1099644-42-4
1099644-42-4 structure
- Name: ITD-1
- Chemical Name: Quizartinib
- CAS Number: 1099644-42-4
- Molecular Formula: C27H29NO3
- Molecular Weight: 415.52
- Catalog: Signaling Pathways TGF-beta/Smad TGF-β Receptor
- Create Date: 2018-03-01 04:14:15
- Modify Date: 2024-01-06 18:20:41
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ITD-1 is the first selective TGFβ inhibitor with an IC50 of 460 nM.
| Name | Quizartinib |
|---|---|
| Synonyms |
1-[5-(2-Methyl-2-propanyl)-1,2-oxazol-3-yl]-3-(4-{7-[2-(4-morpholinyl)ethoxy]imidazo[2,1-b][1,3]benzothiazol-2-yl}phenyl)urea
Quizartinib Urea, N-[5-(1,1-dimethylethyl)-3-isoxazolyl]-N'-[4-[7-[2-(4-morpholinyl)ethoxy]imidazo[2,1-b]benzothiazol-2-yl]phenyl]- ITD-1 |
| Description | ITD-1 is the first selective TGFβ inhibitor with an IC50 of 460 nM. |
|---|---|
| Related Catalog | |
| Target |
IC50: 460 nM (TGFβ) |
| In Vitro | ITD-1 potently blocks phosphorylation of the effector SMAD2/3 proteins induced by TGFβ2, and only minimally in response to Activin A. HEK293T cells are transfected with a Smad4 response element driving luciferase (SBE4-Luc) to test whether ITD-1 blocks Activin A/Nodal and/or TGFβ signaling, which utilize the same intracellular signaling cascade through Smad4. ITD-1 strongly inhibits TGFβ2 signaling with similar efficacy (92% vs. 99% respectively), but with lower potency compared to SB-431542, an ACVR1B/TGFBR1 kinase inhibitor (IC50= 850nM vs. 70nM respectively), and is a weak and partial inhibitor of Activin A signals. ITD-1 selectively enhances the differentiation of uncommitted mesoderm to cardiomyocytes, but not to vascular smooth muscle and endothelial cells. ITD-1 reveals an unexpected role for TGFβ signaling in controlling cardiomyocyte differentiation from multipotent cardiovascular precursors. |
| Cell Assay | For the Smad4-Response element (SBE4) assay, 293T cells are grown in Phenol Free DMEM-high glucose supplemented with 1% FBS. About 30000 cells/cm2 are reverse transfected onto white 384-well cell-culture plates with 10ng of SBE4-Lux and CMV-Renilla-Lux using Lipofectamine 2000. Cells are allowed to adhere for at least 12 hours and induced with either TGFβ2 (15 ng/mL), Activin A (15 ng/mL). Simultaneously, ITD-1 (0.001, 0.01, 0.1, 1, and 10 μM) is added to cells. SB-431542 is used as a positive control for Activin A/TGFβ-signaling inhibition. To determine luminescence levels, Dual-Glo kit is used and measured on an Envision plate reader. Firefly luminescence is normalized against renilla luciferase. |
| References |
| Density | 1.4±0.1 g/cm3 |
|---|---|
| Molecular Formula | C27H29NO3 |
| Molecular Weight | 415.52 |
| LogP | 4.03 |
| Index of Refraction | 1.691 |
| Storage condition | 2-8℃ |