ITD-1 is a selective inhibitor of TGF-β signaling (IC50 = 0.85 μM); exhibits little or no inhibition of activin, Wnt or BMP signaling pathways. ITD-1 selectively enhanced the differentiation of uncommitted mesoderm to cardiomyocytes, but not to vascular smooth muscle and endothelial cells. ITD-1 is a highly selective TGF-β inhibitor and reveals an unexpected role for TGF-β signaling in controlling cardiomyocyte differentiation from multipotent cardiovascular precursors. References:
Physicochemical Properties
| Molecular Formula | C27H29NO3 |
| Molecular Weight | 415.52 |
| Exact Mass | 415.214 |
| CAS # | 1099644-42-4 |
| Related CAS # | 1099644-42-4 |
| PubChem CID | 44135961 |
| Appearance | Light yellow to yellow solid powder |
| Density | 1.4±0.1 g/cm3 |
| Index of Refraction | 1.691 |
| LogP | 4.03 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 5 |
| Heavy Atom Count | 31 |
| Complexity | 776 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | ULFUJLFTRWWLPO-UHFFFAOYSA-N |
| 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 |
| Chemical Name | ethyl 4-([1,1'-biphenyl]-4-yl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate |
| Synonyms | ITD1 ITD 1 ITD-1. |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| 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]. |
| References |
[1]. Small molecule-mediated TGF-β type II receptor degradation promotes cardiomyogenesis in embryonic stem cells. Cell Stem Cell. 2012 Aug 3;11(2):242-52. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~28 mg/mL (~67.39 mM) |
| 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 |