed in the provided sources. As a research compound, it is not intended for human use. Standard safety precautions should be followed when handling. Its safety profile would need to be established for therapeutic applications.
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| References | |
| Additional Infomation |
ITD-1 is a first-in-class selective inhibitor of TGFβ signaling. It is a valuable tool for studying the role of TGFβ in stem cell biology, development, and disease. Its ability to promote cardiomyocyte differentiation makes it a promising compound for cardiac regeneration research.
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| Molecular Formula |
C27H29NO3
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|---|---|
| Molecular Weight |
415.52
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| Exact Mass |
415.214
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| CAS # |
1099644-42-4
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| Related CAS # |
1099644-42-4
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| PubChem CID |
44135961
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.4±0.1 g/cm3
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| Index of Refraction |
1.691
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| LogP |
4.03
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
31
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| Complexity |
776
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCOC(=O)C1=C(NC2=C(C1C3=CC=C(C=C3)C4=CC=CC=C4)C(=O)CC(C2)(C)C)C
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| InChi Key |
ULFUJLFTRWWLPO-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C27H29NO3/c1-5-31-26(30)23-17(2)28-21-15-27(3,4)16-22(29)25(21)24(23)20-13-11-19(12-14-20)18-9-7-6-8-10-18/h6-14,24,28H,5,15-16H2,1-4H3
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| Chemical Name |
ethyl 4-([1,1'-biphenyl]-4-yl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate
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| Synonyms |
ITD1 ITD 1 ITD-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) |
DMSO : ~28 mg/mL (~67.39 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.02 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 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 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL 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: ≥ 2.5 mg/mL (6.02 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 25.0 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 | 2.4066 mL | 12.0331 mL | 24.0662 mL | |
| 5 mM | 0.4813 mL | 2.4066 mL | 4.8132 mL | |
| 10 mM | 0.2407 mL | 1.2033 mL | 2.4066 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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